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

Photodermatol Photoimmunol Photomed. 2010 Feb;26(1):28-35. doi: 10.1111/j.1600-0781.2009.00481.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology*
  • Antioxidants / pharmacology*
  • Cell Line, Transformed
  • Humans
  • Interleukin-10 / biosynthesis*
  • Interleukin-1beta / biosynthesis*
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Protein Kinase Inhibitors / pharmacology*
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Ultraviolet Rays / adverse effects*
  • Up-Regulation* / drug effects
  • Up-Regulation* / radiation effects
  • Vitamins / pharmacology
  • beta Carotene / pharmacology*

Substances

  • Anthracenes
  • Antioxidants
  • IL10 protein, human
  • Interleukin-1beta
  • Protein Kinase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Vitamins
  • beta Carotene
  • Interleukin-10
  • pyrazolanthrone
  • JNK Mitogen-Activated Protein Kinases