Interferon‐Gamma and Fas Are Involved in Porphyromonas gingivalis–Induced Apoptosis of Human Extravillous Trophoblast‐Derived HTR8/SVneo Cells via Extracellular Signal‐Regulated Kinase 1/2 Pathway

Background: A number of studies recently revealed a link between periodontal disease and preterm birth (PTB). PTB can be induced by dental infection with Porphyromonas gingivalis (Pg), a periodontopathic bacterium. This study aims to investigate responses of human extravillous trophoblast‐derived HTR8/SVneo cells to Pg infection. Methods: Cell apoptosis, cell viability, protein expression, and cytokine production in HTR8 cells were measured via: 1) flow cytometry, 2) CCK‐8 assay, 3) western blot, and 4) enzyme‐linked immunosorbent assay methods, respectively. Results: Pg decreased cell viability and increased cell apoptosis, active caspase‐3 and Fas expression, and interferon‐gamma (IFN‐γ) secretion in HTR8 cells. Extracellular signal‐regulated kinase (ERK) 1/2 inhibitor U0126 and FasL neutralizing antibody NOK1 that blocks FasL/Fas interaction both significantly suppressed Pg‐induced apoptosis. U0126 also inhibited IFN‐γ secretion and Fas expression close to control levels. Moreover, treatment with recombinant IFN‐γ also significantly decreased number of viable HTR8 cells and increased Fas expression, suggesting IFN‐γ may play an important role in Pg‐induced apoptosis of HTR8 cells, at least partially through regulation of Fas expression. Conclusions: To the best of the authors’ knowledge, this is the first study to demonstrate Pg induces IFN‐γ secretion, Fas expression, and apoptosis in human extravillous trophoblast‐derived HTR8/SVneo cells in an ERK1/2‐dependent manner, and IFN‐γ (explored by recombinant IFN‐γ) and Fas are involved in Pg‐induced apoptosis. The finding that Pg infection abnormally regulates inflammation and apoptosis of human trophoblasts may give new insights into the possible link of PTB with maternal periodontal disease and periodontal pathogens.