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
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.