Cyclooxygenase-2 expression and prostaglandin E-2 biosynthesis are enhanced in scleroderma fibroblasts and inhibited by UVA irradiation

Citation
T. Kanekura et al., Cyclooxygenase-2 expression and prostaglandin E-2 biosynthesis are enhanced in scleroderma fibroblasts and inhibited by UVA irradiation, J RHEUMATOL, 28(7), 2001, pp. 1568-1572
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Rheumatology,"da verificare
Journal title
JOURNAL OF RHEUMATOLOGY
ISSN journal
0315-162X → ACNP
Volume
28
Issue
7
Year of publication
2001
Pages
1568 - 1572
Database
ISI
SICI code
0315-162X(200107)28:7<1568:CEAPEB>2.0.ZU;2-L
Abstract
Objective. We and others reported on the beneficial effects of combined the rapy using 8-methoxypsoralen and long wave ultraviolet Light (PUVA therapy) in the treatment of scleroderma. We now investigate the mechanism by which PUVA therapy is effective by comparing interleukin 1 beta (IL-1 beta) medi ated signal transduction in scleroderma fibroblasts and those from normal s kin. Methods. Prostaglandin E-2 (PGE,) production and expression of cytosolic ph ospholipase A, (cPLA(2)), cyclooxygenase (COX)-1, and COX-2 (enzymes that r egulate PGE(2) production) were examined in untreated and IL-1 alpha treate d fibroblasts from scleroderma involved and normal skin. The effect of UVA irradiation on enzyme expression and PGE(2) production was examined. PGE(2) was measured by a competitive radioimmunoassay and enzyme expression was a nalyzed by Western immunoblotting and Northern blotting. Results. Constitutive PGE(2) production was significantly upregulated and I L-1 beta induced PGE, production was increased by the enhancing expression of both COX-2 mRNA and protein in fibroblasts from scleroderma involved ski n; PGE(2) production and COX-2 expression were inhibited by UVA irradiation . Conclusion, Enhanced PGE(2) production regulated by COX-2 expression in scl eroderma fibroblasts may contribute to the development of this disorder. PU VA therapy might exhibit its beneficial effect, at least in part, by inhibi ting COX-2 expression transcriptionally and translationally, with subsequen t inhibition of PGE(2) production.