p38 alpha MAP Kinase Controls IL-17 Synthesis in Vogt-Koyanagi-Harada Syndrome and Experimental Autoimmune Uveitis

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dc.contributor.author Commodaro, Alessandra Goncalves [UNIFESP]
dc.contributor.author Bombardieri, Cintia Raquel
dc.contributor.author Schatzmann Peron, Jean Pierre
dc.contributor.author Saito, Kelly Cristina
dc.contributor.author Guedes, Pedro Mancini
dc.contributor.author Hamassaki, Dania E.
dc.contributor.author Belfort, Rubens Neto [UNIFESP]
dc.contributor.author Rizzo, Luiz Vicente
dc.contributor.author Belfort, Rubens Junior [UNIFESP]
dc.contributor.author Camargo, Maristela Martins de
dc.date.accessioned 2016-01-24T14:05:04Z
dc.date.available 2016-01-24T14:05:04Z
dc.date.issued 2010-07-01
dc.identifier http://dx.doi.org/10.1167/iovs.09-4393
dc.identifier.citation Investigative Ophthalmology & Visual Science. Rockville: Assoc Research Vision Ophthalmology Inc, v. 51, n. 7, p. 3567-3574, 2010.
dc.identifier.issn 0146-0404
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/32653
dc.description.abstract PURPOSE. Interleukin (IL)-17, which is responsible for the initial influx of leukocytes into the target tissue, was recently described as the main cytokine involved in autoimmune diseases. Vogt-Koyanagi-Harada (VKH) syndrome is a significant cause of noninfectious blindness in the world. Herein the authors aimed at unraveling the involvement of IL-17 in VKH and in experimental autoimmune uveitis, focusing on the signaling pathways involved in IL-17 synthesis.METHODS. Mice were immunized with 161-180 peptide and pertussis toxin. Draining lymph node cells, harvested 21 days after immunization, were cultured in the presence or absence of p38 alpha mitogen-activated protein kinase (MAPK) inhibitor (SB203580) and assayed for cytokine production and quantification of CD4(+)IL-17(+) cells. Mice received intraocular injections of SB203580, and disease severity was evaluated by histologic examination of the enucleated eyes at day 21. CD4(+) lymphocytes from MSK-1/2-deficient mice, human CD4(+) cells silenced with MSK1 siRNA, or peripheral blood mononuclear cells (PBMCs) from VKH patients were cultured in the presence or absence of p38 alpha MAPK inhibitor and then assayed for IL-17, IFN-gamma, and IL-4 production.RESULTS. the inhibition of p38 alpha MAPK fully blocked the synthesis of IL-17 by PBMCs from VKH patients and lymphocytes from EAU mice. the absence of the msk1/2 gene resulted in failure to produce IL-17 by murine and human lymphocytes. Interestingly, intraocular injections of SB203580 in EAU mice did not suppress development of the disease.CONCLUSIONS. These data show that p38 alpha MAPK-MSK1/2 is involved in the control of IL-17 synthesis by CD4(+) T cells and that inhibition of p38 alpha MAPK in vitro suppresses IL-17 synthesis but that inhibition of this kinase in vivo did not protect from EAU. (Invest Ophthalmol Vis Sci. 2010;51:3567-3574) DOI: 10.1167/iovs.09-4393 en
dc.description.sponsorship São Paulo State Science Council
dc.description.sponsorship Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.format.extent 3567-3574
dc.language.iso eng
dc.publisher Assoc Research Vision Ophthalmology Inc
dc.relation.ispartof Investigative Ophthalmology & Visual Science
dc.rights Acesso aberto
dc.title p38 alpha MAP Kinase Controls IL-17 Synthesis in Vogt-Koyanagi-Harada Syndrome and Experimental Autoimmune Uveitis en
dc.type Artigo
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Albert Einstein Jewish Inst Educ & Res
dc.description.affiliation Univ São Paulo, Inst Biomed Sci, Dept Immunol, BR-05508900 São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Vis Inst, São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-05508900 São Paulo, Brazil
dc.description.affiliation Albert Einstein Jewish Inst Educ & Res, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Vis Inst, São Paulo, Brazil
dc.description.sponsorshipID São Paulo State Science Council: 01/02584-2
dc.description.sponsorshipID CAPES: PNPD 0188085
dc.identifier.doi 10.1167/iovs.09-4393
dc.description.source Web of Science
dc.identifier.wos WOS:000279047500034



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