Ultraviolet irradiation induces cyclooxygenase-2 expression in keratinocytes

Abstract

We examined the effect of ultraviolet (UV) irradiation on the expression of cyclooxygenases in cultured HaCaT keratinocytes and in human skin in vivo. UVB irradiation (10 and 50 mJ/cm2) and hydrogen peroxide (200 micromol/L) increased cyclooxygenase-2 mRNA expression in HaCaT keratinocytes. No clear expression of cyclooxygenase-1 mRNA was detected in either control or stimulated HaCaT cells. Genistein, a tyrosine kinase inhibitor, suppressed both the basal and stimulated expression of cyclooxygenase-2 in HaCaT cells. UVB-induced cyclooxygenase-2 mRNA expression was partly inhibited by the antioxidant N-acetylcysteine and by H-7, a non-specific inhibitor of protein kinase C. Solar-simulated irradiation (40 mJ/cm2) was found to induce in vivo both cyclooxygenase-2 mRNA and protein expression in human skin, whereas the expression of cyclooxygenase-1 mRNA remained at the basal level. Our results show that cyclooxygenase-2 expression is induced by UV irradiation and suggest that tyrosine kinases and reactive oxygen intermediates are involved in this induction of cyclooxygenase-2.

UVB light upregulates prostaglandin synthases and prostaglandin receptors in mouse keratinocytes

“…We found that COX-2 mRNA and protein were increased in mouse keratinocytes following UVB exposure. These data are consistent with earlier reports showing that UVB effectively induces COX-2 in mouse and human keratinocytes (Isoherranen et al, 1999;Black et al, 2008). Our data also demonstrate that differentiated cells are more sensitive to UVB-induced upregulation of COX-2 mRNA and protein, a finding consistent with previous studies showing that UVB-induced COX-2 expression in mouse skin occurs primarily in the suprabasal, differentiated keratinocytes (Athar et al, 2001).…”

“…Metabolism of PGH 2 leads to the generation of PGD 2 , PGE 2 , PGF 2 , PGI 2 and thromboxane A 2 which are synthesized by PGD 2 synthase, PGE 2 synthase, PGF 2 synthase, PGI 2 synthase and thromboxane A 2 synthase, respectively (Helliwell et al, 2004). Exposure to UVB light, which is known to cause cutaneous inflammation and cancer (Hruza and Pentland, 1993), has been reported to upregulate COX-2 in human and mouse skin (Buckman et al, 1998;Isoherranen et al, 1999;Chen et al, 2001;Bachelor et al, 2005), a process linked to many of its biological effects (Fitzpatrick, 2004). Increased concentrations of PGE 2 , PGF 2α and PGD 2 have been detected in UVB-exposed skin (Black et al, 1980a) and, in cultured keratinocytes, PGE 2 is the predominant prostaglandin identified following UVB exposure (Miller et al, 1994).…”

The role of p38 in UVA-induced cyclooxygenase-2 expression in the human keratinocyte cell line, HaCaT

“…Soriani et al (1998) previously showed that UVA-induced COX-2 mRNA expression was decreased by epigallocatechin in the human oral carcinoma cell line KB but not in the human skin fibroblast cell line FEK4. Induction of COX-2 mRNA was also reported in response to solar simulated irradiation of human skin (Isoherranen et al, 1999). At this time, however no study has addressed the role of the UVA spectrum alone in the expression of COX-2 in a model of nonmelanoma skin cancer.…”

Role of cyclic AMP responsive element in the UVB induction of cyclooxygenase-2 transcription in human keratinocytes

“…UVB induced COX-2 expression in human skin (Buckman et al, 1998;Isoherranen et al, 1999), and oral administration of selective COX-2 inhibitor, celecoxib, produced a decrease in the tumor number and multiplicity in UV-treated hairless mice (Pentland et al, 1999). In view of the importance of COX-2 in UVB-induced tumorigenesis, we have begun to characterize the signaling pathway of UVB induction of COX-2 in human keratinocytes, HaCaT (Chen et al, 2001).…”