PURPOSE: Suppressors of cytokine signaling (SOCS) proteins regulate the intensity and duration of cytokine signals and defective expression of SOCS1 and SOCS3 has been reported in a number of human diseases. The purpose of this study was to investigate the role of SOCS1 in intraocular inflammatory diseases (uveitis) and whether SOCS1 expression is defective in patients with ocular inflammatory diseases. METHODS: Blood from patients with scleritis or healthy human volunteers was analyzed for SOCS expression by RNase protection assay and RT-PCR. The authors generated SOCS1 transgenic rats and mice (SOCS1-Tg), induced experimental autoimmune uveoretinitis (EAU) by active immunization with interphotoreceptor retinal binding protein or adoptive transfer of uveitogenic T cells, and investigated effects of SOCS1 overexpression on EAU. SOCS1-mediated protection of retinal cells from apoptosis was assessed by annexin V staining. RESULTS: Induction of cytokine-induced SH2 protein was comparable between patients and volunteers, whereas 80% of lymphocytes from patients with scleritis failed to induce SOCS1 in response to IL-2. Compared with wild-type littermates, SOCS1-Tg rats/mice developed less severe EAU. Constitutive overexpression of SOCS1 in retina inhibited expression of chemokines (CCL17, CCL20, CXCL9, CXCL10), reduced Th17/Th1 expansion, and inhibited recruitment of inflammatory cells into the retina. The authors also show that SOCS1 protected retinal cells from staurosporine as well as H₂O₂-induced apoptosis. CONCLUSIONS: Defective expression of SOCS1 in patients with scleritis, taken together with SOCS1-mediated protection of neuroretinal cells from apoptosis, suggest that SOCS1 has neuroprotective function in the retina, implying that administration of SOCS1 mimetic peptides may be useful in treating uveitis or scleritis.
PURPOSE: Suppressors of cytokine signaling (SOCS) proteins regulate the intensity and duration of cytokine signals and defective expression of SOCS1 and SOCS3 has been reported in a number of human diseases. The purpose of this study was to investigate the role of SOCS1 in intraocular inflammatory diseases (uveitis) and whether SOCS1 expression is defective in patients with ocular inflammatory diseases. METHODS: Blood from patients with scleritis or healthy human volunteers was analyzed for SOCS expression by RNase protection assay and RT-PCR. The authors generated SOCS1 transgenic rats and mice (SOCS1-Tg), induced experimental autoimmune uveoretinitis (EAU) by active immunization with interphotoreceptor retinal binding protein or adoptive transfer of uveitogenic T cells, and investigated effects of SOCS1 overexpression on EAU. SOCS1-mediated protection of retinal cells from apoptosis was assessed by annexin V staining. RESULTS: Induction of cytokine-induced SH2 protein was comparable between patients and volunteers, whereas 80% of lymphocytes from patients with scleritis failed to induce SOCS1 in response to IL-2. Compared with wild-type littermates, SOCS1-Tg rats/mice developed less severe EAU. Constitutive overexpression of SOCS1 in retina inhibited expression of chemokines (CCL17, CCL20, CXCL9, CXCL10), reduced Th17/Th1 expansion, and inhibited recruitment of inflammatory cells into the retina. The authors also show that SOCS1 protected retinal cells from staurosporine as well as H₂O₂-induced apoptosis. CONCLUSIONS: Defective expression of SOCS1 in patients with scleritis, taken together with SOCS1-mediated protection of neuroretinal cells from apoptosis, suggest that SOCS1 has neuroprotective function in the retina, implying that administration of SOCS1 mimetic peptides may be useful in treating uveitis or scleritis.
Authors: T Naka; H Tsutsui; M Fujimoto; Y Kawazoe; H Kohzaki; Y Morita; R Nakagawa; M Narazaki; K Adachi; T Yoshimoto; K Nakanishi; T Kishimoto Journal: Immunity Date: 2001-05 Impact factor: 31.745
Authors: Y Morita; T Naka; Y Kawazoe; M Fujimoto; M Narazaki; R Nakagawa; H Fukuyama; S Nagata; T Kishimoto Journal: Proc Natl Acad Sci U S A Date: 2000-05-09 Impact factor: 11.205
Authors: Arpita S Bharadwaj; Binoy Appukuttan; Phillip A Wilmarth; Yuzhen Pan; Andrew J Stempel; Timothy J Chipps; Eric E Benedetti; David O Zamora; Dongseok Choi; Larry L David; Justine R Smith Journal: Prog Retin Eye Res Date: 2012-09-11 Impact factor: 21.198