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

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...

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Autores principales: Ohno, Tasuku, Yamamoto, Genta, Hayashi, Jun-ichiro, Nishida, Eisaku, Goto, Hisashi, Sasaki, Yasuyuki, Kikuchi, Takeshi, Fukuda, Mitsuo, Hasegawa, Yoshiaki, Mogi, Makio, Mitani, Akio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608282/
https://www.ncbi.nlm.nih.gov/pubmed/28934245
http://dx.doi.org/10.1371/journal.pone.0184825
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author Ohno, Tasuku
Yamamoto, Genta
Hayashi, Jun-ichiro
Nishida, Eisaku
Goto, Hisashi
Sasaki, Yasuyuki
Kikuchi, Takeshi
Fukuda, Mitsuo
Hasegawa, Yoshiaki
Mogi, Makio
Mitani, Akio
author_facet Ohno, Tasuku
Yamamoto, Genta
Hayashi, Jun-ichiro
Nishida, Eisaku
Goto, Hisashi
Sasaki, Yasuyuki
Kikuchi, Takeshi
Fukuda, Mitsuo
Hasegawa, Yoshiaki
Mogi, Makio
Mitani, Akio
author_sort Ohno, Tasuku
collection PubMed
description 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.
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spelling pubmed-56082822017-10-09 Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells Ohno, Tasuku Yamamoto, Genta Hayashi, Jun-ichiro Nishida, Eisaku Goto, Hisashi Sasaki, Yasuyuki Kikuchi, Takeshi Fukuda, Mitsuo Hasegawa, Yoshiaki Mogi, Makio Mitani, Akio PLoS One Research Article 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. Public Library of Science 2017-09-21 /pmc/articles/PMC5608282/ /pubmed/28934245 http://dx.doi.org/10.1371/journal.pone.0184825 Text en © 2017 Ohno et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ohno, Tasuku
Yamamoto, Genta
Hayashi, Jun-ichiro
Nishida, Eisaku
Goto, Hisashi
Sasaki, Yasuyuki
Kikuchi, Takeshi
Fukuda, Mitsuo
Hasegawa, Yoshiaki
Mogi, Makio
Mitani, Akio
Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells
title Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells
title_full Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells
title_fullStr Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells
title_full_unstemmed Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells
title_short Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells
title_sort angiopoietin-like protein 2 regulates porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608282/
https://www.ncbi.nlm.nih.gov/pubmed/28934245
http://dx.doi.org/10.1371/journal.pone.0184825
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