Effects of Porphyromonas gingivalis and Fusobacterium nucleatum on inflammasomes and their regulators in H400 cells

Abstract

IntroductionInflammasomes are multiprotein complexes that regulate immune processes in response to infections and tissue damage. They modulate Interleukin‐1beta (IL‐1β) expression, a major proinflammatory cytokine. The inflammasome/IL‐1β pathway is involved in head and neck squamous cell carcinoma (HNSCC) progression and the periodontal pathogens Fusobacterium nucleatum (Fn) and Porphyromonas gingivalis (Pg) have been reported to cause chronic inflammation in HNSCC. The aim of this study was to characterise the role of these pathogens in regulating inflammasome activity and the IL‐1β response in HNSCC in vitro.MethodsAn HNSCC cell line (H400) was exposed to Fn and Pg individually or in combination for 24h, ± incubation for 30 min with 5 mM adenosine triphosphate (ATP). Transcript levels of inflammasomes, NLRP3 and AIM2; inflammasome‐regulatory proteins, POP1, CARD16 and TRIM16; and inflammasome‐component, ASC and caspase 1 and IL‐1β, were assayed by RT‐PCR. Expression of IL‐1β was by immunocytochemistry and ELISA.ResultsNLRP3 expression was significantly upregulated in response to Pg, Fn + Pg, Pg + ATP and Fn + Pg + ATP. AIM2 was significantly upregulated by Fn, Pg and Fn + Pg + ATP exposure. All conditions significantly upregulated IL‐1β gene expression. POP1 expression was significantly downregulated by Pg or Fn exposure but not by Fn + Pg. Intracellular pro‐ and mature IL‐1β were significantly higher following Fn and Pg + ATP exposure.ConclusionPg alone increased IL‐1β by upregulating AIM2, NLRP3 and downregulating POP1. Fn promoted IL‐1β by increasing AIM2 and downregulating POP1. Pg + ATP with or without Fn upregulated NLRP3, IL‐1β by downregulating POP1. Periodontal pathogens may contribute to HNSCC pathogenesis by increasing the IL‐1β response due to inflammasome dysregulation.

<p>Alveolar Bone Loss, Tooth Loss and Oral Cancer Mortality in Older Patients: A Retrospective Cohort Study</p>

“…28,29 In particular, oral bacteria including Porphyromonas gingivalis, Fusobacterium nucleatum and Treponema denticola have been recognized as potential etiological agents of oral cancer and recently these pathogens have been found to dysregulate inflammatory mechanisms in oral cancer cells. 30,31 Certain limitations should be considered when interpreting the results of the present study. First, the dietary habits of the subjects were not considered in our study.…”

The cancer metabolic reprogramming and immune response

“…Studies have found that extracellular ATP can activate T cells expressing P2 × 7, inhibit the differentiation and function of regulatory T (Treg) cells, and induce them to differentiate into TH17 cells and promote the production of interleukin-17 (IL-17) in white blood cells [157,158]. Meanwhile, ATP can also promote the activation of NLRP3 inflammasome in phagocytes, thereby releasing a large amount of IL-1 and IL-18, further aggravating the occurrence of inflammation [159]. In fact, extracellular ATP also has a regulatory effect on the functions of CD4 + T cells and Treg cells, and this regulation is concentration-dependent [160].…”

Involvement of Fusobacterium Species in Oral Cancer Progression: A Literature Review Including Other Types of Cancer

“…IL-1β plays a pro-tumorigenic role and enhances the aggressiveness of OSCC [ 66 ]. Aral et al reported that F. nucleatum infection in OSCC cells promotes AIM2 inflammasome expression [ 67 ]. In addition, F. nucleatum potentially upregulated IL-1β expression, but downregulated POP1 which controls NLRP3 inflammasome activation by targeting ASC.…”