Porphyromonas gingivalis differentially modulates apoptosome APAF-1 in epithelial cells and fibroblasts.

In this study, Apaf-1 and X-linked inhibitor of apoptosis protein (Xiap) mRNA were differentially expressed between gingival samples harvested from human healthy and chronic periodontitis tissues (Apaf-1: 19.2-fold; caspase-9: 14.5-fold; caspase-3: 6.8-fold; Xiap: 2.5-fold in chronic periodontitis) (P < 0.05)), highlighting their potential role in periodontitis. An increased proteic expression of APAF-1 was also observed in a murine experimental periodontitis model induced by P.gingivalis-soaked ligatures. In vitro, it was observed that P.gingivalis targets apoptosome-related pathways, including APAF-1, XIAP, caspase-3, and caspase-9, to inhibit epithelial cell death at both mRNA and protein levels. Opposite effect was observed in fibroblasts where P.gingivalis increased cell mortality and apoptosis. To assess if the observed effects were associated to APAF-1, epithelial cells and fibroblasts were transfected with siRNA targeting Apaf-1. Herein, we confirmed that APAF-1 is targeted by P.gingivalis in both cell types. Taken together, this study identified APAF-1 apoptosome and XIAP as intra-cellular targets of P.gingivalis, contributing to the deterioration of periodontal lesion through an increased persistence of the bacteria within tissues and the subversion of host-response.
PMID: 29154960 [PubMed - as supplied by publisher]

Source: The American Journal of Pathology - November 15, 2017 Category: Pathology Authors: Bugueno IM, Batool F, Korah L, Benkirane-Jessel N, Huck O Tags: Am J Pathol Source Type: research