A cell permeable peptide inhibitor of NFAT inhibits macrophage cytokine expression and ameliorates experimental colitis
Nuclear factor of activated T cells (NFAT) plays a critical role in the development and function of immune and non-immune cells. Although NFAT is a central transcriptional regulator of T cell cytokines, its role in macrophage specific gene expression is less defined. Previous work from our group dem...
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| Veröffentlicht in: | PloS one 2012-03, Vol.7 (3), p.e34172-e34172 |
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| creator | Elloumi, Houda Z Maharshak, Nitsan Rao, Kavitha N Kobayashi, Taku Ryu, Hyungjin S Mühlbauer, Marcus Li, Fengling Jobin, Christian Plevy, Scott E |
| description | Nuclear factor of activated T cells (NFAT) plays a critical role in the development and function of immune and non-immune cells. Although NFAT is a central transcriptional regulator of T cell cytokines, its role in macrophage specific gene expression is less defined. Previous work from our group demonstrated that NFAT regulates Il12b gene expression in macrophages. Here, we further investigate NFAT function in murine macrophages and determined the effects of a cell permeable NFAT inhibitor peptide 11R-VIVIT on experimental colitis in mice. Treatment of bone marrow derived macrophages (BMDMs) with tacrolimus or 11R-VIVIT significantly inhibited LPS and LPS plus IFN-γ induced IL-12 p40 mRNA and protein expression. IL-12 p70 and IL-23 secretion were also decreased. NFAT nuclear translocation and binding to the IL-12 p40 promoter was reduced by NFAT inhibition. Experiments in BMDMs from IL-10 deficient (Il10(-/-)) mice demonstrate that inhibition of IL-12 expression by 11R-VIVIT was independent of IL-10 expression. To test its therapeutic potential, 11R-VIVIT was administered systemically to Il10(-/-) mice with piroxicam-induced colitis. 11R-VIVIT treated mice demonstrated significant improvement in colitis compared to mice treated with an inactive peptide. Moreover, decreased spontaneous secretion of IL-12 p40 and TNF in supernatants from colon explant cultures was demonstrated. In summary, NFAT, widely recognized for its role in T cell biology, also regulates important innate inflammatory pathways in macrophages. Selective blocking of NFAT via a cell permeable inhibitory peptide is a promising therapeutic strategy for the treatment of inflammatory bowel diseases. |
| doi_str_mv | 10.1371/journal.pone.0034172 |
| format | Article |
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Although NFAT is a central transcriptional regulator of T cell cytokines, its role in macrophage specific gene expression is less defined. Previous work from our group demonstrated that NFAT regulates Il12b gene expression in macrophages. Here, we further investigate NFAT function in murine macrophages and determined the effects of a cell permeable NFAT inhibitor peptide 11R-VIVIT on experimental colitis in mice. Treatment of bone marrow derived macrophages (BMDMs) with tacrolimus or 11R-VIVIT significantly inhibited LPS and LPS plus IFN-γ induced IL-12 p40 mRNA and protein expression. IL-12 p70 and IL-23 secretion were also decreased. NFAT nuclear translocation and binding to the IL-12 p40 promoter was reduced by NFAT inhibition. Experiments in BMDMs from IL-10 deficient (Il10(-/-)) mice demonstrate that inhibition of IL-12 expression by 11R-VIVIT was independent of IL-10 expression. To test its therapeutic potential, 11R-VIVIT was administered systemically to Il10(-/-) mice with piroxicam-induced colitis. 11R-VIVIT treated mice demonstrated significant improvement in colitis compared to mice treated with an inactive peptide. Moreover, decreased spontaneous secretion of IL-12 p40 and TNF in supernatants from colon explant cultures was demonstrated. In summary, NFAT, widely recognized for its role in T cell biology, also regulates important innate inflammatory pathways in macrophages. Selective blocking of NFAT via a cell permeable inhibitory peptide is a promising therapeutic strategy for the treatment of inflammatory bowel diseases.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0034172</identifier><identifier>PMID: 22479554</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Active Transport, Cell Nucleus ; Animals ; Antigens ; Autoimmune diseases ; B cells ; Biology ; Bone marrow ; Bone Marrow Cells - cytology ; Colitis ; Colitis - metabolism ; Colitis - therapy ; Colon ; Cooperation ; Cytokines ; Cytokines - biosynthesis ; Dendritic cells ; Deoxyribonucleic acid ; Departments ; Disease Models, Animal ; DNA ; Drug therapy ; Gene expression ; Genes ; Green Fluorescent Proteins - metabolism ; IL12B protein ; Immune system ; Immunology ; Inflammation ; Inflammatory bowel disease ; Inflammatory bowel diseases ; Inhibition ; Inhibitors ; Interferon ; Interferon-gamma - metabolism ; Interleukin 1 ; Interleukin 10 ; Interleukin 12 ; Interleukin 23 ; Interleukin-10 - genetics ; Interleukin-12 Subunit p40 - metabolism ; Intestine ; Kinases ; Lipopolysaccharides ; Lipopolysaccharides - metabolism ; Lymphocytes ; Lymphocytes T ; Macrophages ; Macrophages - cytology ; Macrophages - metabolism ; Medical treatment ; Medicine ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Fluorescence - methods ; NF-AT protein ; NFATC Transcription Factors - antagonists & inhibitors ; NFATC Transcription Factors - metabolism ; Nitric Oxide Synthase Type II - genetics ; Nuclear transport ; Pathogenesis ; Peptides ; Permeability ; Phosphatase ; Piroxicam ; Promoter Regions, Genetic ; Proteins ; RNA ; RNA, Messenger - metabolism ; T cells ; Tacrolimus ; Tacrolimus - pharmacology ; Transcription (Genetics) ; Transcription factors ; Translocation ; Tumor necrosis factor ; γ-Interferon</subject><ispartof>PloS one, 2012-03, Vol.7 (3), p.e34172-e34172</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Elloumi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Elloumi et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-853daf011435af61cc8d46cd435bad4a70b55b20ad0e214a626d4c39f01030f83</citedby><cites>FETCH-LOGICAL-c757t-853daf011435af61cc8d46cd435bad4a70b55b20ad0e214a626d4c39f01030f83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313977/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313977/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22479554$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Combs, Colin</contributor><creatorcontrib>Elloumi, Houda Z</creatorcontrib><creatorcontrib>Maharshak, Nitsan</creatorcontrib><creatorcontrib>Rao, Kavitha N</creatorcontrib><creatorcontrib>Kobayashi, Taku</creatorcontrib><creatorcontrib>Ryu, Hyungjin S</creatorcontrib><creatorcontrib>Mühlbauer, Marcus</creatorcontrib><creatorcontrib>Li, Fengling</creatorcontrib><creatorcontrib>Jobin, Christian</creatorcontrib><creatorcontrib>Plevy, Scott E</creatorcontrib><title>A cell permeable peptide inhibitor of NFAT inhibits macrophage cytokine expression and ameliorates experimental colitis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Nuclear factor of activated T cells (NFAT) plays a critical role in the development and function of immune and non-immune cells. Although NFAT is a central transcriptional regulator of T cell cytokines, its role in macrophage specific gene expression is less defined. Previous work from our group demonstrated that NFAT regulates Il12b gene expression in macrophages. Here, we further investigate NFAT function in murine macrophages and determined the effects of a cell permeable NFAT inhibitor peptide 11R-VIVIT on experimental colitis in mice. Treatment of bone marrow derived macrophages (BMDMs) with tacrolimus or 11R-VIVIT significantly inhibited LPS and LPS plus IFN-γ induced IL-12 p40 mRNA and protein expression. IL-12 p70 and IL-23 secretion were also decreased. NFAT nuclear translocation and binding to the IL-12 p40 promoter was reduced by NFAT inhibition. Experiments in BMDMs from IL-10 deficient (Il10(-/-)) mice demonstrate that inhibition of IL-12 expression by 11R-VIVIT was independent of IL-10 expression. To test its therapeutic potential, 11R-VIVIT was administered systemically to Il10(-/-) mice with piroxicam-induced colitis. 11R-VIVIT treated mice demonstrated significant improvement in colitis compared to mice treated with an inactive peptide. Moreover, decreased spontaneous secretion of IL-12 p40 and TNF in supernatants from colon explant cultures was demonstrated. In summary, NFAT, widely recognized for its role in T cell biology, also regulates important innate inflammatory pathways in macrophages. Selective blocking of NFAT via a cell permeable inhibitory peptide is a promising therapeutic strategy for the treatment of inflammatory bowel diseases.</description><subject>Active Transport, Cell Nucleus</subject><subject>Animals</subject><subject>Antigens</subject><subject>Autoimmune diseases</subject><subject>B cells</subject><subject>Biology</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - cytology</subject><subject>Colitis</subject><subject>Colitis - metabolism</subject><subject>Colitis - therapy</subject><subject>Colon</subject><subject>Cooperation</subject><subject>Cytokines</subject><subject>Cytokines - biosynthesis</subject><subject>Dendritic cells</subject><subject>Deoxyribonucleic acid</subject><subject>Departments</subject><subject>Disease Models, Animal</subject><subject>DNA</subject><subject>Drug therapy</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>IL12B protein</subject><subject>Immune system</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Inflammatory bowel disease</subject><subject>Inflammatory bowel diseases</subject><subject>Inhibition</subject><subject>Inhibitors</subject><subject>Interferon</subject><subject>Interferon-gamma - metabolism</subject><subject>Interleukin 1</subject><subject>Interleukin 10</subject><subject>Interleukin 12</subject><subject>Interleukin 23</subject><subject>Interleukin-10 - genetics</subject><subject>Interleukin-12 Subunit p40 - metabolism</subject><subject>Intestine</subject><subject>Kinases</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - metabolism</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Macrophages - cytology</subject><subject>Macrophages - metabolism</subject><subject>Medical treatment</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Fluorescence - methods</subject><subject>NF-AT protein</subject><subject>NFATC Transcription Factors - antagonists & inhibitors</subject><subject>NFATC Transcription Factors - metabolism</subject><subject>Nitric Oxide Synthase Type II - genetics</subject><subject>Nuclear transport</subject><subject>Pathogenesis</subject><subject>Peptides</subject><subject>Permeability</subject><subject>Phosphatase</subject><subject>Piroxicam</subject><subject>Promoter Regions, Genetic</subject><subject>Proteins</subject><subject>RNA</subject><subject>RNA, Messenger - metabolism</subject><subject>T cells</subject><subject>Tacrolimus</subject><subject>Tacrolimus - pharmacology</subject><subject>Transcription (Genetics)</subject><subject>Transcription factors</subject><subject>Translocation</subject><subject>Tumor necrosis factor</subject><subject>γ-Interferon</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYqPwDxBEQgJx0eKvxMkNUjUxqDQxCQa31qnttB5OHGwHtn-PS9OpQbtAvrB9_JzX9vnIsucYLTDl-N21G3wHdtG7Ti8Qogxz8iA7xTUl85Ig-vBofZI9CeEaoYJWZfk4OyGE8boo2Gn2e5lLbW3ea99qWFudVn00Suem25q1ic7nrsk_ny-vDpaQtyC967ew0bm8je6H6XSub3qvQzCuy6FTObTaGuch6rA70t60uotgc-msiSY8zR41YIN-Ns6z7Nv5h6uzT_OLy4-rs-XFXPKCx3lVUAUNwpjRApoSS1kpVkqVtmtQDDhaF8WaIFBIE8ygJKViktbJBVHUVHSWvdzr9tYFMcYsCEwZonXBEjXLVntCObgWfXoo-FvhwIi_Buc3Anw00mqhCixRRQhSHDHMmkrWiDe0VFWFOIGd1vvxtmHdaiXTlz3Yiej0pDNbsXG_BKWY1pwngTejgHc_Bx2iaE3YJQg67YYg6ppUpEr5T-Srf8j7PzdSG0jvN13j0rVypymWjHOEy6SYqMU9VBpKt0am-mpMsk8c3k4cEhP1TdzAEIJYff3y_-zl9yn7-ojdarBxG5wdYiqrMAXZHkyFGILXzV2MMRK79jhEQ-zaQ4ztkdxeHOfnzunQD_QPCEQK_w</recordid><startdate>20120327</startdate><enddate>20120327</enddate><creator>Elloumi, Houda Z</creator><creator>Maharshak, Nitsan</creator><creator>Rao, Kavitha N</creator><creator>Kobayashi, Taku</creator><creator>Ryu, Hyungjin S</creator><creator>Mühlbauer, Marcus</creator><creator>Li, Fengling</creator><creator>Jobin, Christian</creator><creator>Plevy, Scott E</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120327</creationdate><title>A cell permeable peptide inhibitor of NFAT inhibits macrophage cytokine expression and ameliorates experimental colitis</title><author>Elloumi, Houda Z ; Maharshak, Nitsan ; Rao, Kavitha N ; Kobayashi, Taku ; Ryu, Hyungjin S ; Mühlbauer, Marcus ; Li, Fengling ; Jobin, Christian ; Plevy, Scott E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-853daf011435af61cc8d46cd435bad4a70b55b20ad0e214a626d4c39f01030f83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Active Transport, Cell Nucleus</topic><topic>Animals</topic><topic>Antigens</topic><topic>Autoimmune diseases</topic><topic>B cells</topic><topic>Biology</topic><topic>Bone marrow</topic><topic>Bone Marrow Cells - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Elloumi, Houda Z</au><au>Maharshak, Nitsan</au><au>Rao, Kavitha N</au><au>Kobayashi, Taku</au><au>Ryu, Hyungjin S</au><au>Mühlbauer, Marcus</au><au>Li, Fengling</au><au>Jobin, Christian</au><au>Plevy, Scott E</au><au>Combs, Colin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A cell permeable peptide inhibitor of NFAT inhibits macrophage cytokine expression and ameliorates experimental colitis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-03-27</date><risdate>2012</risdate><volume>7</volume><issue>3</issue><spage>e34172</spage><epage>e34172</epage><pages>e34172-e34172</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Nuclear factor of activated T cells (NFAT) plays a critical role in the development and function of immune and non-immune cells. Although NFAT is a central transcriptional regulator of T cell cytokines, its role in macrophage specific gene expression is less defined. Previous work from our group demonstrated that NFAT regulates Il12b gene expression in macrophages. Here, we further investigate NFAT function in murine macrophages and determined the effects of a cell permeable NFAT inhibitor peptide 11R-VIVIT on experimental colitis in mice. Treatment of bone marrow derived macrophages (BMDMs) with tacrolimus or 11R-VIVIT significantly inhibited LPS and LPS plus IFN-γ induced IL-12 p40 mRNA and protein expression. IL-12 p70 and IL-23 secretion were also decreased. NFAT nuclear translocation and binding to the IL-12 p40 promoter was reduced by NFAT inhibition. Experiments in BMDMs from IL-10 deficient (Il10(-/-)) mice demonstrate that inhibition of IL-12 expression by 11R-VIVIT was independent of IL-10 expression. To test its therapeutic potential, 11R-VIVIT was administered systemically to Il10(-/-) mice with piroxicam-induced colitis. 11R-VIVIT treated mice demonstrated significant improvement in colitis compared to mice treated with an inactive peptide. Moreover, decreased spontaneous secretion of IL-12 p40 and TNF in supernatants from colon explant cultures was demonstrated. In summary, NFAT, widely recognized for its role in T cell biology, also regulates important innate inflammatory pathways in macrophages. Selective blocking of NFAT via a cell permeable inhibitory peptide is a promising therapeutic strategy for the treatment of inflammatory bowel diseases.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22479554</pmid><doi>10.1371/journal.pone.0034172</doi><tpages>e34172</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-03, Vol.7 (3), p.e34172-e34172 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1340395410 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Active Transport, Cell Nucleus Animals Antigens Autoimmune diseases B cells Biology Bone marrow Bone Marrow Cells - cytology Colitis Colitis - metabolism Colitis - therapy Colon Cooperation Cytokines Cytokines - biosynthesis Dendritic cells Deoxyribonucleic acid Departments Disease Models, Animal DNA Drug therapy Gene expression Genes Green Fluorescent Proteins - metabolism IL12B protein Immune system Immunology Inflammation Inflammatory bowel disease Inflammatory bowel diseases Inhibition Inhibitors Interferon Interferon-gamma - metabolism Interleukin 1 Interleukin 10 Interleukin 12 Interleukin 23 Interleukin-10 - genetics Interleukin-12 Subunit p40 - metabolism Intestine Kinases Lipopolysaccharides Lipopolysaccharides - metabolism Lymphocytes Lymphocytes T Macrophages Macrophages - cytology Macrophages - metabolism Medical treatment Medicine Mice Mice, Inbred C57BL Mice, Transgenic Microscopy, Fluorescence - methods NF-AT protein NFATC Transcription Factors - antagonists & inhibitors NFATC Transcription Factors - metabolism Nitric Oxide Synthase Type II - genetics Nuclear transport Pathogenesis Peptides Permeability Phosphatase Piroxicam Promoter Regions, Genetic Proteins RNA RNA, Messenger - metabolism T cells Tacrolimus Tacrolimus - pharmacology Transcription (Genetics) Transcription factors Translocation Tumor necrosis factor γ-Interferon |
| title | A cell permeable peptide inhibitor of NFAT inhibits macrophage cytokine expression and ameliorates experimental colitis |
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