Involvement of P2Y11 receptor in silica nanoparticles 30-induced IL-6 production by human keratinocytes.

We have previously reported that P2Y11 receptor mediates IFN-γ-induced IL-6 production in human keratinocytes, suggesting the importance of purinergic signaling in skin inflammatory diseases. In this study, the involvement of various P2 receptors in IL-6 production induced by silica nanoparticle 30 (SNP30) was examined in a human keratinocyte cell line, HaCaT. Exposure to SNP30 increased IL-6 production in the cells. Ecto-nucleotidase (apyrase), a non-selective antagonist of P2Y receptors (suramin), and a selective P2Y11 receptor antagonist (NF157) all inhibited IL-6 production. Nucleotides such as ATP and UTP themselves also significantly increased IL-6 production in the cells. It was further confirmed that ATP was released from HaCaT cells exposed to SNP30. These results support the possible role of ATP in SNP30-induced IL-6 production by HaCaT cells. In conclusion, these data demonstrate that P2Y11 receptor also mediates SNP30-induced IL-6 production in human keratinocytes, confirming that the ATP-P2Y11 purinergic signaling is a common pathway of IL-6 production leading to induction of skin inflammatory diseases.