Modulation of Wnt5a Expression by Periodontopathic Bacteria

Wingless proteins, termed Wnt, are involved in embryonic development, blood cell differentiation, and tumorigenesis. In mammalian hematopoiesis, Wnt signaling is essential for stem-cell homeostasis and lymphocyte differentiation. Recent studies have suggested that these molecules are associated with...

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Main Authors: Nanbara, Hiromi, Wara-aswapati, Nawarat, Nagasawa, Toshiyuki, Yoshida, Yasuhiro, Yashiro, Reiko, Bando, Yukiko, Kobayashi, Hiroaki, Khongcharoensuk, Janjura, Hormdee, Doosadee, Pitiphat, Waranuch, Boch, Jason A., Izumi, Yuichi
Format: Online
Language:English
Published: Public Library of Science 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317782/
id pubmed-3317782
recordtype oai_dc
spelling pubmed-33177822012-04-06 Modulation of Wnt5a Expression by Periodontopathic Bacteria Nanbara, Hiromi Wara-aswapati, Nawarat Nagasawa, Toshiyuki Yoshida, Yasuhiro Yashiro, Reiko Bando, Yukiko Kobayashi, Hiroaki Khongcharoensuk, Janjura Hormdee, Doosadee Pitiphat, Waranuch Boch, Jason A. Izumi, Yuichi Research Article Wingless proteins, termed Wnt, are involved in embryonic development, blood cell differentiation, and tumorigenesis. In mammalian hematopoiesis, Wnt signaling is essential for stem-cell homeostasis and lymphocyte differentiation. Recent studies have suggested that these molecules are associated with cardiovascular diseases, rheumatoid arthritis, and osteoarthritis. Furthermore, Wnt5a signaling is essential for the general inflammatory response of human macrophages. Periodontitis is a chronic inflammatory disease caused by gram-negative periodontopathic bacteria and the resultant host immune response. Periodontitis is characterized by loss of tooth-supporting structures and alveolar bone resorption. There have been no previous reports on Wnt5a expression in periodontitis tissue, and only few study reported the molecular mechanisms of Wnt5a expression in LPS-stimulated monocytic cells. Using RT-PCR, we demonstrated that Wnt5a mRNA expression was up-regulated in chronic periodontitis tissue as compared to healthy control tissue. P. gingivalis LPS induced Wnt5a mRNA in the human monocytic cell line THP-1 with a peak at 4 hrs after stimulation. P. gingivalis LPS induced higher up-regulation of Wnt5a mRNA than E. coli LPS. The LPS receptors TLR2 and TLR4 were equally expressed on the surface of THP-1 cells. P. gingivalis LPS induced IκBα degradation and was able to increase the NF-κB binding activity to DNA. P. gingivalis LPS-induced Wnt5a expression was inhibited by NF-κB inhibitors, suggesting NF-κB involvement. Furthermore, IFN-γ synergistically enhanced the P. gingivalis LPS-induced production of Wnt5a. Pharmacological investigation and siRNA experiments showed that STAT1 was important for P. gingivalis LPS-induced Wnt5a expression. These results suggest that the modulation of Wnt5a expression by P. gingivalis may play an important role in the periodontal inflammatory process and serve a target for the development of new therapies. Public Library of Science 2012-04-02 /pmc/articles/PMC3317782/ /pubmed/22485170 http://dx.doi.org/10.1371/journal.pone.0034434 Text en Nanbara 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Nanbara, Hiromi
Wara-aswapati, Nawarat
Nagasawa, Toshiyuki
Yoshida, Yasuhiro
Yashiro, Reiko
Bando, Yukiko
Kobayashi, Hiroaki
Khongcharoensuk, Janjura
Hormdee, Doosadee
Pitiphat, Waranuch
Boch, Jason A.
Izumi, Yuichi
spellingShingle Nanbara, Hiromi
Wara-aswapati, Nawarat
Nagasawa, Toshiyuki
Yoshida, Yasuhiro
Yashiro, Reiko
Bando, Yukiko
Kobayashi, Hiroaki
Khongcharoensuk, Janjura
Hormdee, Doosadee
Pitiphat, Waranuch
Boch, Jason A.
Izumi, Yuichi
Modulation of Wnt5a Expression by Periodontopathic Bacteria
author_facet Nanbara, Hiromi
Wara-aswapati, Nawarat
Nagasawa, Toshiyuki
Yoshida, Yasuhiro
Yashiro, Reiko
Bando, Yukiko
Kobayashi, Hiroaki
Khongcharoensuk, Janjura
Hormdee, Doosadee
Pitiphat, Waranuch
Boch, Jason A.
Izumi, Yuichi
author_sort Nanbara, Hiromi
title Modulation of Wnt5a Expression by Periodontopathic Bacteria
title_short Modulation of Wnt5a Expression by Periodontopathic Bacteria
title_full Modulation of Wnt5a Expression by Periodontopathic Bacteria
title_fullStr Modulation of Wnt5a Expression by Periodontopathic Bacteria
title_full_unstemmed Modulation of Wnt5a Expression by Periodontopathic Bacteria
title_sort modulation of wnt5a expression by periodontopathic bacteria
description Wingless proteins, termed Wnt, are involved in embryonic development, blood cell differentiation, and tumorigenesis. In mammalian hematopoiesis, Wnt signaling is essential for stem-cell homeostasis and lymphocyte differentiation. Recent studies have suggested that these molecules are associated with cardiovascular diseases, rheumatoid arthritis, and osteoarthritis. Furthermore, Wnt5a signaling is essential for the general inflammatory response of human macrophages. Periodontitis is a chronic inflammatory disease caused by gram-negative periodontopathic bacteria and the resultant host immune response. Periodontitis is characterized by loss of tooth-supporting structures and alveolar bone resorption. There have been no previous reports on Wnt5a expression in periodontitis tissue, and only few study reported the molecular mechanisms of Wnt5a expression in LPS-stimulated monocytic cells. Using RT-PCR, we demonstrated that Wnt5a mRNA expression was up-regulated in chronic periodontitis tissue as compared to healthy control tissue. P. gingivalis LPS induced Wnt5a mRNA in the human monocytic cell line THP-1 with a peak at 4 hrs after stimulation. P. gingivalis LPS induced higher up-regulation of Wnt5a mRNA than E. coli LPS. The LPS receptors TLR2 and TLR4 were equally expressed on the surface of THP-1 cells. P. gingivalis LPS induced IκBα degradation and was able to increase the NF-κB binding activity to DNA. P. gingivalis LPS-induced Wnt5a expression was inhibited by NF-κB inhibitors, suggesting NF-κB involvement. Furthermore, IFN-γ synergistically enhanced the P. gingivalis LPS-induced production of Wnt5a. Pharmacological investigation and siRNA experiments showed that STAT1 was important for P. gingivalis LPS-induced Wnt5a expression. These results suggest that the modulation of Wnt5a expression by P. gingivalis may play an important role in the periodontal inflammatory process and serve a target for the development of new therapies.
publisher Public Library of Science
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317782/
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