Relative contribution of NF-kappaB and AP-1 in the modulation by curcumin and pyrrolidine dithiocarbamate of the UVB-induced cytokine expression by keratinocytes

Abstract

Following ultraviolet B treatment, expression of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 by NCTC 2544 keratinocyte cell line was significantly enhanced both at the mRNA and protein level. The UVB also increased the IL-10 steady-state mRNAs level. Radiation-induced cytokine overexpression was accompanied by NF-kappaB and AP-1 transcription factors activation as assessed by electrophoretic mobility shift assays. To investigate in keratinocytes the relative contributions of those transcription factors on UVB-mediated cytokine induction, cell cultures were supplemented with curcumin and pyrrolidine dithiocarbamate (PDTC), agents known to modulate NF-kappaB and AP-1 activation. Both compounds significantly inhibited NF-kappaB activation by UVB, but AP-1 activation was unaffected by curcumin while PDTC further stimulated its activation. In parallel, curcumin decreased, in a dose-dependent manner, the UVB-mediated overexpression of all three pro-inflammatory cytokines and only exhibited a moderate enhancing influence on IL-10 expression. In turn, the inhibitory influence of PDTC on radiation-induced TNF-alpha and IL-6 expression is much lower and in contrast to curcumin, it stimulated IL-8. Taken together, our data indicated that control of proinflammatory cytokine expression induced by UVB in keratinocytes required the selective inhibition of NF-kappaB activation. Simultaneous AP-1 activation by agents like PDTC might, partially or totally, depending on cytokine-type, counterbalanced the inhibitory effect exerted on UVB-induced NF-kappaB activation in keratinocytes.