Rapamycin attenuates Th2-driven experimental allergic conjunctivitis
Allergic conjunctivitis is mediated by eosinophilic infiltration and Th2 type immune responses. This study aims to elucidate the role of rapamycin, mTOR inhibitor, on OVA-induced experimental allergic conjunctivitis (EAC). Rapamycin administration intraperitoneally markedly reduced clinical signs, t...
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Veröffentlicht in: | Clinical immunology (Orlando, Fla.) Fla.), 2018-05, Vol.190, p.1-10 |
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description | Allergic conjunctivitis is mediated by eosinophilic infiltration and Th2 type immune responses. This study aims to elucidate the role of rapamycin, mTOR inhibitor, on OVA-induced experimental allergic conjunctivitis (EAC). Rapamycin administration intraperitoneally markedly reduced clinical signs, total and OVA-specific IgE and IgG1/G2a ratio in serum, and conjunctival eosinophilic infiltration. Infiltrations of CD11c+ dendritic cells and CD4+ T cells, and the expressions of chemokines and adhesion molecules in the conjunctiva were attenuated in rapamycin-treated mice, as well as decreased Th1 and Th2 cytokines in the cervical lymph nodes compared to non-treated mice. The expression of mTOR signaling proteins was increased in EAC and reduced by rapamycin treatment. Topical application of rapamycin was also proved to show reduced clinical signs, eosinophil infiltration, and Th2 type immune responses comparable to those from intraperitoneal injection of rapamycin. These findings suggest the therapeutic implications of rapamycin in the attenuation of allergic conjunctivitis.
•Rapamycin treatment reduces clinical signs, conjunctival eosinophilic infiltration, IgE in serum and Th2 immune responses.•Expressions of chemokines and adhesion molecules are reduced by rapamycin treatment in experimental allergic conjunctivitis.•Rapamycin attenuates protein expressions in the mTOR pathway providing the alleviating effects of allergic conjunctivitis. |
doi_str_mv | 10.1016/j.clim.2018.02.004 |
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•Rapamycin treatment reduces clinical signs, conjunctival eosinophilic infiltration, IgE in serum and Th2 immune responses.•Expressions of chemokines and adhesion molecules are reduced by rapamycin treatment in experimental allergic conjunctivitis.•Rapamycin attenuates protein expressions in the mTOR pathway providing the alleviating effects of allergic conjunctivitis.</description><identifier>ISSN: 1521-6616</identifier><identifier>EISSN: 1521-7035</identifier><identifier>DOI: 10.1016/j.clim.2018.02.004</identifier><identifier>PMID: 29432811</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Allergic conjunctivitis ; Animals ; Conjunctiva - drug effects ; Conjunctiva - immunology ; Conjunctiva - metabolism ; Conjunctivitis, Allergic - genetics ; Conjunctivitis, Allergic - immunology ; Conjunctivitis, Allergic - prevention & control ; Dendritic cells ; Eosinophil ; Female ; Gene Expression - drug effects ; Gene Expression - immunology ; Immunoglobulin E - blood ; Immunoglobulin E - immunology ; Immunoglobulin G - blood ; Immunoglobulin G - immunology ; Immunosuppressive Agents - pharmacology ; Mice, Inbred BALB C ; Ovalbumin - immunology ; Rapamycin ; Sirolimus - pharmacology ; Th2 Cells - immunology ; Th2 type immune response</subject><ispartof>Clinical immunology (Orlando, Fla.), 2018-05, Vol.190, p.1-10</ispartof><rights>2018 Elsevier Inc.</rights><rights>Copyright © 2018 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-612ae96f597a2dc73d13da3ce00d56dcc519672b7a02a3a2cf51353640bb9f163</citedby><cites>FETCH-LOGICAL-c356t-612ae96f597a2dc73d13da3ce00d56dcc519672b7a02a3a2cf51353640bb9f163</cites><orcidid>0000-0002-1359-5547</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1521661617306551$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29432811$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shin, Soojung</creatorcontrib><creatorcontrib>Lee, Ji Hyun</creatorcontrib><creatorcontrib>Lee, Hyun Jung</creatorcontrib><creatorcontrib>Chang, Sun Young</creatorcontrib><creatorcontrib>Chung, So-Hyang</creatorcontrib><title>Rapamycin attenuates Th2-driven experimental allergic conjunctivitis</title><title>Clinical immunology (Orlando, Fla.)</title><addtitle>Clin Immunol</addtitle><description>Allergic conjunctivitis is mediated by eosinophilic infiltration and Th2 type immune responses. This study aims to elucidate the role of rapamycin, mTOR inhibitor, on OVA-induced experimental allergic conjunctivitis (EAC). Rapamycin administration intraperitoneally markedly reduced clinical signs, total and OVA-specific IgE and IgG1/G2a ratio in serum, and conjunctival eosinophilic infiltration. Infiltrations of CD11c+ dendritic cells and CD4+ T cells, and the expressions of chemokines and adhesion molecules in the conjunctiva were attenuated in rapamycin-treated mice, as well as decreased Th1 and Th2 cytokines in the cervical lymph nodes compared to non-treated mice. The expression of mTOR signaling proteins was increased in EAC and reduced by rapamycin treatment. Topical application of rapamycin was also proved to show reduced clinical signs, eosinophil infiltration, and Th2 type immune responses comparable to those from intraperitoneal injection of rapamycin. These findings suggest the therapeutic implications of rapamycin in the attenuation of allergic conjunctivitis.
•Rapamycin treatment reduces clinical signs, conjunctival eosinophilic infiltration, IgE in serum and Th2 immune responses.•Expressions of chemokines and adhesion molecules are reduced by rapamycin treatment in experimental allergic conjunctivitis.•Rapamycin attenuates protein expressions in the mTOR pathway providing the alleviating effects of allergic conjunctivitis.</description><subject>Allergic conjunctivitis</subject><subject>Animals</subject><subject>Conjunctiva - drug effects</subject><subject>Conjunctiva - immunology</subject><subject>Conjunctiva - metabolism</subject><subject>Conjunctivitis, Allergic - genetics</subject><subject>Conjunctivitis, Allergic - immunology</subject><subject>Conjunctivitis, Allergic - prevention & control</subject><subject>Dendritic cells</subject><subject>Eosinophil</subject><subject>Female</subject><subject>Gene Expression - drug effects</subject><subject>Gene Expression - immunology</subject><subject>Immunoglobulin E - blood</subject><subject>Immunoglobulin E - immunology</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Mice, Inbred BALB C</subject><subject>Ovalbumin - immunology</subject><subject>Rapamycin</subject><subject>Sirolimus - pharmacology</subject><subject>Th2 Cells - immunology</subject><subject>Th2 type immune response</subject><issn>1521-6616</issn><issn>1521-7035</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1rGzEQhkVoSFK3f6CHssdedjszsrRZ6CXkowkECsE5C1mabWX2w5W0Jvn3WWOnx55mDs_7wvsI8QWhQkD9fVO5LvQVAV5WQBXA8kRcoCIsa5Dqw_HXGvW5-JjSBgAUkT4T59QsJV0iXoibJ7u1_asLQ2Fz5mGymVOx-kOlj2HHQ8EvW46h5yHbrrBdx_F3cIUbh800uBx2IYf0SZy2tkv8-XgX4vnudnV9Xz7--vlwffVYOql0LjWS5Ua3qqkteVdLj9Jb6RjAK-2dU9jomta1BbLSkmsVSiX1EtbrpkUtF-LboXcbx78Tp2z6kBx3nR14nJIhAGxQA-GM0gF1cUwpcmu28wobXw2C2dszG7O3Z_b2DJCZ7c2hr8f-ad2z_xd51zUDPw4Azyt3gaNJLvDg2IfILhs_hv_1vwEvPoDC</recordid><startdate>201805</startdate><enddate>201805</enddate><creator>Shin, Soojung</creator><creator>Lee, Ji Hyun</creator><creator>Lee, Hyun Jung</creator><creator>Chang, Sun Young</creator><creator>Chung, So-Hyang</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1359-5547</orcidid></search><sort><creationdate>201805</creationdate><title>Rapamycin attenuates Th2-driven experimental allergic conjunctivitis</title><author>Shin, Soojung ; Lee, Ji Hyun ; Lee, Hyun Jung ; Chang, Sun Young ; Chung, So-Hyang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-612ae96f597a2dc73d13da3ce00d56dcc519672b7a02a3a2cf51353640bb9f163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Allergic conjunctivitis</topic><topic>Animals</topic><topic>Conjunctiva - drug effects</topic><topic>Conjunctiva - immunology</topic><topic>Conjunctiva - metabolism</topic><topic>Conjunctivitis, Allergic - genetics</topic><topic>Conjunctivitis, Allergic - immunology</topic><topic>Conjunctivitis, Allergic - prevention & control</topic><topic>Dendritic cells</topic><topic>Eosinophil</topic><topic>Female</topic><topic>Gene Expression - drug effects</topic><topic>Gene Expression - immunology</topic><topic>Immunoglobulin E - blood</topic><topic>Immunoglobulin E - immunology</topic><topic>Immunoglobulin G - blood</topic><topic>Immunoglobulin G - immunology</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Mice, Inbred BALB C</topic><topic>Ovalbumin - immunology</topic><topic>Rapamycin</topic><topic>Sirolimus - pharmacology</topic><topic>Th2 Cells - immunology</topic><topic>Th2 type immune response</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shin, Soojung</creatorcontrib><creatorcontrib>Lee, Ji Hyun</creatorcontrib><creatorcontrib>Lee, Hyun Jung</creatorcontrib><creatorcontrib>Chang, Sun Young</creatorcontrib><creatorcontrib>Chung, So-Hyang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical immunology (Orlando, Fla.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shin, Soojung</au><au>Lee, Ji Hyun</au><au>Lee, Hyun Jung</au><au>Chang, Sun Young</au><au>Chung, So-Hyang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapamycin attenuates Th2-driven experimental allergic conjunctivitis</atitle><jtitle>Clinical immunology (Orlando, Fla.)</jtitle><addtitle>Clin Immunol</addtitle><date>2018-05</date><risdate>2018</risdate><volume>190</volume><spage>1</spage><epage>10</epage><pages>1-10</pages><issn>1521-6616</issn><eissn>1521-7035</eissn><abstract>Allergic conjunctivitis is mediated by eosinophilic infiltration and Th2 type immune responses. This study aims to elucidate the role of rapamycin, mTOR inhibitor, on OVA-induced experimental allergic conjunctivitis (EAC). Rapamycin administration intraperitoneally markedly reduced clinical signs, total and OVA-specific IgE and IgG1/G2a ratio in serum, and conjunctival eosinophilic infiltration. Infiltrations of CD11c+ dendritic cells and CD4+ T cells, and the expressions of chemokines and adhesion molecules in the conjunctiva were attenuated in rapamycin-treated mice, as well as decreased Th1 and Th2 cytokines in the cervical lymph nodes compared to non-treated mice. The expression of mTOR signaling proteins was increased in EAC and reduced by rapamycin treatment. Topical application of rapamycin was also proved to show reduced clinical signs, eosinophil infiltration, and Th2 type immune responses comparable to those from intraperitoneal injection of rapamycin. These findings suggest the therapeutic implications of rapamycin in the attenuation of allergic conjunctivitis.
•Rapamycin treatment reduces clinical signs, conjunctival eosinophilic infiltration, IgE in serum and Th2 immune responses.•Expressions of chemokines and adhesion molecules are reduced by rapamycin treatment in experimental allergic conjunctivitis.•Rapamycin attenuates protein expressions in the mTOR pathway providing the alleviating effects of allergic conjunctivitis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29432811</pmid><doi>10.1016/j.clim.2018.02.004</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-1359-5547</orcidid></addata></record> |
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subjects | Allergic conjunctivitis Animals Conjunctiva - drug effects Conjunctiva - immunology Conjunctiva - metabolism Conjunctivitis, Allergic - genetics Conjunctivitis, Allergic - immunology Conjunctivitis, Allergic - prevention & control Dendritic cells Eosinophil Female Gene Expression - drug effects Gene Expression - immunology Immunoglobulin E - blood Immunoglobulin E - immunology Immunoglobulin G - blood Immunoglobulin G - immunology Immunosuppressive Agents - pharmacology Mice, Inbred BALB C Ovalbumin - immunology Rapamycin Sirolimus - pharmacology Th2 Cells - immunology Th2 type immune response |
title | Rapamycin attenuates Th2-driven experimental allergic conjunctivitis |
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