Effects of UVA on TNF-alpha, IL-1beta, and IL-10 expression levels in human keratinocytes and intervention studies with an antioxidant and a JNK inhibitor.

OBJECTIVE

To understand the expressions and transduction pathways of cytokines in ultraviolet (UV)A-irradiated keratinocytes.

METHODS

We cultured human keratinocytes of the HaCaT cell line and investigated both mRNA and protein expressions of cytokines in cells that were not irradiated or were exposed to 2.4 J/cm(2) UVA, with or without an antioxidant (beta-carotene) or a c-Jun N-terminal kinase (JNK) inhibitor (SP600125).

RESULTS

We demonstrated that the expression levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta were up-regulated in irradiated cells. IL-10 was not detected in non-irradiated cells, but was observed in irradiated cells. JNK was activated in irradiated cells and this could be antagonized by beta-carotene. The UVA-induced up-regulation of these cytokines was also antagonized by beta-carotene. SP600125 inhibited the UVA-induced increase in the expression of TNF-alpha mRNA and protein and in the expression of IL-1beta mRNA.

CONCLUSIONS

The results suggest that oxidative stress may be an early intermediate effect in JNK-dependent UVA induction of cytokine expression in human keratinocytes in vitro.