Role of inflammasome genetics in susceptibility to HPV infection and cervical cancer development

Pontillo, Alessandra; Bricher, Pamela N.; Leal, Vinícius Nunes Cordeiro; Lima, Salvador Vilar Correia; Souza, Paulo Roberto Eleutério de; Crovella, Sérgio

doi:10.1002/jmv.24514

Cited by 57 publications

(49 citation statements)

References 29 publications

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“…Finally, mature caspase-1 cleaves pro-IL-1β to produce cleaved-IL-1β [14, 30, 31]. Pontillo et al found that NLRP3 inflammasome pathway could affect HPV virus/persistence and cervical cancer progression [32]. Moreover, the findings of Abdul-Sater et al demonstrated that NLRP3-dependent caspase-1 activation in cervical epithelial cells contributes to development of the chlamydial inclusion and cervical cancer progression [33].…”

Section: Discussionmentioning

confidence: 99%

CD200Fc reduces LPS-induced IL-1β activation in human cervical cancer cells by modulating TLR4-NF-κB and NLRP3 inflammasome pathway

Shao

Zhang

et al. 2017

Oncotarget

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Chronic inflammation plays an important role in tumorigenesis of cervical cancer. CD200Fc, a CD200R1 agonist, has been found to have anti-inflammatory effects in autoimmune diseases and neuro-degeneration. However, the anti-inflammatory effect of CD200Fc on cervical cancer has not yet to be completely understood. This study investigated the anti-inflammatory effects and mechanisms of CD200Fc in LPS-induced human SiHa cells and Caski cells. SiHa cells and Caski cells were stimulated with 40 μg/ml LPS under different concentrations of CD200Fc for 90 min or 12 hours. The mRNA and protein levels of pro-IL-1β, cleaved-IL-1β and NLRP3, as well as the protein level of cleaved caspase-1, were significantly increased in LPS-induced SiHa cells and Caski cells. LPS stimulation did not change ASC and pro-caspase-1 expression. CD200Fc down-regulated protein expression of cleaved caspase-1 and mRNA and protein expression of pro-IL-1β, cleaved-IL-1β and NLRP3. In addition, the protein levels of TLR4, p-P65 and p-IκB, as well as the translocation of P65 to nucleus, were significantly increased in LPS-induced SiHa cells and Caski cells. LPS stimulation did not change t-P65 and t-IκB on protein levels, which were components of TLR-NF-κB pathway. CD200Fc down-regulated protein expression of TLR4, p-P65 and p-IκB and inhibited the translocation of P65 to nucleus in LPS-induced SiHa cells and Caski cells. These results indicated that CD200Fc appeared to suppress the inflammatory activity of TLR4-NF-κB and NLRP3 inflammasome pathway in LPS-induced SiHa cells and Caski cells. It provided novel mechanistic insights into the potential therapeutic uses of CD200Fc for cervical cancer.

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Section: Discussionmentioning

confidence: 99%

CD200Fc reduces LPS-induced IL-1β activation in human cervical cancer cells by modulating TLR4-NF-κB and NLRP3 inflammasome pathway

Shao

Zhang

et al. 2017

Oncotarget

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“…IL-1β rs-1143643, NLRP1 rs-11651270, NLRP3 rs-10754558, and IL-18 rs-1834481 are associated with protection against persistent human papillomavirus (HPV) infection or HPV-related cervical cancer (144). It further validates anticancer effects of inflammasomes in a genetic perspective.…”

Section: Inflammasome Inflammation and Cancermentioning

confidence: 99%

Inflammasomes in Inflammation-Induced Cancer

Lin

Zhang

2017

Front. Immunol.

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The inflammasome is an important multiprotein complex that functions during inflammatory immune responses. The activation of inflammasome will lead to the autoactivation of caspase-1 and subsequent cleavage of proIL-1β and proIL-18, which are key sources of inflammatory manifestations. Recently, the roles of inflammasomes in cancers have been extensively explored, especially in inflammation-induced cancers. In different and specific contexts, inflammasomes exhibit distinct and even contrasting effects in cancer development. In some cases, inflammasomes initiate carcinogenesis through the extrinsic pathway and maintain the malignant cancer microenvironment through the intrinsic pathway. On the contrary, inflammasomes also exert anticancer effects by specialized programmed cell death called pyroptosis and immune regulatory functions. The phases and compartments in which inflammasomes are activated strongly influence the final immune effects. We systemically summarize the functions of inflammasomes in inflammation-induced cancers, especially in gastrointestinal and skin cancers. Besides, information about the current therapeutic use of inflammasome-related products and potential future developing directions are also introduced.

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“…ROS regulates inflammasomes in response to oncogenic viral infections [10, 13, 14]. Inflammasomes are important component of the innate immune system that are recruited to a damaged site to facilitate tissue repair.…”

Section: Oncogenic Virus-induced Reactive Oxygen Species and Dna Dmentioning

confidence: 99%

“…Activation of HPV16-mediated AIM2 inflammasomes and upregulation of the proinflammatory cytokines IL-1 β , IL-1 α , and IL-18 were found to significantly increase cervical cancer progression in cervical lesions [14]. Interestingly, several single nucleotide polymorphisms (IL-1 β rs1143643, IL-18 rs1834481, NLRP1 rs11651270, and NLRP3 rs10754558) are associated with protection against HPV infection, suggesting the important role of inflammasomes in oncovirus pathogenesis [13]. …”

Section: Human Papillomavirus-induced Carcinogenesismentioning

confidence: 99%

DNA Oncogenic Virus‐Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations

Kgatle

Spearman

Kalla

et al. 2017

Oxidative Medicine and Cellular Longevity

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Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus (EBV). Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations. Accumulation of epigenetic alterations may interfere with genome-wide cellular signalling machineries and promote malignant transformation leading to cancer development. Untangling and understanding the underlying mechanisms that promote these detrimental effects remain the major objectives for ongoing research and hope for effective virus-induced cancer therapy. Here, we review current literature with an emphasis on how DNA damage influences HPV, HVB, and EBV replication and epigenetic alterations that are associated with carcinogenesis.

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Role of inflammasome genetics in susceptibility to HPV infection and cervical cancer development

Abstract: Our findings for the first time demonstrated that inflammasome genetics could affect HPV/host interaction in terms of virus susceptibility as well as of virus/persistence and cervical cancer progression. J. Med. Virol. 88:1646-1651, 2016. © 2016 Wiley Periodicals, Inc.

Cited by 57 publications

References 29 publications

CD200Fc reduces LPS-induced IL-1β activation in human cervical cancer cells by modulating TLR4-NF-κB and NLRP3 inflammasome pathway

CD200Fc reduces LPS-induced IL-1β activation in human cervical cancer cells by modulating TLR4-NF-κB and NLRP3 inflammasome pathway

Inflammasomes in Inflammation-Induced Cancer

DNA Oncogenic Virus‐Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations

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