RRC ID 52394
Author Ohno T, Yamamoto G, Hayashi JI, Nishida E, Goto H, Sasaki Y, Kikuchi T, Fukuda M, Hasegawa Y, Mogi M, Mitani A.
Title Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells.
Journal PLoS One
Abstract 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 1β (IL-1β), IL-8, and tumor necrosis factor-α (TNF-α) mRNA and protein levels in Ca9-22 cells. Small-interfering (si)RNA-mediated ANGPTL2 knockdown in Ca9-22 cells reduced IL-1β, IL-8 and TNF-α mRNA and protein levels compared with control siRNA (p<0.01) in P. gingivalis LPS-stimulated Ca9-22 cells. Antibodies against integrin α5β1, 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 α5β1 → 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.
Volume 12(9)
Pages e0184825
Published 2017-9-21
DOI 10.1371/journal.pone.0184825
PII PONE-D-17-16215
PMID 28934245
PMC PMC5608282
MeSH Angiopoietin-like Proteins Angiopoietins / administration & dosage Angiopoietins / antagonists & inhibitors Angiopoietins / genetics Angiopoietins / metabolism* Cell Line Cytokines / metabolism Epithelial Cells / immunology Epithelial Cells / microbiology Gingiva / immunology* Gingiva / microbiology Humans Integrin alpha5beta1 / antagonists & inhibitors Integrin alpha5beta1 / metabolism Lipopolysaccharides / metabolism* Periodontitis / immunology* Periodontitis / microbiology Porphyromonas gingivalis / metabolism* RNA, Messenger / metabolism Recombinant Proteins / administration & dosage Recombinant Proteins / metabolism Toll-Like Receptor 2 / antagonists & inhibitors Toll-Like Receptor 2 / genetics Toll-Like Receptor 2 / metabolism Toll-Like Receptor 4 / antagonists & inhibitors Toll-Like Receptor 4 / genetics Toll-Like Receptor 4 / metabolism
IF 2.74
Times Cited 10
Human and Animal Cells Ca9-22(RCB1976)