title: Delayed onset and decreased severity of experimental autoimmune uveoretinitis in mice lacking nitric oxide synthase type 2.
abstract: To investigate the role of nitric oxide (NO), produced by the inducible form of NO synthase (NOS-2) in the development of experimental autoimmune uveoretinitis (EAU), we immunized C57BL/6x129Sv (H-2(b)) mice carrying a targeted disruption of the gene encoding NOS-2 (NOS-2[-/-]), and wild-type (WT) C57BL/6x129Sv controls with interphotoreceptor retinoid binding protein (IRBP). NOS-2[-/-] mice developed a clinical EAU with delayed onset and decreased severity compared to WT controls. The ocular tissues from WT mice contained activated F4/80 macrophages with NOS-2 expression and retinal destruction whereas less intense EAU was detected in NOS-2[-/-] mice. The expression of NOS-2 mRNA was detected in the retina at the peak of EAU in WT. Analysis of cytokine production in the spleen from NOS-2[-/-] mice by RT-PCR showed high levels of IL-10 mRNA. Our results demonstrate that NO is clearly involved in EAU and may be important for the regulation of immune responses through the regulation of IL-10.
authors.affiliation: INSERM U450, Development, Aging and Pathology of the Retina, 15 rue de l'Ecole de Médecine, 75270 Cedex 06, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Thillaye-Goldenberg
authors.forename: O
authors.initials: O
authors.lastname: Goureau
authors.forename: M C
authors.initials: MC
authors.lastname: Naud
authors.forename: Y
authors.initials: Y
authors.lastname: de Kozak
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D003208:Concanavalin A / Q000494:pharmacology; D005136:Eye Proteins; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D012160:Retina / Q000201:enzymology / Q000276:immunology; D012173:Retinitis / Q000276:immunology* / Q000378:metabolism*; D012177:Retinol-Binding Proteins / Q000276:immunology / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D014605:Uveitis / Q000276:immunology* / Q000378:metabolism*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D003208:Concanavalin A; D005136:Eye Proteins; D007074:Immunoglobulin G; D007371:Interferon-gamma; D016753:Interleukin-10; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger; D012177:Retinol-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D000099214:Retinol-Binding Proteins, Interstitial; C496317:Nos2 protein, mouse