Previously, wogonin (5,7-dihydroxy-8-methoxyflavone) was found to suppress proinflammatory enzyme expression including cyclooxygenase-2 (COX-2), contributing to in vivo anti-inflammatory activity against skin inflammation. However, the detailed effect on each skin cell type has not been understood. Therefore, present investigation was carried out to find the effect of wogonin on inflammation associated gene expression from skin fibroblasts in culture using reverse transcriptase-polymerase chain reaction. As a result, it was found that wogonin (10-100 muM) clearly down-regulated COX-2 expression from NIH/3T3 cells treated with 12-O-tetradecanoylphorbol 13-acetate, interleukin-1beta or tumor necrosis factor-alpha. But, the expression levels of COX-1, interleukin-1beta and fibronectin were not significantly affected. This finding was well correlated with significant reduction of prostaglandin E-2 (PGE(2)) production by wogonin. As a comparison, NS-398 (selective cyclooxygenase 2 inhibitor) did not suppress COX-2 expression and other gene levels, while PGE2 production was potently reduced at 0.1-10 muM. All these results suggest that COX-2 down-regulation of skin fibroblasts may be, at least in part, one of anti-inflammatory mechanisms of wogonin against skin inflammation. (C) 2004 Elsevier Ltd. All rights reserved.