UVB radiation-mediated expression of inducible nitric oxide synthase activity and the augmenting role of co-induced TNF-α in human skin endothelial cells

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:123

Article

Suschek, CV ; Mahotka, C ; Schnorr, O ; Kolb-Bachofen, V

关键词: cationic amino acid transporter;    cytokines;    endothelial cells;    inducible nitric oxide synthase;    nitric oxide;    TNF-alpha;    UVB;   

DOI  :  10.1111/j.0022-202X.2004.23422.x

来源: Elsevier

【 摘 要 】

Nitric oxide (NO) plays a pivotal role in ultraviolet radiation-induced inflammation in human skin. We had earlier reported on the inducible nitric oxide synthase (iNOS) inducing activity of UVA radiation. We now demonstrate that UVB-exposure induces expression of the iNOS in vessel endothelia of normal human skin and in cultured human dermal endothelial cells (HUDEC), although by a molecular mechanism different from UVA-mediated induction. With HUDEC, UVB induces iNOS expression and leads to significant enzyme activities, although at app. 5-fold lower levels than can be achieved with proinflammatory cytokines. In contrast to our earlier observation with UVA, cytokine-challenge combined with simultaneous UVB-exposure had no additive effects on iNOS expression nor activity. Interestingly, a time-delay between UVB-irradiation and cytokine-challenge enhances endothelial iNOS enzyme activity 2.5-fold over cytokines activation only. This time-dependent effect strongly correlates with UVB-induced endothelial TNF-alpha expression. In HUDEC addition of TNF-alpha results in enhanced expression of the inducible arginine transporter system CAT-2 essential for substrate supply and thus iNOS activity. In summary, UVB induces iNOS mRNA and enzyme activity in HUDEC. Moreover, UVB augments CAT-2 expression through a TNF-alpha- dependent mechanism which essentially contributes to increased iNOS activity.

【 授权许可】

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