科研之友
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摘要
TNF-alpha is known to exert antitumor and antiviral effects and to participate in the regulation of the immune response. In our study we demonstrate that human rTNF-alpha specifically blocks growth of SK-v keratinocyte cell line harboring and expressing human papillomavirus type 16 (HPV16) sequences. This inhibitory effect was shown by [H-3]TdR incorporation and cell counting. Binding experiments with I-125-TNF-alpha showed that SK-v cells express about 10,000 single class TNF-alphaR per cell with affinity constant of about 0.7 nM. Binding of I-125-TNF-alpha could be inhibited by htr-9 mAb recognizing a 55/60-kDa type I TNF-alphaR but not by utr-1 mAb recognizing 75/80-kDa type II TNF-alphaR or irrelevant mAb specific for HPV16 E7 protein. Addition of anti-TNF-alpha antibodies to SK-v cell culture resulted in significant (p < 0.05), dose-dependent stimulation of their proliferation. SK-v cells constitutively expressed TNF-alpha mRNA, and SK-v CM contained TNF-alpha, as demonstrated by Northern blot analysis, a specific ELISA, Western blot analysis, and a bioassay with TNF-alpha-sensitive L-M cells. HPLC gel filtration of SK-v cell CM showed that the factor cytotoxic for L-M cells coeluted with immunoreactive TNF-alpha. These results demonstrate that HPV16-harboring SK-v cells constitutively express and release immunoreactive and biologically active TNF-alpha that in turn may exert an autocrine growth inhibitory effect. This phenomenon could represent one of the self-limiting mechanisms controling growth of HPV-induced neoplasia.
- 出版日期1992-10-15
