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FcεRI-HDAC3-MCP1 Signaling Axis Promotes Passive Anaphylaxis Mediated by Cellular Interactions

Identifieur interne : 000A22 ( Pmc/Curation ); précédent : 000A21; suivant : 000A23

FcεRI-HDAC3-MCP1 Signaling Axis Promotes Passive Anaphylaxis Mediated by Cellular Interactions

Auteurs : Misun Kim ; Yoojung Kwon ; Hyun Suk Jung ; Youngmi Kim ; Dooil Jeoung

Source :

RBID : PMC:6801807

Abstract

Anaphylaxis is an acute and life-threatening systemic reaction. Food, drug, aero-allergen and insect sting are known to induce anaphylaxis. Mast cells and basophils are known to mediate Immunoglobulin E (IgE)-dependent anaphylaxis, while macrophages, neutrophils and basophils mediate non IgE-dependent anaphylaxis. Histone deacetylases (HDACs) play various roles in biological processes by deacetylating histones and non-histones proteins. HDAC inhibitors can increase the acetylation of target proteins and affect various inflammatory diseases such as cancers and allergic diseases. HDAC3, a class I HDAC, is known to act as epigenetic and transcriptional regulators. It has been shown that HDAC3 can interact with the high-affinity Immunoglobulin E receptor (FcεRI), to mediate passive anaphylaxis and cellular interactions during passive anaphylaxis. Effects of HDAC3 on anaphylaxis, cellular interactions involving mast cells and macrophages during anaphylaxis, and any tumorigenic potential of cancer cells enhanced by mast cells will be discussed in this review. Roles of microRNAs that form negative feedback loops with hallmarks of anaphylaxis such as HDAC3 in anaphylaxis and cellular interactions will also be discussed. The roles of MCP1 regulated by HDAC3 in cellular interactions during anaphylaxis are discussed. Roles of exosomes in cellular interactions mediated by HDAC3 during anaphylaxis are also discussed. Thus, review might provide clues for development of drugs targeting passive anaphylaxis.


Url:
DOI: 10.3390/ijms20194964
PubMed: 31597362
PubMed Central: 6801807

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PMC:6801807

Le document en format XML

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<p>Anaphylaxis is an acute and life-threatening systemic reaction. Food, drug, aero-allergen and insect sting are known to induce anaphylaxis. Mast cells and basophils are known to mediate Immunoglobulin E (IgE)-dependent anaphylaxis, while macrophages, neutrophils and basophils mediate non IgE-dependent anaphylaxis. Histone deacetylases (HDACs) play various roles in biological processes by deacetylating histones and non-histones proteins. HDAC inhibitors can increase the acetylation of target proteins and affect various inflammatory diseases such as cancers and allergic diseases. HDAC3, a class I HDAC, is known to act as epigenetic and transcriptional regulators. It has been shown that HDAC3 can interact with the high-affinity Immunoglobulin E receptor (FcεRI), to mediate passive anaphylaxis and cellular interactions during passive anaphylaxis. Effects of HDAC3 on anaphylaxis, cellular interactions involving mast cells and macrophages during anaphylaxis, and any tumorigenic potential of cancer cells enhanced by mast cells will be discussed in this review. Roles of microRNAs that form negative feedback loops with hallmarks of anaphylaxis such as HDAC3 in anaphylaxis and cellular interactions will also be discussed. The roles of MCP1 regulated by HDAC3 in cellular interactions during anaphylaxis are discussed. Roles of exosomes in cellular interactions mediated by HDAC3 during anaphylaxis are also discussed. Thus, review might provide clues for development of drugs targeting passive anaphylaxis.</p>
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</TEI>
<pmc article-type="review-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Int J Mol Sci</journal-id>
<journal-id journal-id-type="iso-abbrev">Int J Mol Sci</journal-id>
<journal-id journal-id-type="publisher-id">ijms</journal-id>
<journal-title-group>
<journal-title>International Journal of Molecular Sciences</journal-title>
</journal-title-group>
<issn pub-type="epub">1422-0067</issn>
<publisher>
<publisher-name>MDPI</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">31597362</article-id>
<article-id pub-id-type="pmc">6801807</article-id>
<article-id pub-id-type="doi">10.3390/ijms20194964</article-id>
<article-id pub-id-type="publisher-id">ijms-20-04964</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>FcεRI-HDAC3-MCP1 Signaling Axis Promotes Passive Anaphylaxis Mediated by Cellular Interactions</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Kim</surname>
<given-names>Misun</given-names>
</name>
<xref ref-type="aff" rid="af1-ijms-20-04964">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kwon</surname>
<given-names>Yoojung</given-names>
</name>
<xref ref-type="aff" rid="af1-ijms-20-04964">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jung</surname>
<given-names>Hyun Suk</given-names>
</name>
<xref ref-type="aff" rid="af1-ijms-20-04964">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kim</surname>
<given-names>Youngmi</given-names>
</name>
<xref ref-type="aff" rid="af2-ijms-20-04964">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jeoung</surname>
<given-names>Dooil</given-names>
</name>
<xref ref-type="aff" rid="af1-ijms-20-04964">1</xref>
<xref rid="c1-ijms-20-04964" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="af1-ijms-20-04964">
<label>1</label>
Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chunchon 24341, Korea;
<email>misunjtl@naver.com</email>
(M.K.);
<email>kkwon89@kangwon.ac.kr</email>
(Y.K.);
<email>hsjung@kangwon.ac.kr</email>
(H.S.J.)</aff>
<aff id="af2-ijms-20-04964">
<label>2</label>
Institute of New Frontier Research, College of Medicine, Hallym University, Chunchon 24341, Korea;
<email>kym8389@hanmail.net</email>
</aff>
<author-notes>
<corresp id="c1-ijms-20-04964">
<label>*</label>
Correspondence:
<email>jeoungd@kangwon.ac.kr</email>
; Tel.: +82-33-250-8518</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>08</day>
<month>10</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection">
<month>10</month>
<year>2019</year>
</pub-date>
<volume>20</volume>
<issue>19</issue>
<elocation-id>4964</elocation-id>
<history>
<date date-type="received">
<day>03</day>
<month>9</month>
<year>2019</year>
</date>
<date date-type="accepted">
<day>05</day>
<month>10</month>
<year>2019</year>
</date>
</history>
<permissions>
<copyright-statement>© 2019 by the authors.</copyright-statement>
<copyright-year>2019</copyright-year>
<license license-type="open-access">
<license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
).</license-p>
</license>
</permissions>
<abstract>
<p>Anaphylaxis is an acute and life-threatening systemic reaction. Food, drug, aero-allergen and insect sting are known to induce anaphylaxis. Mast cells and basophils are known to mediate Immunoglobulin E (IgE)-dependent anaphylaxis, while macrophages, neutrophils and basophils mediate non IgE-dependent anaphylaxis. Histone deacetylases (HDACs) play various roles in biological processes by deacetylating histones and non-histones proteins. HDAC inhibitors can increase the acetylation of target proteins and affect various inflammatory diseases such as cancers and allergic diseases. HDAC3, a class I HDAC, is known to act as epigenetic and transcriptional regulators. It has been shown that HDAC3 can interact with the high-affinity Immunoglobulin E receptor (FcεRI), to mediate passive anaphylaxis and cellular interactions during passive anaphylaxis. Effects of HDAC3 on anaphylaxis, cellular interactions involving mast cells and macrophages during anaphylaxis, and any tumorigenic potential of cancer cells enhanced by mast cells will be discussed in this review. Roles of microRNAs that form negative feedback loops with hallmarks of anaphylaxis such as HDAC3 in anaphylaxis and cellular interactions will also be discussed. The roles of MCP1 regulated by HDAC3 in cellular interactions during anaphylaxis are discussed. Roles of exosomes in cellular interactions mediated by HDAC3 during anaphylaxis are also discussed. Thus, review might provide clues for development of drugs targeting passive anaphylaxis.</p>
</abstract>
<kwd-group>
<kwd>Anaphylaxis</kwd>
<kwd>cellular interactions</kwd>
<kwd>FcεRI</kwd>
<kwd>HDAC3</kwd>
<kwd>MCP1</kwd>
<kwd>miRNAs</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group>
<fig id="ijms-20-04964-f001" orientation="portrait" position="float">
<label>Figure 1</label>
<caption>
<p>The mechanisms of antibody-mediated anaphylaxis. Allergen-specific Immunoglobulin E (IgE) antibodies and FcεRI-bearing effector cells play critical roles in anaphylaxis induced when concentrations of Immunoglobulin G (IgG) antibodies are low. Mast cells and basophils mediate IgE-mediated anaphylaxis. IgE-mediated anaphylaxis involves effector molecules including prostaglandins, histamine, leukotrienes, PAF, heparin, various cytokines and enzymes. The → arrows denote positive regulation.</p>
</caption>
<graphic xlink:href="ijms-20-04964-g001"></graphic>
</fig>
<fig id="ijms-20-04964-f002" orientation="portrait" position="float">
<label>Figure 2</label>
<caption>
<p>Histone deacetylase 3 (HDAC3) binds to FcεRI and mediates a triphasic cutaneous reaction (TpCR) and passive cutaneous anaphylaxis (PCA). (
<bold>A</bold>
) In the BALB/C mouse model of TpCR and PCA, HDAC3 binds to FcεRI. HDAC3, through the interaction with rac1, leads to the tyrosine nitration of HDAC2. HDAC3 also induces ubiquitination of HDAC2 to decrease the expression of HDAC2. HDAC3 increases the expression of SP1 and C-Jun, which bind to the promoter sequences of monocyte chemoattractant protein 1 (MCP1) to increase the expression of MCP1. In the absence of allergen stimulation, HDAC2 binds to the promoter sequences of MCP1 to suppress the expression of MCP1. (
<bold>B</bold>
) Mouse recombinant MCP1 protein displays angiogenic potential based on whole mount staining employing anti-PECAM antibody (upper panel) and aortic ring formation assays (lower panel). In conclusion, FcεRI-HDAC3-MCP1 signaling mediates TpCR, PCA and angiogenesis. The ↑ arrows denotes increased expression level and → arrows denote activation of transcription and positive regulation. Hollow arrows denote positive regulation.</p>
</caption>
<graphic xlink:href="ijms-20-04964-g002"></graphic>
</fig>
<fig id="ijms-20-04964-f003" orientation="portrait" position="float">
<label>Figure 3</label>
<caption>
<p>MCP1 mediates cellular interactions in passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis (PSA) regulated by the miR-122-SOCS1 negative feedback loop. Allergen stimulation activates FcεRI signaling and increases the expression of SOCS1. HDAC3 binds to the promoter sequences of SOCS1 to increase the expression of SOCS1. Allergen stimulation decreases the expression of TGFβ1 and miR-122a-5p. In this study, TGFβ1 exerts a negative effect on allergic inflammation [
<xref rid="B7-ijms-20-04964" ref-type="bibr">7</xref>
]. MiR-122a-5p and SOCS1 form a negative feedback loop. JAK2/STA3 signaling, activated by SOCS1, is responsible for the increased production and secretion of MCP1. MCP1, through CCR2, mediates cellular interactions during anaphylaxis. MCP1 also enhances the tumorigenic and metastatic potential of melanoma cells. The → arrows denote activation of transcription and ↑ arrows denotes increased expression level/ increased characteristics. Hollow arrows denote positive regulation. Both side T-bar arrows denote cross inhibition. SOCS1, Suppressor of cytokine signaling1; JAK2, Janus kinase2; MCP1, Monocyte chemoattractant protein-1; STAT, Signal transducer and activator of transcription; HDAC3, Histone deacetylase 3; CCR2, c-c chemokine receptor type 2; PSA, Passive systemic anaphylaxis.</p>
</caption>
<graphic xlink:href="ijms-20-04964-g003"></graphic>
</fig>
<fig id="ijms-20-04964-f004" orientation="portrait" position="float">
<label>Figure 4</label>
<caption>
<p>HDAC3-miR-384 negative feedback loop regulates PCA and PSA and cellular interactions during PCA and PSA. PSA increases the expression of HDAC3 and induces the activation of FcεRI signaling. HDAC3 binds to the promoter sequences of miR-384 to decrease the expression of miR-384. TargetScan predicts miR-384 as a negative regulator of HDAC3. In the absence of allergen stimulation, miR-384 binds to the 3′UTR (untranslated region) of HDAC3 to decrease the expression of HDAC3. Thus, HDAC3 and miR-384 form a negative feedback loop. HDAC3 increases the expression of MCP1, which mediates cellular interactions and enhances the tumorigenic and metastatic potential of melanoma cells. MiR-384 negatively regulates PCA and PSA and the tumorigenic and metastatic potential of melanoma cells enhanced by PSA. Allergen-stimulated mast cells and melanoma cells promote a differentiation of M2 macrophages (TAM). M2 macrophages display a higher expression of CD163, but lower expressions of inducible nitric oxide synthase (iNOS) than M1 macrophages. Allergen-activated macrophages (M2) also activate mast cells and melanoma cells. Cellular interactions in this study were investigated by co-culture experiments. The ↑ arrows denote increased expression level/ increased characteristics and ↓ arrows denote decreased expression level. Hollow arrows denote positive regulation and T-bar arrows denote negative regulation. MCP1, Monocyte chemoattractant protein-1; HDAC3, Histone deacetylase 3; CCR2, c-c chemokine receptor type 2; PSA, Passive systemic anaphylaxis.</p>
</caption>
<graphic xlink:href="ijms-20-04964-g004"></graphic>
</fig>
<fig id="ijms-20-04964-f005" orientation="portrait" position="float">
<label>Figure 5</label>
<caption>
<p>Exosomes mediate cellular interactions during PCA and PSA. Allergen stimulation induces the interaction between FcεRI and HDAC3. The expression of p62, a selective receptor of autophagy, is increased by allergen stimulation. The expression levels of HDAC3 and MCP1 are also increased. P62 binds to the promoter sequences of miR-135-5p to decrease the expression of miR-135-5p. In the absence of allergen stimulation, miR-135-5p binds to the 3′ UTR of P62 to decrease the expression of p62. P62 is present in the exosomes of allergen-stimulated mast cells and mediates cellular interactions during PCA and PSA. P62-containig exosomes promote differentiation of M2 macrophages. M2 macrophages, activated by exosomes, display higher expressions of CD163, but a lower expression of iNOS than the M1 macrophages. P62 increases expression levels of HDAC3 and MCP1 in macrophages. P62-containing exosomes also enhance tumorigenic and metastatic potential of melanoma cells. CD63 is a surface marker of exosomes. The presence of p62 within the exosomes was confirmed by immuno-electron microscopy. Arrow indicates p62 in the exosomes. The T-bar arrows denote negative regulation and hollow arrows denote positive regulation. The ↑ arrows denote increased expression level/ increased characteristics and ↓ arrows decreased expression level.</p>
</caption>
<graphic xlink:href="ijms-20-04964-g005"></graphic>
</fig>
</floats-group>
</pmc>
</record>

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