CD40/CD40 ligand interactions and TNFα treatment reduce activity of P105 promoter of the human papilloma virus-18 in vitro

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-regulat...

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Дата:2016
Автори: Altenburg, A., Abdel-Naser, M.B., Nikolakis, G., Wild, T., Wojtalewicz, N.
Формат: Стаття
Мова:English
Опубліковано: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2016
Назва видання:Experimental Oncology
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Онлайн доступ:http://dspace.nbuv.gov.ua/handle/123456789/137979
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Назва журналу:Digital Library of Periodicals of National Academy of Sciences of Ukraine
Цитувати:CD40/CD40 ligand interactions and TNFα treatment reduce activity of P105 promoter of the human papilloma virus-18 in vitro / A. Altenburg, M.B. Abdel-Naser, G. Nikolakis, T. Wild, N. Wojtalewicz // Experimental Oncology. — 2016 — Т. 38, № 1. — С. 22-25. — Бібліогр.: 24 назв. — англ.

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Digital Library of Periodicals of National Academy of Sciences of Ukraine
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spelling irk-123456789-1379792018-06-18T03:03:41Z CD40/CD40 ligand interactions and TNFα treatment reduce activity of P105 promoter of the human papilloma virus-18 in vitro Altenburg, A. Abdel-Naser, M.B. Nikolakis, G. Wild, T. Wojtalewicz, N. Original contributions 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. Material and Methods: Transfection of HeLaCD₄₀ cells was achieved by electroporation after optimizing the parameters by the pCMV-β-Gal vector and β-Gal stain. Transfected HeLaCD₄₀ cells were challenged with BHKCD40L and TNFα, in addition to BHKwt and medium alone as controls. HPV18P105 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 HeLaCD₄₀ cells in the same experiments (2.7 fold after stimulation with BHKCD₄₀L and 5.2 fold after stimulation with TNFα vs. control; p < 0.01 and p < 0.001, respectively). Conclusion: 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. 2016 Article CD40/CD40 ligand interactions and TNFα treatment reduce activity of P105 promoter of the human papilloma virus-18 in vitro / A. Altenburg, M.B. Abdel-Naser, G. Nikolakis, T. Wild, N. Wojtalewicz // Experimental Oncology. — 2016 — Т. 38, № 1. — С. 22-25. — Бібліогр.: 24 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/137979 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
language English
topic Original contributions
Original contributions
spellingShingle Original contributions
Original contributions
Altenburg, A.
Abdel-Naser, M.B.
Nikolakis, G.
Wild, T.
Wojtalewicz, N.
CD40/CD40 ligand interactions and TNFα treatment reduce activity of P105 promoter of the human papilloma virus-18 in vitro
Experimental Oncology
description 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. Material and Methods: Transfection of HeLaCD₄₀ cells was achieved by electroporation after optimizing the parameters by the pCMV-β-Gal vector and β-Gal stain. Transfected HeLaCD₄₀ cells were challenged with BHKCD40L and TNFα, in addition to BHKwt and medium alone as controls. HPV18P105 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 HeLaCD₄₀ cells in the same experiments (2.7 fold after stimulation with BHKCD₄₀L and 5.2 fold after stimulation with TNFα vs. control; p < 0.01 and p < 0.001, respectively). Conclusion: 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.
format Article
author Altenburg, A.
Abdel-Naser, M.B.
Nikolakis, G.
Wild, T.
Wojtalewicz, N.
author_facet Altenburg, A.
Abdel-Naser, M.B.
Nikolakis, G.
Wild, T.
Wojtalewicz, N.
author_sort Altenburg, A.
title CD40/CD40 ligand interactions and TNFα treatment reduce activity of P105 promoter of the human papilloma virus-18 in vitro
title_short CD40/CD40 ligand interactions and TNFα treatment reduce activity of P105 promoter of the human papilloma virus-18 in vitro
title_full CD40/CD40 ligand interactions and TNFα treatment reduce activity of P105 promoter of the human papilloma virus-18 in vitro
title_fullStr CD40/CD40 ligand interactions and TNFα treatment reduce activity of P105 promoter of the human papilloma virus-18 in vitro
title_full_unstemmed CD40/CD40 ligand interactions and TNFα treatment reduce activity of P105 promoter of the human papilloma virus-18 in vitro
title_sort cd40/cd40 ligand interactions and tnfα treatment reduce activity of p105 promoter of the human papilloma virus-18 in vitro
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
publishDate 2016
topic_facet Original contributions
url http://dspace.nbuv.gov.ua/handle/123456789/137979
citation_txt CD40/CD40 ligand interactions and TNFα treatment reduce activity of P105 promoter of the human papilloma virus-18 in vitro / A. Altenburg, M.B. Abdel-Naser, G. Nikolakis, T. Wild, N. Wojtalewicz // Experimental Oncology. — 2016 — Т. 38, № 1. — С. 22-25. — Бібліогр.: 24 назв. — англ.
series Experimental Oncology
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first_indexed 2023-10-18T21:14:20Z
last_indexed 2023-10-18T21:14:20Z
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