Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells

被引：28

作者：

Ohno, Tasuku ^{[1
]}

Yamamoto, Genta ^{[1
]}

Hayashi, Jun-ichiro ^{[1
]}

Nishida, Eisaku ^{[1
]}

Goto, Hisashi ^{[1
]}

Sasaki, Yasuyuki ^{[1
]}

Kikuchi, Takeshi ^{[1
]}

Fukuda, Mitsuo ^{[1
]}

Hasegawa, Yoshiaki ^{[2
]}

Mogi, Makio ^{[3
]}

Mitani, Akio ^{[1
]}

机构：

[1] Aichi Gakuin Univ, Dept Periodontol, Sch Dent, Chikusa Ku, Nagoya, Aichi, Japan

[2] Aichi Gakuin Univ, Dept Microbiol, Sch Dent, Chikusa Ku, Nagoya, Aichi, Japan

[3] Aichi Gakuin Univ, Dept Integrat Educ Pharm, Sch Pharm, Chikusa Ku, Nagoya, Aichi, Japan

来源：

PLOS ONE | 2017年 / 12卷 / 09期

关键词：

TUMOR-NECROSIS-FACTOR; TOLL-LIKE RECEPTORS; PERIODONTAL-DISEASE; CREVICULAR FLUID; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; FACTOR-ALPHA; EXPRESSION; ASSOCIATION; ANGPTL2; RISK;

D O I：

10.1371/journal.pone.0184825

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Angiopoietin-like protein 2 (ANGPTL2) maintains tissue homeostasis by inducing inflammation and angiogenesis. It is produced in infiltrating immune cells or resident cells, such as adipocytes, vascular endothelial cells, and tumor cells. We hypothesized that ANGPTL2 might play an important role as a unique mediator in both systemic and periodontal disease. We demonstrated an increased ANGPTL2 concentration in gingival crevicular fluid from chronic periodontitis patients. Porphyromonas gingivalis lipopolysaccharide (LPS) treatment strongly induced ANGPTL2 mRNA and protein levels in Ca9-22 human gingival epithelial cells. Recombinant human ANGPTL2 increased interleukin 1 beta (IL-1 beta), IL-8, and tumor necrosis factor-a (TNF-alpha) mRNA and protein levels in Ca9-22 cells. Small-interfering (si) RNA-mediated ANGPTL2 knockdown in Ca9-22 cells reduced IL-1 beta, IL-8 and TNF-a mRNA and protein levels compared with control siRNA (p<0.01) in P. gingivalis LPS-stimulated Ca9-22 cells. Antibodies against integrin alpha 5 beta 1, an ANGPTL receptor, blocked induction of these inflammatory cytokines in P. gingivalis LPS-treated Ca9-22 cells, suggesting that secreted ANGPTL induces inflammatory cytokines in gingival epithelial cells via an autocrine loop. The classic sequential cascade of P. gingivalis LPS! inflammatory cytokine induction is well established. However, in the current study, we reveal a novel cascade comprising sequential P. gingivalis LPS! ANGPTL2! integrin alpha 5 beta inflammatory cytokine induction, which might be responsible for inducing potent periodontal disorganization activity in gingival epithelial cells. Via this pathway, ANGPTL2 functions in the pathogenesis of periodontitis and contributes to prolonging chronic inflammation in patients with systemic disease.

引用

页数：14

共 41 条

[1] Association between extent of periodontal attachment loss and self-reported history of heart attack: An analysis of NHANES III data [J].