In the progress of a carcinogenetic process, the promoter effect was seen as the final event able to determine uncontrolled proliferation. The promoter effect begins with an inhibition of gap junctional intercellular communication. Previously we observed an inhibitory effect of Mercury (HgCl2) on Gap Junction Intercellular Communication of Human Keratinocytes in culture. Here we evaluate the effect of Mercury on gap junctional intercellular communication, on cytokines intracellular concentrations and on cytokines secretion of Human Keratinocytes. In particular, we report a reduction of the intracellular concentrations and secretions of Tumour Necrosis alpha and Interleukin 1 beta. It is known that the inhibitory effect on Gap Junctional Intercellular Communication is correlated with a promoter effect induced by carcinogens. In this paper we discuss the relationship between the inhibition of gap junctional intercellular communication and cytokine production, and whether these effects are related in an xenobiotic carcinogenesis process. Our considerations could be seen as too adventurous, but they may set the stage for an open discussion of our results according to the literature. An intriguing relationship appears to develop when comparing the effects of proinflammatory mediators on GJIC. Although highly speculative, a review of the current literature would suggest that the GJIC inhibition induced by mercury might be the beginning of the promoter effect, but the role induced by cytokines on initiated cells to stimulate its proliferation remains to be determined We think that the reduction of TNF-alpha, and in part IL-1beta, induced by mercury might favour the cancer. We hypothesise that the reduction of cytokines and inhibition of the gap junction intercellular communication are correlated and they may play a role in the xenobiotic carcinogenesis process.
|Number of pages||6|
|Journal||International Journal of Immunopathology and Pharmacology|
|Issue number||4 Suppl|
|Publication status||Published - Oct 2006|
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