title: CD40/CD40 ligand interactions and TNFα treatment reduce activity of P105 promoter of the human papilloma virus-18 in vitro.
abstract: 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.
  
  
  OBJECTIVE
  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 HeLa(CD40) cells, which express CD40 constitutively.
  
  
  METHODS
  Transfection of HeLa(CD40) cells was achieved by electroporation after optimizing the parameters by the pCMV-β-Gal vector and β-Gal stain. Transfected HeLa(CD40) cells were challenged with BHK(CD40L) and TNFα, in addition to BHK(wt) and medium alone as controls. HPV18-P105 promoter activity was demonstrated by luciferase reporter gene assay while IL-6 was assessed by ELISA.
  
  
  RESULTS
  CD40/CD40L interactions and TNFα treatment significantly reduced HPV18-P105 promoter activity (56.0 ± 10.2% and 64.1 ± 9.1% vs. control, respectively; p < 0.001). Likewise, IL-6, which is a sensitive cytokine of CD40 activation, was significantly increased in HeLa(CD40) cells in the same experiments (2.7 fold after stimulation with BHK(CD40L) and 5.2 fold after stimulation with TNFα vs. control; p < 0.01 and p < 0.001, respectively).
  
  
  CONCLUSIONS
  It is likely that the CD40/CD40L interactions and TNFα are effective against cervical carcinomas by repressing transcriptional activity of HPV promoter. This can result in new adjuvant treatments.
authors.affiliation: Department of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau D-06847, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Altenburg
authors.affiliation: Department of Dermatology, Ain Shams University, Cairo 11566, Egypt.
authors.forename: M Badawy
authors.initials: MB
authors.lastname: Abdel-Naser
authors.affiliation: Department of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau D-06847, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Nikolakis
authors.affiliation: Department of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau D-06847, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Wild
authors.affiliation: Center of Life Sciences Institute of Bioanalytical Sciences (IBAS), Anhalt University of Applied Sciences, Bernburg D-06406, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Wojtalewicz
mesh_terms: D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D002584:Cervix Uteri / Q000276:immunology / Q000821:virology; D005260:Female; D017930:Genes, Reporter; D006367:HeLa Cells; D052161:Human papillomavirus 18 / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000276:immunology* / Q000821:virology
chemical_list: D019013:CD40 Antigens; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand