Background - cervical carcinoma cells including those infected with the oncogenic human papilloma virus (HPV) and several cervical carcinoma cell lines show a strong expression of the CD40 receptor, unlike benign cervical epithelial cells infected with HPV. The functional relevance of this up-regulated expression in the tumor is not fully understood. Nevertheless, it might offer a unique possibility to target those malignant cells due to the antiviral and antitumoral effects of the CD40/CD40 ligand (CD40L) interactions. Aim - in vitro assessment of the effect of CD40L on HPV 18-P105 promoter activity and the subsequent release of IL-6 by the promoter transfected HeLaCD40 cells, which express CD40 constitutively. Transfection of HeLaCD40 cells was achieved by electroporation after optimizing the parameters by the pCMV-beta-Gal vector and beta-Gal stain. Transfected HeLaCD40 cells were challenged with BHKCD4oL and TNFalpha, in addition to BHKwt, and medium alone as controls. HPV18-P105 promoter activity was demonstrated by luciferase reporter gene assay while IL-6 was assessed by ELISA. CD40/CD40L interactions and TNFalpha treatment significantly reduced HPV18-P105 promoter activity (56,0 +- 10,2 % and 64,1 +- 9,1 % rv. control, respectively; p << 0,001). Likewise, IL-6, which is a sensitive cytokine of CD40 activation, was significantly increased in HeLaCD40 cells in the same experiments (2,7 fold after stimulation with BHKCD40L and 5,2 fold after stimulation with TNFalpha vs. control; p << 0,01 and p << 0,001, respectively). Conclusion: it is likely that the CD40/CD40L interactions and TNFalpha are effective against cervical carcinomas by repressing transcriptional activity of HPV promoter. This can result in new adjuvant treatments.

  Повний текст PDF - 161.226 Kb    Зміст випуску     Цитування публікації

  Якщо, ви не знайшли інформацію про автора(ів) публікації, маєте бажання виправити або відобразити більш докладну інформацію про науковців України запрошуємо заповнити "Анкету науковця"