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.
An
Li
L
Department of Environmental Health, School of Public Health, China Medical University, Shenyang, China.
Dong
Guo-Qing
GQ
Gao
Qian
Q
Zhang
Ying
Y
Hu
Li-Wen
LW
Li
Jing-Hai
JH
Liu
Yang
Y
D000873:Anthracenes / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002461:Cell Line, Transformed; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D053583:Interleukin-1beta / Q000096:biosynthesis*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects; D014815:Vitamins / Q000494:pharmacology; D019207:beta Carotene / Q000494:pharmacology*
D000873:Anthracenes; D000975:Antioxidants; C508609:IL10 protein, human; D053583:Interleukin-1beta; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D014815:Vitamins; D019207:beta Carotene; D016753:Interleukin-10; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases