3-Benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one suppresses FcεRI-mediated mast cell degranulation via the inhibition of mTORC2-Akt signaling.
Identifieur interne : 000174 ( Main/Corpus ); précédent : 000173; suivant : 0001753-Benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one suppresses FcεRI-mediated mast cell degranulation via the inhibition of mTORC2-Akt signaling.
Auteurs : Valeriya Rakhmanova ; Sukyoung Park ; Sungwook Lee ; Young Hyo Kim ; Jinwook ShinSource :
- Biochemical and biophysical research communications [ 1090-2104 ] ; 2020.
English descriptors
- KwdEn :
- 4-Butyrolactone (analogs & derivatives), 4-Butyrolactone (pharmacology), Animals (MeSH), Cell Degranulation (drug effects), Mast Cells (drug effects), Mast Cells (immunology), Mechanistic Target of Rapamycin Complex 2 (antagonists & inhibitors), Mechanistic Target of Rapamycin Complex 2 (immunology), Mice (MeSH), Mice, Inbred C57BL (MeSH), Proto-Oncogene Proteins c-akt (antagonists & inhibitors), Proto-Oncogene Proteins c-akt (immunology), Receptors, IgE (antagonists & inhibitors), Receptors, IgE (immunology), Signal Transduction (drug effects), Signal Transduction (immunology).
- MESH :
- chemical , analogs & derivatives : 4-Butyrolactone.
- chemical , antagonists & inhibitors : Mechanistic Target of Rapamycin Complex 2, Proto-Oncogene Proteins c-akt, Receptors, IgE.
- chemical , immunology : Mechanistic Target of Rapamycin Complex 2, Proto-Oncogene Proteins c-akt, Receptors, IgE.
- chemical , pharmacology : 4-Butyrolactone.
- drug effects : Cell Degranulation, Mast Cells, Signal Transduction.
- immunology : Mast Cells, Signal Transduction.
- Animals, Mice, Mice, Inbred C57BL.
Abstract
Mast cells express high-affinity IgE receptor (FcεRI) on their surface, cross-linking of which leads to the immediate release of proinflammatory mediators such as histamine but also late-phase cytokine secretion, which are central to the pathogenesis of allergic diseases. Despite the growing evidences that mammalian target of rapamycin (mTOR) plays important roles in the immune system, it is still unclear how mTOR signaling regulates mast cell function. In this study, we investigated the effects of 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO) as an mTOR agonist on FcεRI-mediated allergic responses of mast cells. Our data showed that administration of 3BDO decreased β-hexosaminidase, interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) release in murine bone marrow-derived mast cells (BMMCs) after FcεRI cross-linking, which was associated with an increase in mTOR complex 1 (mTORC1) signaling but a decrease in activation of Erk1/2, Jnk, and mTORC2-Akt. In addition, we found that a specific Akt agonist, SC79, is able to fully restore the decrease of β-hexosaminidase release in 3BDO-treated BMMCs but has no effect on IL-6 release in these cells, suggesting that 3BDO negatively regulates FcεRI-mediated degranulation and cytokine release through differential mechanisms in mast cells. The present data demonstrate that proper activation of mTORC1 is crucial for mast cell effector function, suggesting the applicability of the mTORC1 activator as a useful therapeutic agent in mast cell-related diseases.
DOI: 10.1016/j.bbrc.2019.10.075
PubMed: 31629474
Links to Exploration step
pubmed:31629474Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">3-Benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one suppresses FcεRI-mediated mast cell degranulation via the inhibition of mTORC2-Akt signaling.</title><author><name sortKey="Rakhmanova, Valeriya" sort="Rakhmanova, Valeriya" uniqKey="Rakhmanova V" first="Valeriya" last="Rakhmanova">Valeriya Rakhmanova</name><affiliation><nlm:affiliation>Department of Microbiology, Inha University School of Medicine, Incheon, 22212, South Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Park, Sukyoung" sort="Park, Sukyoung" uniqKey="Park S" first="Sukyoung" last="Park">Sukyoung Park</name><affiliation><nlm:affiliation>Department of Microbiology, Inha University School of Medicine, Incheon, 22212, South Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Lee, Sungwook" sort="Lee, Sungwook" uniqKey="Lee S" first="Sungwook" last="Lee">Sungwook Lee</name><affiliation><nlm:affiliation>Division of Tumor Immunology, National Cancer Center, Goyang, 10408, South Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Young Hyo" sort="Kim, Young Hyo" uniqKey="Kim Y" first="Young Hyo" last="Kim">Young Hyo Kim</name><affiliation><nlm:affiliation>Department of Otorhinolaryngology-Head and Neck Surgery, Inha University School of Medicine, Incheon, 22212, South Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Shin, Jinwook" sort="Shin, Jinwook" uniqKey="Shin J" first="Jinwook" last="Shin">Jinwook Shin</name><affiliation><nlm:affiliation>Department of Microbiology, Inha University School of Medicine, Incheon, 22212, South Korea. Electronic address: shin001@inha.ac.kr.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:31629474</idno><idno type="pmid">31629474</idno><idno type="doi">10.1016/j.bbrc.2019.10.075</idno><idno type="wicri:Area/Main/Corpus">000174</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000174</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">3-Benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one suppresses FcεRI-mediated mast cell degranulation via the inhibition of mTORC2-Akt signaling.</title><author><name sortKey="Rakhmanova, Valeriya" sort="Rakhmanova, Valeriya" uniqKey="Rakhmanova V" first="Valeriya" last="Rakhmanova">Valeriya Rakhmanova</name><affiliation><nlm:affiliation>Department of Microbiology, Inha University School of Medicine, Incheon, 22212, South Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Park, Sukyoung" sort="Park, Sukyoung" uniqKey="Park S" first="Sukyoung" last="Park">Sukyoung Park</name><affiliation><nlm:affiliation>Department of Microbiology, Inha University School of Medicine, Incheon, 22212, South Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Lee, Sungwook" sort="Lee, Sungwook" uniqKey="Lee S" first="Sungwook" last="Lee">Sungwook Lee</name><affiliation><nlm:affiliation>Division of Tumor Immunology, National Cancer Center, Goyang, 10408, South Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Young Hyo" sort="Kim, Young Hyo" uniqKey="Kim Y" first="Young Hyo" last="Kim">Young Hyo Kim</name><affiliation><nlm:affiliation>Department of Otorhinolaryngology-Head and Neck Surgery, Inha University School of Medicine, Incheon, 22212, South Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Shin, Jinwook" sort="Shin, Jinwook" uniqKey="Shin J" first="Jinwook" last="Shin">Jinwook Shin</name><affiliation><nlm:affiliation>Department of Microbiology, Inha University School of Medicine, Incheon, 22212, South Korea. Electronic address: shin001@inha.ac.kr.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Biochemical and biophysical research communications</title><idno type="eISSN">1090-2104</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>4-Butyrolactone (analogs & derivatives)</term><term>4-Butyrolactone (pharmacology)</term><term>Animals (MeSH)</term><term>Cell Degranulation (drug effects)</term><term>Mast Cells (drug effects)</term><term>Mast Cells (immunology)</term><term>Mechanistic Target of Rapamycin Complex 2 (antagonists & inhibitors)</term><term>Mechanistic Target of Rapamycin Complex 2 (immunology)</term><term>Mice (MeSH)</term><term>Mice, Inbred C57BL (MeSH)</term><term>Proto-Oncogene Proteins c-akt (antagonists & inhibitors)</term><term>Proto-Oncogene Proteins c-akt (immunology)</term><term>Receptors, IgE (antagonists & inhibitors)</term><term>Receptors, IgE (immunology)</term><term>Signal Transduction (drug effects)</term><term>Signal Transduction (immunology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>4-Butyrolactone</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Mechanistic Target of Rapamycin Complex 2</term><term>Proto-Oncogene Proteins c-akt</term><term>Receptors, IgE</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Mechanistic Target of Rapamycin Complex 2</term><term>Proto-Oncogene Proteins c-akt</term><term>Receptors, IgE</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>4-Butyrolactone</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Degranulation</term><term>Mast Cells</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Mast Cells</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Mice</term><term>Mice, Inbred C57BL</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mast cells express high-affinity IgE receptor (FcεRI) on their surface, cross-linking of which leads to the immediate release of proinflammatory mediators such as histamine but also late-phase cytokine secretion, which are central to the pathogenesis of allergic diseases. Despite the growing evidences that mammalian target of rapamycin (mTOR) plays important roles in the immune system, it is still unclear how mTOR signaling regulates mast cell function. In this study, we investigated the effects of 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO) as an mTOR agonist on FcεRI-mediated allergic responses of mast cells. Our data showed that administration of 3BDO decreased β-hexosaminidase, interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) release in murine bone marrow-derived mast cells (BMMCs) after FcεRI cross-linking, which was associated with an increase in mTOR complex 1 (mTORC1) signaling but a decrease in activation of Erk1/2, Jnk, and mTORC2-Akt. In addition, we found that a specific Akt agonist, SC79, is able to fully restore the decrease of β-hexosaminidase release in 3BDO-treated BMMCs but has no effect on IL-6 release in these cells, suggesting that 3BDO negatively regulates FcεRI-mediated degranulation and cytokine release through differential mechanisms in mast cells. The present data demonstrate that proper activation of mTORC1 is crucial for mast cell effector function, suggesting the applicability of the mTORC1 activator as a useful therapeutic agent in mast cell-related diseases.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31629474</PMID><DateCompleted><Year>2020</Year><Month>07</Month><Day>06</Day></DateCompleted><DateRevised><Year>2020</Year><Month>07</Month><Day>06</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1090-2104</ISSN><JournalIssue CitedMedium="Internet"><Volume>521</Volume><Issue>1</Issue><PubDate><Year>2020</Year><Month>01</Month><Day>01</Day></PubDate></JournalIssue><Title>Biochemical and biophysical research communications</Title><ISOAbbreviation>Biochem Biophys Res Commun</ISOAbbreviation></Journal><ArticleTitle>3-Benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one suppresses FcεRI-mediated mast cell degranulation via the inhibition of mTORC2-Akt signaling.</ArticleTitle><Pagination><MedlinePgn>72-76</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0006-291X(19)31968-0</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.bbrc.2019.10.075</ELocationID><Abstract><AbstractText>Mast cells express high-affinity IgE receptor (FcεRI) on their surface, cross-linking of which leads to the immediate release of proinflammatory mediators such as histamine but also late-phase cytokine secretion, which are central to the pathogenesis of allergic diseases. Despite the growing evidences that mammalian target of rapamycin (mTOR) plays important roles in the immune system, it is still unclear how mTOR signaling regulates mast cell function. In this study, we investigated the effects of 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO) as an mTOR agonist on FcεRI-mediated allergic responses of mast cells. Our data showed that administration of 3BDO decreased β-hexosaminidase, interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) release in murine bone marrow-derived mast cells (BMMCs) after FcεRI cross-linking, which was associated with an increase in mTOR complex 1 (mTORC1) signaling but a decrease in activation of Erk1/2, Jnk, and mTORC2-Akt. In addition, we found that a specific Akt agonist, SC79, is able to fully restore the decrease of β-hexosaminidase release in 3BDO-treated BMMCs but has no effect on IL-6 release in these cells, suggesting that 3BDO negatively regulates FcεRI-mediated degranulation and cytokine release through differential mechanisms in mast cells. The present data demonstrate that proper activation of mTORC1 is crucial for mast cell effector function, suggesting the applicability of the mTORC1 activator as a useful therapeutic agent in mast cell-related diseases.</AbstractText><CopyrightInformation>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rakhmanova</LastName><ForeName>Valeriya</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Inha University School of Medicine, Incheon, 22212, South Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Park</LastName><ForeName>Sukyoung</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Inha University School of Medicine, Incheon, 22212, South Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Sungwook</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Tumor Immunology, National Cancer Center, Goyang, 10408, South Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Young Hyo</ForeName><Initials>YH</Initials><AffiliationInfo><Affiliation>Department of Otorhinolaryngology-Head and Neck Surgery, Inha University School of Medicine, Incheon, 22212, South Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shin</LastName><ForeName>Jinwook</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Inha University School of Medicine, Incheon, 22212, South Korea. Electronic address: shin001@inha.ac.kr.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>10</Month><Day>16</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Biochem Biophys Res Commun</MedlineTA><NlmUniqueID>0372516</NlmUniqueID><ISSNLinking>0006-291X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C553471">3-benzyl-5-((2-nitrophenoxy)methyl)dihydrofuran-2(3H)-one</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D017455">Receptors, IgE</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000076225">Mechanistic Target of Rapamycin Complex 2</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D051057">Proto-Oncogene Proteins c-akt</NameOfSubstance></Chemical><Chemical><RegistryNumber>OL659KIY4X</RegistryNumber><NameOfSubstance UI="D015107">4-Butyrolactone</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D015107" MajorTopicYN="N">4-Butyrolactone</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="Y">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015550" MajorTopicYN="N">Cell Degranulation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008407" MajorTopicYN="N">Mast Cells</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000076225" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 2</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051057" MajorTopicYN="N">Proto-Oncogene Proteins c-akt</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017455" MajorTopicYN="N">Receptors, IgE</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">3BDO</Keyword><Keyword MajorTopicYN="Y">Activation</Keyword><Keyword MajorTopicYN="Y">Akt</Keyword><Keyword MajorTopicYN="Y">Mast cells</Keyword><Keyword MajorTopicYN="Y">mTOR</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>09</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>10</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>10</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>7</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>10</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31629474</ArticleId><ArticleId IdType="pii">S0006-291X(19)31968-0</ArticleId><ArticleId IdType="doi">10.1016/j.bbrc.2019.10.075</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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