The protective effect of pyruvate against ultraviolet B (UVB)-induced damage was investigated in human immortalized keratinocytes (HaCaT cells). Although pyruvate did not inhibit UVB-induced stimulation of intracellular reactive oxygen species (ROS) levels, it did improve the survival rate of UVB-irradiated HaCaT cells. Furthermore, pyruvate suppressed the UVB-induced mRNA expression of inflammatory mediators such as interleukin (IL)-1 alpha IL-1 beta, IL-6 and cyclooxygenase-2 (Cox-2). This decrease was associated with the reduced secretion of IL-1 alpha, IL-1 beta, IL-6 and prostaglandin E2 (PGE(2)) into culture media. In addition, pyruvate reversed the phosphorylation of p38 mitogen-activated protein kinase (MAPK), induced by UVB-irradiation, in HaCaT cells but increased p38 MAPK phosphorylation in sham-irradiated cells. UVB-induced production of IL-6 was inhibited by SB203580, a p38 MAPK inhibitor. These results suggested that pyruvate inhibits UVB-mediated inflammatory response by inhibiting the p38 MAPK activation. (C) 2012, The Society for Biotechnology, Japan. All rights reserved.