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Nitric oxide production and inducible nitric oxide synthase expression in systemic sclerosis
T Yamamoto1, I Katayama, K Nishioka
1Department of Dermatology, Tokyo Medical and Dental University School of Medicine, Japan.
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.
Conclusion:
Our results suggest that increased NO levels may contribute to the abnormal regulation of fibroblasts in the fibrotic process in SSc.