curcumin and nickel-sulfate

Nickel can induce cellular and nuclear damages responsible for chronic diseases, like allergic contact dermatitis (ACD). We previously showed that matrix metalloproteinase-2 (MMP-2) gene expression was induced by nickel in nontumorigenic human keratinocytes cell line (HaCat).. To investigate the signal transduction pathways involved in gelatinolytic activity induced in HaCat under nickel stimulation.. We analyzed the involvement of protein kinase A (PKA), protein kinase C (PKC), tyrosine kinase (PTK), nuclear factor-kB (NF-kB) and activator protein-1 (AP-1) using specific inhibitors (H89, calphostin C, genistein, carpain and curcumin) by electrophoretic mobility shift assay, reverse transcription-polymerase chain reaction and gelatin zymography.. Our results indicate that nickel-induced MMP-2 production was inhibited with PTK, PKC and AP-1 specific inhibitors. Moreover, both PKA and NF-kB were not involved in nickel pathway.. Using HaCat, we showed that curcumin and genistein can revert nickel-induced MMP-2 upregulation. Whether the use of PTK and AP-1 inhibitors has therapeutic ramifications in the management of ACD remains to be investigated.

Topics: Cell Line, Transformed; Curcumin; Dermatitis, Contact; Drug Combinations; Enzyme Inhibitors; Gene Expression Regulation; Genistein; Humans; Irritants; Keratinocytes; Matrix Metalloproteinase 2; Matrix Metalloproteinase Inhibitors; Nickel; Protein-Tyrosine Kinases; RNA, Messenger; Signal Transduction; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Transcription Factor AP-1; Up-Regulation