title: Porphyromonas gingivalis Gingipain-Dependently Enhances IL-33 Production in Human Gingival Epithelial Cells.
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.
authors.affiliation: Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.|Division of Oral Microbiology, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tada
authors.affiliation: Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka, Kagoshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuyama
authors.affiliation: Division of Oral Diagnosis, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishioka
authors.affiliation: Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hagiwara
authors.affiliation: Department of Oral Medical Science, Ohu University School of Dentistry, Koriyama, Fukushima, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kiyoura
authors.affiliation: Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Shimauchi
authors.affiliation: Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsushita
mesh_terms: D018829:Adhesins, Bacterial / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D000080867:Gingipain Cysteine Endopeptidases; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D000067596:Interleukin-33 / Q000235:genetics / Q000378:metabolism*; D010518:Periodontitis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018829:Adhesins, Bacterial; D016207:Cytokines; D000080867:Gingipain Cysteine Endopeptidases; D000067596:Interleukin-33; D012333:RNA, Messenger; D003546:Cysteine Endopeptidases