Association between the expression of inducible nitric oxide synthase by chondrocytes and its nitric oxide-generating activity in adjuvant arthritis in rats.
Inducible nitric oxide synthase (iNOS) is one of the clinical targets in rheumatoid arthritis. Synoviocytes, macrophages, and chondrocytes in the joints of patients with rheumatoid arthritis appear to express iNOS, but the contribution of iNOS molecules to rheumatoid arthritis is not yet clear. This study used adjuvant-induced arthritis in rats as a model to examine the association between the iNOS expression and its activity in rheumatoid arthritis. In adjuvant-injected rats, arthritic changes in the paw were first observed between days 10 and 12. NO-generation activity was precisely determined by combining an electron spin resonance/nitric oxide (NO)-trapping method with the method of standard addition using an NO generator, and we found that the activity in the joint samples was extremely high on day 10. The administration of S-(2-aminoethyl)isothiourea, a selective iNOS inhibitor, from day 0 to day 10, effectively reduced the paw swelling. Immunohistological studies showed that chondrocytes expressed iNOS on days 7-14 and that nitrotyrosine residues, a footprint of NO generation, were produced on day 10. This indicates that NO generation by iNOS induced in chondrocytes is a key event in the induction of adjuvant arthritis.
Yonekura
Yukiko
Y
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Koshiishi
Ichiro
I
Yamada
Ken-ichi
K
Mori
Akiko
A
Uchida
Soshi
S
Nakamura
Toshitaka
T
Utsumi
Hideo
H
D000818:Animals; D001169:Arthritis, Experimental / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000201:enzymology* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology
D004791:Enzyme Inhibitors; D000338:beta-Aminoethyl Isothiourea; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat