Anti-inflammatory effect of lovastatin is mediated via the modulation of NF-κB and inhibition of HDAC1 and the PI3K/Akt/mTOR pathway in RAW264.7 macrophages.
Identifieur interne : 000658 ( Main/Exploration ); précédent : 000657; suivant : 000659Anti-inflammatory effect of lovastatin is mediated via the modulation of NF-κB and inhibition of HDAC1 and the PI3K/Akt/mTOR pathway in RAW264.7 macrophages.
Auteurs : Hyung-Wook Choi [Corée du Sud] ; Pyung-Gyun Shin [Corée du Sud] ; Ji-Hyun Lee [Corée du Sud] ; Woo-Suk Choi [États-Unis] ; Min-Jae Kang [Corée du Sud] ; Won-Sik Kong [Corée du Sud] ; Min-Ji Oh [Corée du Sud] ; Yong-Bae Seo [Corée du Sud] ; Gun-Do Kim [Corée du Sud]Source :
- International journal of molecular medicine [ 1791-244X ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Anti-inflammatoires (administration et posologie), Cellules RAW 264.7 (MeSH), Facteur de nécrose tumorale alpha (génétique), Facteur de transcription NF-kappa B (génétique), Histone Deacetylase 1 (antagonistes et inhibiteurs), Histone Deacetylase 1 (génétique), Humains (MeSH), Inflammation (anatomopathologie), Inflammation (génétique), Inflammation (induit chimiquement), Inflammation (traitement médicamenteux), Lipopolysaccharides (toxicité), Lovastatine (administration et posologie), Macrophages (anatomopathologie), Macrophages (effets des médicaments et des substances chimiques), Nitric oxide synthase type II (génétique), Phosphatidylinositol 3-kinases (génétique), Protéines proto-oncogènes c-akt (génétique), Régulation de l'expression des gènes (effets des médicaments et des substances chimiques), Souris (MeSH), Sérine-thréonine kinases TOR (génétique).
- MESH :
- administration et posologie : Anti-inflammatoires, Lovastatine.
- anatomopathologie : Inflammation, Macrophages.
- antagonistes et inhibiteurs : Histone Deacetylase 1.
- effets des médicaments et des substances chimiques : Macrophages, Régulation de l'expression des gènes.
- génétique : Facteur de nécrose tumorale alpha, Facteur de transcription NF-kappa B, Histone Deacetylase 1, Inflammation, Nitric oxide synthase type II, Phosphatidylinositol 3-kinases, Protéines proto-oncogènes c-akt, Sérine-thréonine kinases TOR.
- induit chimiquement : Inflammation.
- toxicité : Lipopolysaccharides.
- traitement médicamenteux : Inflammation.
- Animaux, Cellules RAW 264.7, Humains, Souris.
English descriptors
- KwdEn :
- Animals (MeSH), Anti-Inflammatory Agents (administration & dosage), Gene Expression Regulation (drug effects), Histone Deacetylase 1 (antagonists & inhibitors), Histone Deacetylase 1 (genetics), Humans (MeSH), Inflammation (chemically induced), Inflammation (drug therapy), Inflammation (genetics), Inflammation (pathology), Lipopolysaccharides (toxicity), Lovastatin (administration & dosage), Macrophages (drug effects), Macrophages (pathology), Mice (MeSH), NF-kappa B (genetics), Nitric Oxide Synthase Type II (genetics), Phosphatidylinositol 3-Kinases (genetics), Proto-Oncogene Proteins c-akt (genetics), RAW 264.7 Cells (MeSH), TOR Serine-Threonine Kinases (genetics), Tumor Necrosis Factor-alpha (genetics).
- MESH :
- chemical , administration & dosage : Anti-Inflammatory Agents, Lovastatin.
- chemical , antagonists & inhibitors : Histone Deacetylase 1.
- chemically induced : Inflammation.
- drug effects : Gene Expression Regulation, Macrophages.
- drug therapy : Inflammation.
- chemical , genetics : Histone Deacetylase 1, Inflammation, NF-kappa B, Nitric Oxide Synthase Type II, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases, Tumor Necrosis Factor-alpha.
- pathology : Inflammation, Macrophages.
- chemical , toxicity : Lipopolysaccharides.
- Animals, Humans, Mice, RAW 264.7 Cells.
Abstract
Lovastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor that is clinically used for the prevention of cardiovascular diseases. Although it has been reported that lovastatin has anti-inflammatory properties in several studies, how lovastatin regulates the inflammation is still unclear. To evaluate the effect of lovastatin on nitric oxide production (NO) in RAW264.7 macrophages, NO production assay was performed. Also, cell viability was measured to confirm cytotoxicity. Level of tumor necrosis factor-α (TNF-α) transcription was measured by reverse transcription polymerase chain reaction (RT-PCR) from total RNA in RAW264.7 cells. Western blot analysis and immunofluorescence staining were used to investigate the regulation of lovastatin on the expression, phosphorylation, and nuclear translocation of cellular proteins. The results of the present study revealed that lovastatin reduced nitric oxide production via the reduction of inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. The mRNA level of TNF-α was reduced in presence of lovastatin. In addition, lovastatin downregulated histone deacetylase 1 (HDAC1), resulting in the accumulation of acetylated histone H3 and heat shock protein 70. Furthermore, the expression of phosphoinositide 3-kinase catalytic subunits α and β was reduced under lovastatin treatment, and the phosphorylation of Akt and mammalian target of rapamycin was consequently inhibited. Lovastatin also inhibited the phosphorylation of inhibitor of nuclear factor (NF)-κBα and the translocation of NF-κB into the nucleus. Therefore, the present study demonstrates that lovastatin inhibits the expression of pro-inflammatory mediators, including iNOS and TNF-α, through the suppression of HDAC1 expression, PI3K/Akt phosphorylation and NF-κB translocation in LPS-stimulated RAW264.7 macrophage cells.
DOI: 10.3892/ijmm.2017.3309
PubMed: 29207042
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Anti-inflammatory effect of lovastatin is mediated via the modulation of NF-κB and inhibition of HDAC1 and the PI3K/Akt/mTOR pathway in RAW264.7 macrophages.</title><author><name sortKey="Choi, Hyung Wook" sort="Choi, Hyung Wook" uniqKey="Choi H" first="Hyung-Wook" last="Choi">Hyung-Wook Choi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, Pukyong National University, Busan 48513</wicri:regionArea><wicri:noRegion>Busan 48513</wicri:noRegion></affiliation></author><author><name sortKey="Shin, Pyung Gyun" sort="Shin, Pyung Gyun" uniqKey="Shin P" first="Pyung-Gyun" last="Shin">Pyung-Gyun Shin</name><affiliation wicri:level="1"><nlm:affiliation>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709</wicri:regionArea><wicri:noRegion>Eumseong 27709</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Ji Hyun" sort="Lee, Ji Hyun" uniqKey="Lee J" first="Ji-Hyun" last="Lee">Ji-Hyun Lee</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, Pukyong National University, Busan 48513</wicri:regionArea><wicri:noRegion>Busan 48513</wicri:noRegion></affiliation></author><author><name sortKey="Choi, Woo Suk" sort="Choi, Woo Suk" uniqKey="Choi W" first="Woo-Suk" last="Choi">Woo-Suk Choi</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61802</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Kang, Min Jae" sort="Kang, Min Jae" uniqKey="Kang M" first="Min-Jae" last="Kang">Min-Jae Kang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, Pukyong National University, Busan 48513</wicri:regionArea><wicri:noRegion>Busan 48513</wicri:noRegion></affiliation></author><author><name sortKey="Kong, Won Sik" sort="Kong, Won Sik" uniqKey="Kong W" first="Won-Sik" last="Kong">Won-Sik Kong</name><affiliation wicri:level="1"><nlm:affiliation>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709</wicri:regionArea><wicri:noRegion>Eumseong 27709</wicri:noRegion></affiliation></author><author><name sortKey="Oh, Min Ji" sort="Oh, Min Ji" uniqKey="Oh M" first="Min-Ji" last="Oh">Min-Ji Oh</name><affiliation wicri:level="1"><nlm:affiliation>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709</wicri:regionArea><wicri:noRegion>Eumseong 27709</wicri:noRegion></affiliation></author><author><name sortKey="Seo, Yong Bae" sort="Seo, Yong Bae" uniqKey="Seo Y" first="Yong-Bae" last="Seo">Yong-Bae Seo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, Pukyong National University, Busan 48513</wicri:regionArea><wicri:noRegion>Busan 48513</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Gun Do" sort="Kim, Gun Do" uniqKey="Kim G" first="Gun-Do" last="Kim">Gun-Do Kim</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, Pukyong National University, Busan 48513</wicri:regionArea><wicri:noRegion>Busan 48513</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2018">2018</date><idno type="RBID">pubmed:29207042</idno><idno type="pmid">29207042</idno><idno type="doi">10.3892/ijmm.2017.3309</idno><idno type="wicri:Area/Main/Corpus">000659</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000659</idno><idno type="wicri:Area/Main/Curation">000659</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000659</idno><idno type="wicri:Area/Main/Exploration">000659</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Anti-inflammatory effect of lovastatin is mediated via the modulation of NF-κB and inhibition of HDAC1 and the PI3K/Akt/mTOR pathway in RAW264.7 macrophages.</title><author><name sortKey="Choi, Hyung Wook" sort="Choi, Hyung Wook" uniqKey="Choi H" first="Hyung-Wook" last="Choi">Hyung-Wook Choi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, Pukyong National University, Busan 48513</wicri:regionArea><wicri:noRegion>Busan 48513</wicri:noRegion></affiliation></author><author><name sortKey="Shin, Pyung Gyun" sort="Shin, Pyung Gyun" uniqKey="Shin P" first="Pyung-Gyun" last="Shin">Pyung-Gyun Shin</name><affiliation wicri:level="1"><nlm:affiliation>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709</wicri:regionArea><wicri:noRegion>Eumseong 27709</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Ji Hyun" sort="Lee, Ji Hyun" uniqKey="Lee J" first="Ji-Hyun" last="Lee">Ji-Hyun Lee</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, Pukyong National University, Busan 48513</wicri:regionArea><wicri:noRegion>Busan 48513</wicri:noRegion></affiliation></author><author><name sortKey="Choi, Woo Suk" sort="Choi, Woo Suk" uniqKey="Choi W" first="Woo-Suk" last="Choi">Woo-Suk Choi</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61802</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Kang, Min Jae" sort="Kang, Min Jae" uniqKey="Kang M" first="Min-Jae" last="Kang">Min-Jae Kang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, Pukyong National University, Busan 48513</wicri:regionArea><wicri:noRegion>Busan 48513</wicri:noRegion></affiliation></author><author><name sortKey="Kong, Won Sik" sort="Kong, Won Sik" uniqKey="Kong W" first="Won-Sik" last="Kong">Won-Sik Kong</name><affiliation wicri:level="1"><nlm:affiliation>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709</wicri:regionArea><wicri:noRegion>Eumseong 27709</wicri:noRegion></affiliation></author><author><name sortKey="Oh, Min Ji" sort="Oh, Min Ji" uniqKey="Oh M" first="Min-Ji" last="Oh">Min-Ji Oh</name><affiliation wicri:level="1"><nlm:affiliation>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709</wicri:regionArea><wicri:noRegion>Eumseong 27709</wicri:noRegion></affiliation></author><author><name sortKey="Seo, Yong Bae" sort="Seo, Yong Bae" uniqKey="Seo Y" first="Yong-Bae" last="Seo">Yong-Bae Seo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, Pukyong National University, Busan 48513</wicri:regionArea><wicri:noRegion>Busan 48513</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Gun Do" sort="Kim, Gun Do" uniqKey="Kim G" first="Gun-Do" last="Kim">Gun-Do Kim</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, Pukyong National University, Busan 48513</wicri:regionArea><wicri:noRegion>Busan 48513</wicri:noRegion></affiliation></author></analytic><series><title level="j">International journal of molecular medicine</title><idno type="eISSN">1791-244X</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Anti-Inflammatory Agents (administration & dosage)</term><term>Gene Expression Regulation (drug effects)</term><term>Histone Deacetylase 1 (antagonists & inhibitors)</term><term>Histone Deacetylase 1 (genetics)</term><term>Humans (MeSH)</term><term>Inflammation (chemically induced)</term><term>Inflammation (drug therapy)</term><term>Inflammation (genetics)</term><term>Inflammation (pathology)</term><term>Lipopolysaccharides (toxicity)</term><term>Lovastatin (administration & dosage)</term><term>Macrophages (drug effects)</term><term>Macrophages (pathology)</term><term>Mice (MeSH)</term><term>NF-kappa B (genetics)</term><term>Nitric Oxide Synthase Type II (genetics)</term><term>Phosphatidylinositol 3-Kinases (genetics)</term><term>Proto-Oncogene Proteins c-akt (genetics)</term><term>RAW 264.7 Cells (MeSH)</term><term>TOR Serine-Threonine Kinases (genetics)</term><term>Tumor Necrosis Factor-alpha (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Anti-inflammatoires (administration et posologie)</term><term>Cellules RAW 264.7 (MeSH)</term><term>Facteur de nécrose tumorale alpha (génétique)</term><term>Facteur de transcription NF-kappa B (génétique)</term><term>Histone Deacetylase 1 (antagonistes et inhibiteurs)</term><term>Histone Deacetylase 1 (génétique)</term><term>Humains (MeSH)</term><term>Inflammation (anatomopathologie)</term><term>Inflammation (génétique)</term><term>Inflammation (induit chimiquement)</term><term>Inflammation (traitement médicamenteux)</term><term>Lipopolysaccharides (toxicité)</term><term>Lovastatine (administration et posologie)</term><term>Macrophages (anatomopathologie)</term><term>Macrophages (effets des médicaments et des substances chimiques)</term><term>Nitric oxide synthase type II (génétique)</term><term>Phosphatidylinositol 3-kinases (génétique)</term><term>Protéines proto-oncogènes c-akt (génétique)</term><term>Régulation de l'expression des gènes (effets des médicaments et des substances chimiques)</term><term>Souris (MeSH)</term><term>Sérine-thréonine kinases TOR (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Anti-Inflammatory Agents</term><term>Lovastatin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Histone Deacetylase 1</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Anti-inflammatoires</term><term>Lovastatine</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Inflammation</term><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Histone Deacetylase 1</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Inflammation</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Gene Expression Regulation</term><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Inflammation</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Macrophages</term><term>Régulation de l'expression des gènes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Histone Deacetylase 1</term><term>Inflammation</term><term>NF-kappa B</term><term>Nitric Oxide Synthase Type II</term><term>Phosphatidylinositol 3-Kinases</term><term>Proto-Oncogene Proteins c-akt</term><term>TOR Serine-Threonine Kinases</term><term>Tumor Necrosis Factor-alpha</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteur de nécrose tumorale alpha</term><term>Facteur de transcription NF-kappa B</term><term>Histone Deacetylase 1</term><term>Inflammation</term><term>Nitric oxide synthase type II</term><term>Phosphatidylinositol 3-kinases</term><term>Protéines proto-oncogènes c-akt</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="induit chimiquement" xml:lang="fr"><term>Inflammation</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Inflammation</term><term>Macrophages</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Lipopolysaccharides</term></keywords><keywords scheme="MESH" qualifier="toxicité" xml:lang="fr"><term>Lipopolysaccharides</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Inflammation</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term><term>Mice</term><term>RAW 264.7 Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules RAW 264.7</term><term>Humains</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Lovastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor that is clinically used for the prevention of cardiovascular diseases. Although it has been reported that lovastatin has anti-inflammatory properties in several studies, how lovastatin regulates the inflammation is still unclear. To evaluate the effect of lovastatin on nitric oxide production (NO) in RAW264.7 macrophages, NO production assay was performed. Also, cell viability was measured to confirm cytotoxicity. Level of tumor necrosis factor-α (TNF-α) transcription was measured by reverse transcription polymerase chain reaction (RT-PCR) from total RNA in RAW264.7 cells. Western blot analysis and immunofluorescence staining were used to investigate the regulation of lovastatin on the expression, phosphorylation, and nuclear translocation of cellular proteins. The results of the present study revealed that lovastatin reduced nitric oxide production via the reduction of inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. The mRNA level of TNF-α was reduced in presence of lovastatin. In addition, lovastatin downregulated histone deacetylase 1 (HDAC1), resulting in the accumulation of acetylated histone H3 and heat shock protein 70. Furthermore, the expression of phosphoinositide 3-kinase catalytic subunits α and β was reduced under lovastatin treatment, and the phosphorylation of Akt and mammalian target of rapamycin was consequently inhibited. Lovastatin also inhibited the phosphorylation of inhibitor of nuclear factor (NF)-κBα and the translocation of NF-κB into the nucleus. Therefore, the present study demonstrates that lovastatin inhibits the expression of pro-inflammatory mediators, including iNOS and TNF-α, through the suppression of HDAC1 expression, PI3K/Akt phosphorylation and NF-κB translocation in LPS-stimulated RAW264.7 macrophage cells.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29207042</PMID><DateCompleted><Year>2018</Year><Month>07</Month><Day>17</Day></DateCompleted><DateRevised><Year>2018</Year><Month>07</Month><Day>17</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1791-244X</ISSN><JournalIssue CitedMedium="Internet"><Volume>41</Volume><Issue>2</Issue><PubDate><Year>2018</Year><Month>Feb</Month></PubDate></JournalIssue><Title>International journal of molecular medicine</Title><ISOAbbreviation>Int J Mol Med</ISOAbbreviation></Journal><ArticleTitle>Anti-inflammatory effect of lovastatin is mediated via the modulation of NF-κB and inhibition of HDAC1 and the PI3K/Akt/mTOR pathway in RAW264.7 macrophages.</ArticleTitle><Pagination><MedlinePgn>1103-1109</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3892/ijmm.2017.3309</ELocationID><Abstract><AbstractText>Lovastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor that is clinically used for the prevention of cardiovascular diseases. Although it has been reported that lovastatin has anti-inflammatory properties in several studies, how lovastatin regulates the inflammation is still unclear. To evaluate the effect of lovastatin on nitric oxide production (NO) in RAW264.7 macrophages, NO production assay was performed. Also, cell viability was measured to confirm cytotoxicity. Level of tumor necrosis factor-α (TNF-α) transcription was measured by reverse transcription polymerase chain reaction (RT-PCR) from total RNA in RAW264.7 cells. Western blot analysis and immunofluorescence staining were used to investigate the regulation of lovastatin on the expression, phosphorylation, and nuclear translocation of cellular proteins. The results of the present study revealed that lovastatin reduced nitric oxide production via the reduction of inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. The mRNA level of TNF-α was reduced in presence of lovastatin. In addition, lovastatin downregulated histone deacetylase 1 (HDAC1), resulting in the accumulation of acetylated histone H3 and heat shock protein 70. Furthermore, the expression of phosphoinositide 3-kinase catalytic subunits α and β was reduced under lovastatin treatment, and the phosphorylation of Akt and mammalian target of rapamycin was consequently inhibited. Lovastatin also inhibited the phosphorylation of inhibitor of nuclear factor (NF)-κBα and the translocation of NF-κB into the nucleus. Therefore, the present study demonstrates that lovastatin inhibits the expression of pro-inflammatory mediators, including iNOS and TNF-α, through the suppression of HDAC1 expression, PI3K/Akt phosphorylation and NF-κB translocation in LPS-stimulated RAW264.7 macrophage cells.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Choi</LastName><ForeName>Hyung-Wook</ForeName><Initials>HW</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shin</LastName><ForeName>Pyung-Gyun</ForeName><Initials>PG</Initials><AffiliationInfo><Affiliation>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Ji-Hyun</ForeName><Initials>JH</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Choi</LastName><ForeName>Woo-Suk</ForeName><Initials>WS</Initials><AffiliationInfo><Affiliation>Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kang</LastName><ForeName>Min-Jae</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kong</LastName><ForeName>Won-Sik</ForeName><Initials>WS</Initials><AffiliationInfo><Affiliation>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oh</LastName><ForeName>Min-Ji</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Seo</LastName><ForeName>Yong-Bae</ForeName><Initials>YB</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Gun-Do</ForeName><Initials>GD</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Pukyong National University, Busan 48513, Republic of Korea.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>12</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>Greece</Country><MedlineTA>Int J Mol Med</MedlineTA><NlmUniqueID>9810955</NlmUniqueID><ISSNLinking>1107-3756</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000893">Anti-Inflammatory Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008070">Lipopolysaccharides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016328">NF-kappa B</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014409">Tumor Necrosis Factor-alpha</NameOfSubstance></Chemical><Chemical><RegistryNumber>9LHU78OQFD</RegistryNumber><NameOfSubstance UI="D008148">Lovastatin</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.13.39</RegistryNumber><NameOfSubstance UI="D052247">Nitric Oxide Synthase Type II</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.13.39</RegistryNumber><NameOfSubstance UI="C496317">Nos2 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.-</RegistryNumber><NameOfSubstance UI="D019869">Phosphatidylinositol 3-Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="C546843">mTOR protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D051057">Proto-Oncogene Proteins c-akt</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.5.1.98</RegistryNumber><NameOfSubstance UI="C484389">Hdac1 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.5.1.98</RegistryNumber><NameOfSubstance UI="D056284">Histone Deacetylase 1</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000893" MajorTopicYN="N">Anti-Inflammatory Agents</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005786" MajorTopicYN="N">Gene Expression Regulation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D056284" MajorTopicYN="N">Histone Deacetylase 1</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007249" MajorTopicYN="N">Inflammation</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008070" MajorTopicYN="N">Lipopolysaccharides</DescriptorName><QualifierName UI="Q000633" MajorTopicYN="N">toxicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008148" MajorTopicYN="N">Lovastatin</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008264" MajorTopicYN="N">Macrophages</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016328" MajorTopicYN="N">NF-kappa B</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D052247" MajorTopicYN="N">Nitric Oxide Synthase Type II</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019869" MajorTopicYN="N">Phosphatidylinositol 3-Kinases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051057" MajorTopicYN="N">Proto-Oncogene Proteins c-akt</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000067996" MajorTopicYN="N">RAW 264.7 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014409" MajorTopicYN="N">Tumor Necrosis Factor-alpha</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>01</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>11</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>12</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>7</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>12</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">29207042</ArticleId><ArticleId IdType="doi">10.3892/ijmm.2017.3309</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Corée du Sud</li><li>États-Unis</li></country><region><li>Illinois</li></region></list><tree><country name="Corée du Sud"><noRegion><name sortKey="Choi, Hyung Wook" sort="Choi, Hyung Wook" uniqKey="Choi H" first="Hyung-Wook" last="Choi">Hyung-Wook Choi</name></noRegion><name sortKey="Kang, Min Jae" sort="Kang, Min Jae" uniqKey="Kang M" first="Min-Jae" last="Kang">Min-Jae Kang</name><name sortKey="Kim, Gun Do" sort="Kim, Gun Do" uniqKey="Kim G" first="Gun-Do" last="Kim">Gun-Do Kim</name><name sortKey="Kong, Won Sik" sort="Kong, Won Sik" uniqKey="Kong W" first="Won-Sik" last="Kong">Won-Sik Kong</name><name sortKey="Lee, Ji Hyun" sort="Lee, Ji Hyun" uniqKey="Lee J" first="Ji-Hyun" last="Lee">Ji-Hyun Lee</name><name sortKey="Oh, Min Ji" sort="Oh, Min Ji" uniqKey="Oh M" first="Min-Ji" last="Oh">Min-Ji Oh</name><name sortKey="Seo, Yong Bae" sort="Seo, Yong Bae" uniqKey="Seo Y" first="Yong-Bae" last="Seo">Yong-Bae Seo</name><name sortKey="Shin, Pyung Gyun" sort="Shin, Pyung Gyun" uniqKey="Shin P" first="Pyung-Gyun" last="Shin">Pyung-Gyun Shin</name></country><country name="États-Unis"><region name="Illinois"><name sortKey="Choi, Woo Suk" sort="Choi, Woo Suk" uniqKey="Choi W" first="Woo-Suk" last="Choi">Woo-Suk Choi</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Bois/explor/RapamycinFungusV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000658 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000658 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Bois
|area= RapamycinFungusV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:29207042
|texte= Anti-inflammatory effect of lovastatin is mediated via the modulation of NF-κB and inhibition of HDAC1 and the PI3K/Akt/mTOR pathway in RAW264.7 macrophages.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:29207042" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a RapamycinFungusV1
| This area was generated with Dilib version V0.6.38. |  |