Study on the mechanism of chemokine release from mast cells by environmental chemicals

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The effect of the anti-oxidant and Ca^<2+> ATPase inhibitor, 2,5-di-(tert-butyl)-1, 4-hydroquinone (DTBHQ), on the release of MCP-1 from RBL-2H3 and bone marrow-derived mast cells (BMMCs) were investigated. DTBHQ increased the intracellular free Ca^<2+> concentration and induced MCP- 1 release in a dose-dependent manner. It was inhibited by treatment with actinomycin D, cyclosporin A, and p38 MAP kinase inhibitor SB202190. Furthermore, RT-PCR showed a time-dependent increase of MCP-1 mRNA. Thus MCP-1 release seems to depend on Ca^<2+>-dependent transcriptional activation. Next, the mRNA expression profiles (8,799 genes) of RBL-2H3 cells activated by 10μM DTBHQ were analyzed with GeneChip arrays. The genes, including MCP-1, GADD45, Relaxin HI, IL-3, IL-4, IL-9, IL-13, GADD153, were significantly up-regulated by DTBHQ. These results suggest that DTBHQ seems to induce proinflammatory responses by stimulating the production of chemokine and several cytokines through the expression of several transcription factors.