Porphyromonas gingivalis gingipain-dependently enhances IL-33 production in human gingival epithelial cells

Hiroyuki Tada, Takashi Matsuyama, Takashi Nishioka, Makoto Hagiwara, Yusuke Kiyoura, Hidetoshi Shimauchi, Kenji Matsushita

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


The cytokine IL-33 is constitutively expressed in epithelial cells and it augments Th2 cytokinemediated 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-êB 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.

Original languageEnglish
Article numbere0152794
JournalPloS one
Issue number4
Publication statusPublished - 2016 Apr

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General


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