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 |
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Формат: | Стаття |
Мова: | English |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2016
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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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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 |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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DSpace DC |
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English |
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Original contributions Original contributions |
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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 |
work_keys_str_mv |
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first_indexed |
2023-10-18T21:14:20Z |
last_indexed |
2023-10-18T21:14:20Z |
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