Inhibition of Experimental Melanin Protein-induced Uveitis (EMIU) by Targeting Nitric Oxide via Phosphatidylcholine-specific Phospholipase C

• Published in: Journal of autoimmunity Vol. 13; no. 2; pp. 197 - 204
• Main Authors: Matteson, Dawn M, Shen, De Fen, Chan, Chi-Chao
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 01-09-1999; Elsevier
• Subjects: Animals; Apoptosis - drug effects; apoptosis, experimental melanin protein-induced uveitis (EMIU), nitric oxide synthase (NOS), phosphatidylcholine-specific phospholipase C (PC-PLC), tricyclodecan-9-yl-xanthogenate (D609); Autoimmune Diseases - chemically induced; Autoimmune Diseases - drug therapy; Autoimmune Diseases - etiology; Autoimmune Diseases - immunology; Biological and medical sciences; Bridged-Ring Compounds - therapeutic use; Down-Regulation; Enzyme Induction - drug effects; Experimental and animal immunopathology. Animal models; Eye Proteins - immunology; Fas Ligand Protein; Female; Immunopathology; Medical sciences; Melanins - immunology; Membrane Glycoproteins - isolation & purification; Nitric Oxide - metabolism; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase Type II; Ophthalmology; Rats; Rats, Inbred Lew; Thiones - therapeutic use; Type C Phospholipases - antagonists & inhibitors; Uvea - pathology; Uvea diseases; Uveitis - chemically induced; Uveitis - drug therapy; Uveitis - etiology; Uveitis - immunology; apoptosis, experimental melanin protein-induced uveitis (EMIU), nitric oxide synthase (NOS), phosphatidylcholine-specific phospholipase C (PC-PLC), tricyclodecan-9-yl-xanthogenate (D609); Autoimmunity; Animal model; Rat; Pathogenesis; Autoimmune disease; Esterases; Phosphoric diester hydrolases; Uveitis; Immunopathology; Enzyme; Rodentia; Uvea disease; Inflammation; Nitric-oxide synthase; Phospholipase C; Eye disease; Vertebrata; Experimental disease; Mammalia; Uvea; Animal; Nitric oxide; Phosphatidylcholine; Hydrolases; Oxidoreductases; Melanin; Apoptosis
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1006/jaut.1999.0319

Experimental melanin protein-induced uveitis (EMIU) is an autoimmune uveitis induced by immunization with uveal melanin protein. Fas and FasL enhancement is reported in rats with EMIU. Tricyclodecan-9-yl-xanthogenate (D609), a specific inhibitor of phosphatidylcholine-specific phospholipase C, inhibits inducible nitric oxide synthase (iNOS) induction. In two independent experiments, 35 Lewis rats with EMIU received either D609 or PBS daily. The eyes and draining lymph nodes were collected for histology, analyses of nitrite, peroxide, and superoxide dismutase, Fas and FasL immunochemistry, in situ hybridization for iNOS mRNA and in situ apoptosis detection at the peak of the disease. Both experiments showed significant inhibition of EMIU by D609. Decreases in nitrite and peroxide, increase of superoxide dismutase and lower expressions of iNOS mRNA were found in D609-treated, as compared to PBS-treated eyes. There was mild enhancement of Fas and FasL in the eyes and lymph nodes of D609-injected animals. DNA fragmentation was increased in the lymph nodes of D609-treated rats. We conclude that iNOS activation is responsible for NO production in eyes with EMIU. The suppressive effect of D609 on EMIU may result from scavenging NO and activating apoptosis previously inhibited by NO along with other anti-inflammatory effects.