title: Suppressor of cytokine signaling-1 (SOCS1) inhibits lymphocyte recruitment into the retina and protects SOCS1 transgenic rats and mice from ocular inflammation.
abstract: OBJECTIVE
  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.affiliation: Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Cheng-Rong
authors.initials: CR
authors.lastname: Yu
authors.forename: Rashid R
authors.initials: RR
authors.lastname: Mahdi
authors.forename: Hyun-Mee
authors.initials: HM
authors.lastname: Oh
authors.forename: Ahjoku
authors.initials: A
authors.lastname: Amadi-Obi
authors.forename: Grace
authors.initials: G
authors.lastname: Levy-Clarke
authors.forename: Jenna
authors.initials: J
authors.lastname: Burton
authors.forename: Amarachi
authors.initials: A
authors.lastname: Eseonu
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Lee
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Charles E
authors.initials: CE
authors.lastname: Egwuagu
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control; D015153:Blotting, Western; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D005136:Eye Proteins; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D012173:Retinitis / Q000276:immunology / Q000517:prevention & control*; D012177:Retinol-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015423:Scleritis / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D014605:Uveitis / Q000276:immunology / Q000517:prevention & control*; D055815:Young Adult; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D016207:Cytokines; D005136:Eye Proteins; D012177:Retinol-Binding Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C491590:Socs1 protein, mouse; C491589:Socs1 protein, rat