Pole of p38 mitogen-activated protein kinases in ultraviolet-B irradiation-induced activator protein 1 activation in human keratinocytes

The effects of p38 mitogen-activated protein kinases on ultraviolet. (UV) B irradiation-induced activator protein 1 (AP-1) activation were studied in a human keratinocyte cell line, HaCaT. The HaCaT cells were stably transfec ted with a plasmid containing a promoter fragment of human collagenase 1 dr iving a luciferase reporter gene. There is an AP-1-binding site within this fragment, without any other known transcription factor-binding sites. As w e reported previously, UVB significantly induces activation of AP-1 and p38 in HaCaT cells. SB202190, a p38-specific inhibitor, inhibits UVB-induced p 38 activation and c-fos gene expression. In the present study, we further e xamined the role of p38 in UVB-induced AP-1 activation. We observed that SB 202190 strongly inhibited UVB-induced AP-1 transactivation at different tim e points and UVB doses in transfected HaCaT cells. Furthermore, SB202190 ma rkedly inhibited UVB-induced AP-1 DNA binding as determined by mobility shi ft analyses. These results suggested, for the first time, that activation o f p38 is required for UVB-induced AP-1 activation in human keratinocytes. I n addition, a potential mechanism of UVB-induced AP-1 activation through p3 8 is to enhance AP-1 complex binding to its target DNA. Because c-fos gene expression plays a critical role in UVB-induced AP-1 activation and p38 is required for UVB-induced c-fos gene expression in HaCaT cells, as reported previously, a potential UVB signaling cascade for AP-1 activation in human keratinocytes has been determined. This cascade involves UVB, p38 activatio n, c-fos gene expression, and AP-1 activation. (C) 2000 Wiley-Liss, Inc.