Nitric oxide production and inducible nitric oxide synthase expression in systemic sclerosis.
OBJECTIVE
We examined whether serum levels of nitric oxide (NO) are elevated in patients with systemic sclerosis (SSc).


METHODS
The concentration of NO was determined by Griess reagents. Immunohistochemical studies were also performed to examine inducible NO synthase (iNOS) protein expression in specimens of lesional skin of SSc. Messenger RNA (mRNA) expression of iNOS was examined by reverse transcriptase-polymerase chain reaction.


RESULTS
The mean serum concentrations of NO were significantly higher in patients with SSc (47.8 +/- 17.0 microM) (mean +/- SD) compared with controls (25.6 +/- 10.3 microM). Immunohistochemical studies showed that iNOS was expressed on infiltrating mononuclear cells, endothelial cells, and fibroblasts in the lesional skin of SSc, while in normal skin iNOS protein was negative on fibroblasts. iNOS gene expression was detected on cultured fibroblasts derived from SSc skin, but not on cultured fibroblasts from normal skin.


CONCLUSIONS
Our results suggest that increased NO levels may contribute to the abnormal regulation of fibroblasts in the fibrotic process in SSc.
Yamamoto
T
T
Department of Dermatology, Tokyo Medical and Dental University School of Medicine, Japan.
Katayama
I
I
Nishioka
K
K
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D012595:Scleroderma, Systemic / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
D012333:RNA, Messenger; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II