Inflammasome dysregulation in human gingival fibroblasts in response to periodontal pathogens. (2nd February 2021)

• Record Type: Journal Article
• Authors: Aral, Kübra; Milward, Michael R.; Cooper, Paul R.
• Is Part Of: Oral diseases. Volume 28:Number 1(2022)
• Page Start: 216
• Page End: 224
• Publication Date: 2021-02-02
• Subjects: Fusobacterium nucleatum -- gingival fibroblasts -- inflammasome -- interleukin‐1 beta -- periodontal disease -- Porphyromonas gingivalis; Mouth -- Diseases -- Research -- Periodicals; 617.522
• DOI: 10.1111/odi.13760
• Languages: English
• ISSNs: 1354-523X

Abstract

Abstract: Objective: Uncontrolled production of Interleukin‐1β (IL‐1β), a major proinflammatory cytokine, is associated with tissue destruction in periodontal disease. IL‐1β production is controlled by inflammasomes which are multiprotein regulatory complexes. The current study aimed to elucidate potential regulatory pathways by monitoring the effects of periodontal pathogens Fusobacterium nucleatum ( Fn ) and Porphyromonas gingivalis ( Pg) on inflammasomes and their regulators in human gingival fibroblasts (HGFs) in vitro. Methods: HGFs were exposed to Fn and Pg alone or in combination for 24 hr at a multiplicity of infection of 100, ±30 min exposure with 5 mM adenosine triphosphate (ATP) incubation. Gene expression of NLRP3 and AIM2, inflammasome regulatory proteins POP1, CARD16 and TRIM16, and inflammasome components ASC and CASPASE 1, and IL‐1β, were evaluated by RT‐PCR. Pro‐ and mature IL‐1β levels were monitored intracellularly by immunocytochemistry and extracellularly by ELISA. Results: Fn + ATP significantly upregulated NLRP3, AIM2, IL‐1β, ASC, and CASPASE 1; however, it downregulated POP1 and TRIM16. Pg + ATP downregulated NLRP3, ASC, POP1, but upregulated IL‐1β and CARD16. Pg + Fn+ATP significantly upregulated AIM2, IL‐1β and CARD16, and downregulated POP1, TRIM16, and CASPASE 1. Pg + ATP exposure significantly increased pro‐ and mature IL‐1β production. Conclusion: Bacterial exposure with ATP may deregulate IL‐1β by dysregulating inflammasomes and their regulators in HGFs.