Effects of UVA on TNF-α, IL-1β, 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.