Delayed onset and decreased severity of experimental autoimmune uveoretinitis in mice lacking nitric oxide synthase type 2.
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.
Thillaye-Goldenberg
B
B
INSERM U450, Development, Aging and Pathology of the Retina, 15 rue de l'Ecole de Médecine, 75270 Cedex 06, Paris, France.
Goureau
O
O
Naud
M C
MC
de Kozak
Y
Y
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
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