Work

Inhibition of BTK and SYK attenuates Porphyromonas gingivalis -induced activation of the pyroptosis pathway and inflammation in host cells

Year: 2025

Type: article

Abstract: Background Periodontitisis a chronic inflammatory disease of the oral cavity, primarily driven by periodontopathogens such as Porphyromonas gingivalis (Pg)."Objective We investigated the therapeutic potential of BTK and SYK inhibitors on the pathological processes induced by two Pg strains, ATCC 33277 and W83, in human monocyte-derived macrophages (hMDMs) and human gingival fibroblasts (hGFs).Design hMDM and hGF were infected with Pg strains and assessed for viability, inflammatory activation, and phenotype, with or without the BTK inhibitor ibrutinib or SYK inhibitor R406, under acute and chronic infection conditions.Results Ibrutinib and R406 suppressed Pg infection-induced activation of the NLRP3-dependent pyroptosis pathway and IL-1β secretion in hMDMs. Both compounds also significantly reduced IL-6, IL-8, and TNFα release by hMDM in both infection models, regardless of differences between ATCC 33277 and W83 Pg strains. Ibrutinib and R406 potently suppressed inflammatory activation of hGFs, including IL-6 and IL-8 production, and NF-κB p65 phosphorylation triggered by the more immunostimulatory ATCC 33277 strain.Conclusions The pharmacological inhibition of BTK or SYK mitigates the pyroptotic pathway in hMDMs and exerts a broad anti-inflammatory effect in both hMDMs and hGFs. These results highlight the anti-inflammatory potential of BTK and SYK inhibitors for the treatment of periodontal disease.

Source: Journal of Oral Microbiology

DOI: 10.1080/20002297.2025.2577219