E6 and E7 of human papillomavirus type 18 and <scp>UVB</scp> irradiation corporately regulate interleukin‐6 and interleukin‐8 expressions in basal cell carcinoma

Hsiao, Yu‐Ping; Yang, Jen‐Hung; Wu, Wenjun; Lin, Meng-Hsuan; Sheu, Gwo‐Tarng

doi:10.1111/exd.12223

Cited by 8 publications

(4 citation statements)

References 30 publications

(42 reference statements)

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“…UV-induced oxidative stress affects the generation/activation of both the signaling molecules associated with the kinase signaling cascade and the transcription factors such as Nrf2 that induce the biosynthesis of new proteins responsible for cell protection against DNA mutations, metabolic disorders, and apoptosis [3,10]. UV radiation also affects the cells' defense response via the modification of inflammatory protein mediators such as TNFa and interleukins [3,11].…”

Section: Introductionmentioning

confidence: 99%

Proteins involved in the antioxidant and inflammatory response in rutin-treated human skin fibroblasts exposed to UVA or UVB irradiation

Gęgotek

Domingues

Skrzydlewska

2018

Journal of Dermatological Science

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Section: Introductionmentioning

confidence: 99%

Proteins involved in the antioxidant and inflammatory response in rutin-treated human skin fibroblasts exposed to UVA or UVB irradiation

Gęgotek

Domingues

Skrzydlewska

2018

Journal of Dermatological Science

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“…An increase was observed in IL-6 secretion in studies conducted on cervical cells and other tissues infected with high-risk HPV subtypes. This increase in production and secretion, as in the case of IL-8, is made up of two direct and indirect routes, which were mediated by IL-17 (Hsiao et al, 2013;Ren et al, 2013). The serum or extracellular levels of IL-6 and IL-8 vary under various conditions.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Cervical Levels of Interleukins-6 and -8 in Patients with and without Cervical Intraepithelial Neoplasia

Vahedpour

Abedzadeh-Kalahroudi

Sehat

et al. 2021

Asian Pac J Cancer Prev

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Introduction: Interleukins-6 and -8 are two pro-inflammatory cytokines increasing in serum and local levels under malignant conditions. There are limited evidences on the association between cervical level of these two factors and cervical intraepithelial neoplasia (CIN). So, this study aimed to explore the association between cervical levels of IL-6 and IL-8 with cervical premalignant lesions. Methods: The present case-control study was conducted on married women undergone Pap smear for routine screening in two groups as the group with CIN (n=100) and the healthy control group (n=100). Cervical secretions were collected using sterile swab and the levels of IL-8 and IL-6 were measured by enzymelinked immunosorbent assay (ELISA). The obtained data were analyzed by SPSS software. Results: The mean cervical IL-6 level was 568.66±594.62 pg/ml in the patients with CIN and 212.7±213.9 pg/ml in the controls (P <0.001). The cervical IL-8 levels in the case and control groups were measured to be 1320.43±876.5 pg/ml and 1053.59±747.64 pg/ ml, respectively (p=0.02). By modifying the confounding size effect of the age and marital duration, it was determined that cervical levels of IL-6 and IL-8 were both associated with CIN. Conclusion: Our results showed that the cervical levels of IL-6 and IL-8 are associated with CIN independent of age and marital duration.

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“…Cheng et al have observed an up-regulatory effect of HPV16 and HPV18 E6 and E7 to IL-6 expression in E6 and E7 transfected lung cancer cells (33). Also, the repression of HPV18 E6 and E7 in basal cell carcinoma cells reduced IL-6 expression levels (34). In addition, Dell'Oste et al reported an increase in IL-6 mRNA expression and protein secretion in primary keratinocytes immortalized with both E6E7 genes from HPV16 compared to control keratinocytes (20).…”

Section: Discussionmentioning

confidence: 99%

E6/E7 and E6* From HPV16 and HPV18 Upregulate IL-6 Expression Independently of p53 in Keratinocytes

et al. 2019

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Keratinocyte infection with high-risk human papillomavirus genotypes has been linked to cancer development. In cervix, the alpha HPV16 and HPV18 have been reported as the mayor causative agents of cervical cancer. Oncogenic progression and chronic inflammation are closely related processes, with IL-6 as one of the main pro-inflammatory cytokines involved. However, there are limited studies about the regulation of IL-6 by low and high risk HPVs and the HPV proteins implicated in this modulation. In this work, we report the overexpression of IL-6 in HPV infected cervical cancer derived cell lines (HeLa and SiHa) compared to non-tumorigenic keratinocytes (HaCaT), and in Cervical Intraepithelial Neoplasia grade 1 HPV16 and HPV18 positive cervical samples compared to HPV negative samples without lesions. Moreover, we generated HaCaT keratinocytes that express E5, E6, and E7 from high risk (16 or 18) or low risk (62 and 84) HPVs. E5 proteins do not modify IL-6 expression, while E7 modestly increase it. Interestingly, E6 proteins in HaCaT cells upregulate IL-6 mRNA expression and protein secretion. Indeed, in HaCaT cells that express high risk HPV16E6 or HPV18E6 proteins, only the truncated E6 * isoforms were expressed, showing the stronger IL-6 overexpression, while in HaCaT cells that express low risk HPV62 and HPV84 full length E6 proteins, IL-6 was also upregulated but not so drastically. Since HaCaT cells have a mutated p53 form that is not degraded by the introduction of E6 or E6/E7, it seems that E6/E7 regulate IL-6 by an additional mechanism independent of p53. In addition, basal keratinocytes showed a strong expression of IL-6R using immunohistochemistry, suggesting an autocrine mechanism over proliferative cells. Altogether, IL-6 cytokine expression in keratinocytes is upregulated by E6 and E7 proteins from HPVs 16, 18, 62, and 84, especially by high risk HPV16 and HPV18 E6 * , which may contribute to promote a pro-inflammatory and highly proliferative microenvironment that can persist over time and lead to cervical tumorigenesis.

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E6 and E7 of human papillomavirus type 18 and UVB irradiation corporately regulate interleukin‐6 and interleukin‐8 expressions in basal cell carcinoma

Cited by 8 publications

References 30 publications

Proteins involved in the antioxidant and inflammatory response in rutin-treated human skin fibroblasts exposed to UVA or UVB irradiation

Proteins involved in the antioxidant and inflammatory response in rutin-treated human skin fibroblasts exposed to UVA or UVB irradiation

Comparison of Cervical Levels of Interleukins-6 and -8 in Patients with and without Cervical Intraepithelial Neoplasia

E6/E7 and E6* From HPV16 and HPV18 Upregulate IL-6 Expression Independently of p53 in Keratinocytes

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