INTERLEUKIN-1 REGULATES INTERLEUKIN-6 SECRETION IN HUMAN ORAL SQUAMOUS-CELL CARCINOMA IN-VITRO - POSSIBLE INFLUENCE OF P53 BUT NOT HUMAN-PAPILLOMAVIRUS E6 E7/

We have previously shown that interleukin-1 (IL-1) and IL-6 are consti tutively produced by human oral squamous cell carcinoma (SCC) and some derived cell lines but not by cultured normal oral keratinocytes. To elucidate possible cytokine regulatory pathways that may contribute to oral SCC growth and/or progression, we tested the hypotheses that exo genous and/or endogenous IL-1 regulates IL-6 production in vitro, We i nvestigated the effects of exogenous IL-1 and IL-6 on secondary cytoki ne secretion. Our studies revealed that IL-1 strongly up-regulated IL- 6 protein secretion in all three cell lines tested. This effect was co mpletely abrogated by IL-1 receptor antagonist. IL-1 receptor antagoni st also inhibited the secretion of IL-1 alpha and IL-1 beta in two of three cell lines. These data show for the first time that IL-1 strongl y up-regulates IL-6 and support the notion of autocrine regulation of IL-1 in certain oral SCC cell lines, Additionally, because human papil lomavirus (HPV) infection and p53 mutation have been implicated in the malignant transformation of SCC, we explored a second hypothesis, tha t HPV and/or p53 mutation contribute to cytokine dis-regulation, We in vestigated HPV DNA presence, transcriptional activation of HPV E6/E7 ( in HPV DNA-positive cell lines), and p53 gene status in our cell lines . No association between HPV DNA and cytokine expression was found. Ho wever, the oral SCC cell lines secreting the most IL-6 had mutant rath er than wild-type p53.