Delayed onset and decreased severity of experimental autoimmune uveoretinitis in mice lacking nitric oxide synthase type 2

• Published in: Journal of neuroimmunology 2000-10, Vol.110 (1), p.31-44
• Main Authors: Thillaye-Goldenberg, B, Goureau, O, Naud, M.C, de Kozak, Y
• Format: Article
• Language: English
• Subjects: Animals; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; Cell Division; Concanavalin A - pharmacology; Experimental autoimmune uveoretinitis; Eye Proteins; Female; Gene Expression Regulation, Enzymologic - immunology; IL-10; Immunization; Immunoglobulin G - blood; Inflammation; Interferon-gamma - genetics; Interferon-gamma - immunology; Interleukin-10 - genetics; Interleukin-10 - immunology; Knock-out mice; Lymphocytes - cytology; Lymphocytes - immunology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide - metabolism; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type II; Regulation; Retina - enzymology; Retina - immunology; Retinitis - immunology; Retinitis - metabolism; retinoid-binding protein; Retinol-Binding Proteins - immunology; Retinol-Binding Proteins - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Severity of Illness Index; Spleen - immunology; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Uveitis - immunology; Uveitis - metabolism
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(00)00313-1

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/6×129Sv (H-2 b) mice carrying a targeted disruption of the gene encoding NOS-2 (NOS-2[−/−]), and wild-type (WT) C57BL/6×129Sv 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.