Upregulation of interleukin‐1 by Epstein–Barr virus latent membrane protein 1 and its possible role in nasopharyngeal carcinoma cell growth

Huang, Yimin; Tsai, Ching-Hwa; Yeh, Te‐Huei

doi:10.1002/hed.21270

Cited by 13 publications

(10 citation statements)

References 34 publications

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“…Our results showed that pro‐IL‐1β is induced by LMP1 in 4 NPC cell lines, NPC‐TW01, ‐TW02, ‐TW04 and HK1; similar induction was previously reported in NPC‐TW01 (Huang et al, 2010). Since inflammasome‐mediated release of IL‐1β can drive chronic inflammation with protumour activity (Fig 5C; Apte & Voronov, 2008), this might explain why in EBV‐associated cancers, the inflammasome genes are induced and activated by viral factors such as LMP1 and EBERs (Fig 7).…”

Section: Discussionsupporting

confidence: 91%

Tumour inflammasome‐derived IL‐1β recruits neutrophils and improves local recurrence‐free survival in EBV‐induced nasopharyngeal carcinoma

et al. 2012

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Inflammasomes sense infection and cellular damage and are critical for triggering inflammation through IL-1β production. In carcinogenesis, inflammasomes may have contradictory roles through facilitating antitumour immunity and inducing oncogenic factors. Their function in cancer remains poorly characterized. Here we show that the NLRP3, AIM2 and RIG-I inflammasomes are overexpressed in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), and expression levels correlate with patient survival. In tumour cells, AIM2 and RIG-I are required for IL-1β induction by EBV genomic DNA and EBV-encoded small RNAs, respectively, while NLRP3 responds to extracellular ATP and reactive oxygen species. Irradiation and chemotherapy can further activate AIM2 and NLRP3, respectively. In mice, tumour-derived IL-1β inhibits tumour growth and enhances survival through host responses. Mechanistically, IL-1β-mediated anti-tumour effects depend on infiltrated immunostimulatory neutrophils. We show further that presence of tumour-associated neutrophils is significantly associated with better survival in NPC patients. Thus, tumour inflammasomes play a key role in tumour control by recruiting neutrophils, and their expression levels are favourable prognostic markers and promising therapeutic targets in patients.

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Section: Discussionsupporting

confidence: 91%

Tumour inflammasome‐derived IL‐1β recruits neutrophils and improves local recurrence‐free survival in EBV‐induced nasopharyngeal carcinoma

et al. 2012

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“…IL‐1α is one of the major agonistic molecules of IL‐1 family, Oberyszyn et al [23] demonstrated that production of IL‐1α and other inflammatory cytokines induced leucocyte infiltration and resulted in carcinoma formation. The IL‐1α was significantly increased in NPC tissues and was detected in NPC tissues transplanted to nude mice [24, 25], and strong IL‐1α activity also was found in the medium from short‐term‐cultured fresh NPC biopsies [22]. In the NPC microenvironment, the IL‐1α might play an important role in tumor growth or progression [18, 25].…”

Section: Discussionmentioning

confidence: 99%

“…The IL‐1α was significantly increased in NPC tissues and was detected in NPC tissues transplanted to nude mice [24, 25], and strong IL‐1α activity also was found in the medium from short‐term‐cultured fresh NPC biopsies [22]. In the NPC microenvironment, the IL‐1α might play an important role in tumor growth or progression [18, 25]. Previous studies showed that genetic polymorphisms in the coding and promoter region sequences may regulate cytokine secretion.…”

Section: Discussionmentioning

confidence: 99%

Association of IL‐1 polymorphisms and IL‐1 serum levels with susceptibility to nasopharyngeal carcinoma

Yang

Dai

Zhong

et al. 2010

Molecular Carcinogenesis

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Previous studies demonstrated that the polymorphism of interleukin-1 (IL-1) produce alterations of the protein expression and may contribute to oncogenetic processes. The aim of this study was to investigate the relationship between IL-1A gene polymorphisms and NPC susceptibility and the influence of on IL-1α serum levels in cases versus controls. To test whether the genetic variants of IL-1A gene modify the risk of nasopharyngeal carcinoma (NPC), we compared the -889C/T and rs3783553 polymorphisms between 248 patients with NPC and 296 healthy controls using polymerase chain reaction-restriction fragment length polymorphism. Serum IL-1α levels were measured by enzyme-linked immunosorbent assay. The rs3783553 (TTCA insertion or deletion) polymorphism of the IL-1A gene was significantly associated with the susceptibility to NPC. The variant homozygote genotype +/+ was associated with a significantly reduced risk of NPC as compared with the wild homozygote -/- genotype, and the serum IL-1α levels were significantly lower in individuals with homozygous +/+ genotypes. No association was found between the -889C/T polymorphisms and risk of NPC, and no statistically significant differences were found between rs3783553 polymorphism and clinical pathology indices. The IL-1A rs3783553 polymorphism might contribute to a risk of developing NPC by affecting the serum IL-1α secretion in the Chinese population.

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“…NFκB signaling promotes growth and survival of the infected cells [36,92,93]. Through NFκB activation, LMP1 also induces IL-1α, IL-1β, and TNF-α in infected cells, favoring transformation as in the context of NPC development [94,95].…”

Section: Ebv Perturbation Of Prrsmentioning

confidence: 99%

Epstein–Barr Virus and Innate Immunity: Friends or Foes?

et al. 2019

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Epstein–Barr virus (EBV) successfully persists in the vast majority of adults but causes lymphoid and epithelial malignancies in a small fraction of latently infected individuals. Innate immunity is the first-line antiviral defense, which EBV has to evade in favor of its own replication and infection. EBV uses multiple strategies to perturb innate immune signaling pathways activated by Toll-like, RIG-I-like, NOD-like, and AIM2-like receptors as well as cyclic GMP-AMP synthase. EBV also counteracts interferon production and signaling, including TBK1-IRF3 and JAK-STAT pathways. However, activation of innate immunity also triggers pro-inflammatory response and proteolytic cleavage of caspases, both of which exhibit proviral activity under some circumstances. Pathogenic inflammation also contributes to EBV oncogenesis. EBV activates NFκB signaling and induces pro-inflammatory cytokines. Through differential modulation of the proviral and antiviral roles of caspases and other host factors at different stages of infection, EBV usurps cellular programs for death and inflammation to its own benefits. The outcome of EBV infection is governed by a delicate interplay between innate immunity and EBV. A better understanding of this interplay will instruct prevention and intervention of EBV-associated cancers.

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Upregulation of interleukin‐1 by Epstein–Barr virus latent membrane protein 1 and its possible role in nasopharyngeal carcinoma cell growth

Abstract: EBV LMP1 is capable of upregulating IL-1alpha and IL-1beta secretions from epithelial cells and positively modulated by TNF-alpha. This may consequently contribute to tumor growth in patients with NPC.

Cited by 13 publications

References 34 publications

Tumour inflammasome‐derived IL‐1β recruits neutrophils and improves local recurrence‐free survival in EBV‐induced nasopharyngeal carcinoma

Tumour inflammasome‐derived IL‐1β recruits neutrophils and improves local recurrence‐free survival in EBV‐induced nasopharyngeal carcinoma

Association of IL‐1 polymorphisms and IL‐1 serum levels with susceptibility to nasopharyngeal carcinoma

Epstein–Barr Virus and Innate Immunity: Friends or Foes?

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