Porphyromonas Gingivalis Gingipain-Dependently Enhances IL-33 Production in Human Gingival Epithelial Cells

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Apr 9

PMID 27058037

Citations 24

Authors

Hiroyuki Tada

Takashi Matsuyama

Takashi Nishioka

Makoto Hagiwara

Yusuke Kiyoura

Hidetoshi Shimauchi

Kenji Matsushita

Affiliations

Soon will be listed here.

Abstract

The cytokine IL-33 is constitutively expressed in epithelial cells and it augments Th2 cytokine-mediated inflammatory responses by regulating innate immune cells. We aimed to determine the role of the periodontal pathogen, Porphyromonas gingivalis, in the enhanced expression of IL-33 in human gingival epithelial cells. We detected IL-33 in inflamed gingival epithelium from patients with chronic periodontitis, and found that P. gingivalis increased IL-33 expression in the cytoplasm of human gingival epithelial cells in vitro. In contrast, lipopolysaccharide, lipopeptide, and fimbriae derived from P. gingivalis did not increase IL-33 expression. Specific inhibitors of P. gingivalis proteases (gingipains) suppressed IL-33 mRNA induction by P. gingivalis and the P. gingivalis gingipain-null mutant KDP136 did not induce IL-33 expression. A small interfering RNA for protease-activated receptor-2 (PAR-2) as well as inhibitors of phospholipase C, p38 and NF-κB inhibited the expression of IL-33 induced by P. gingivalis. These results indicate that the PAR-2/IL-33 axis is promoted by P. gingivalis infection in human gingival epithelial cells through a gingipain-dependent mechanism.

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