Interleukin-1 regulates interleukin-6 secretion in human oral squamous cell carcinoma in vitro: possible influence of p53 but not human papillomavirus E6/E7.
Interleukin-1 regulates interleukin-6 secretion in human oral squamous cell carcinoma in vitro: possible influence of p53 but not human papillomavirus E6/E7.
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发表时间：
1998-07
期刊：
影响因子：
11.2
通讯作者：
K. V. Woods;K. Adler‐Storthz;Gary L. Clayman;Gail M. Francis;Elizabeth A. Grimm
中科院分区：
文献类型：
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作者：
K. V. Woods;K. Adler‐Storthz;Gary L. Clayman;Gail M. Francis;Elizabeth A. Grimm
我们之前已经证明，白细胞介素-1 （IL-1）和IL-6是由人口腔鳞状细胞癌（SCC）和一些衍生细胞系组成的，但不是由培养的正常口腔角质形成细胞产生的。为了阐明可能促进口腔鳞状细胞癌生长和/或进展的细胞因子调节途径，我们在体外测试了外源性和/或内源性IL-1调节IL-6产生的假设。我们研究了外源性IL-1和IL-6对次生细胞因子分泌的影响。我们的研究表明，IL-1在所有三种细胞系中都能强烈上调IL-6蛋白的分泌。这种作用被IL-1受体拮抗剂完全消除。IL-1受体拮抗剂也抑制了三种细胞系中两种细胞IL-1 α和IL-1 β的分泌。这些数据首次显示IL-1强烈上调IL-6，并支持IL-1在某些口腔SCC细胞系中自分泌调节的概念。此外，由于人乳头瘤病毒（HPV）感染和p53突变与SCC的恶性转化有关，我们探索了第二种假设，即HPV和/或p53突变有助于细胞因子失调。我们研究了HPV DNA的存在，HPV E6/E7的转录激活（在HPV DNA阳性的细胞系中），以及我们细胞系中p53基因的状态。HPV DNA与细胞因子表达无相关性。然而，分泌IL-6最多的口腔SCC细胞系是突变型而不是野生型p53。
We have previously shown that interleukin-1 (IL-1) and IL-6 are constitutively 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 exogenous and/or endogenous IL-1 regulates IL-6 production in vitro. We investigated the effects of exogenous IL-1 and IL-6 on secondary cytokine secretion. Our studies revealed that IL-1 strongly up-regulated IL-6 protein secretion in all three cell lines tested. This effect was completely abrogated by IL-1 receptor antagonist. IL-1 receptor antagonist also inhibited the secretion of IL-1alpha and IL-1beta in two of three cell lines. These data show for the first time that IL-1 strongly up-regulates IL-6 and support the notion of autocrine regulation of IL-1 in certain oral SCC cell lines. Additionally, because human papillomavirus (HPV) infection and p53 mutation have been implicated in the malignant transformation of SCC, we explored a second hypothesis, that HPV and/or p53 mutation contribute to cytokine dis-regulation. We investigated 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. However, the oral SCC cell lines secreting the most IL-6 had mutant rather than wild-type p53.