Toll-like receptor 4 signaling has a critical role in Porphyromonas gingivalis-accelerated neointimal formation after arterial injury in mice

Naho Kobayashi, Jun Ichi Suzuki, Norio Aoyama, Hiroki Sato, Shouta Akimoto, Kouji Wakayama, Hidetoshi Kumagai, Yuichi Ikeda, Hiroshi Akazawa, Issei Komuro, Yuichi Izumi, Mitsuaki Isobe

Research output: Contribution to journalArticle

Abstract

Recently, we reported that a periodontopathic pathogen, Porphyromonas gingivalis (P. gingivalis), infection induced neointimal hyperplasia with enhanced expression of monocyte chemoattractant protein (MCP)-1 after arterial injury in wild-type mice. Toll-like receptor (TLR) 4 is known to be a key receptor for virulence factors of P. gingivalis. The aim of this study is to assess the hypothesis that TLR4 has a critical role in periodontopathic bacteria-induced neointimal formation after an arterial injury. Wild-type and TLR4-deficient mice were used in this study. The femoral arteries were injured, and P. gingivalis or vehicle was injected subcutaneously once per week. Fourteen days after arterial injury, murine femoral arteries were obtained for histopathological and immunohistochemical analyses. The anti-P. gingivalis IgG levels in P. gingivalis-infected groups were significantly increased compared with the anti-P. gingivalis IgG levels of the corresponding non-infected groups in both wild-type and TLR4-deficient mice. TLR4 deficiency negated P. gingivalis-induced neointimal formation compared with that observed in wild-type mice and reduced the number of MCP-1 positive cells in the neointimal area. We conclude that P. gingivalis infection may promote neointimal formation after an arterial injury through TLR4 signaling.

Original languageEnglish (US)
Pages (from-to)717-722
Number of pages6
JournalHypertension Research
Volume39
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

Porphyromonas gingivalis
Toll-Like Receptor 4
Wounds and Injuries
Chemokine CCL2
Femoral Artery
Immunoglobulin G
Virulence Factors
Infection
Hyperplasia
Bacteria

Keywords

  • arterial injury
  • periodontal disease
  • Porphyromonas gingivalis
  • toll-like receptor

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Toll-like receptor 4 signaling has a critical role in Porphyromonas gingivalis-accelerated neointimal formation after arterial injury in mice. / Kobayashi, Naho; Suzuki, Jun Ichi; Aoyama, Norio; Sato, Hiroki; Akimoto, Shouta; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Komuro, Issei; Izumi, Yuichi; Isobe, Mitsuaki.

In: Hypertension Research, Vol. 39, No. 10, 01.10.2016, p. 717-722.

Research output: Contribution to journalArticle

Kobayashi, N, Suzuki, JI, Aoyama, N, Sato, H, Akimoto, S, Wakayama, K, Kumagai, H, Ikeda, Y, Akazawa, H, Komuro, I, Izumi, Y & Isobe, M 2016, 'Toll-like receptor 4 signaling has a critical role in Porphyromonas gingivalis-accelerated neointimal formation after arterial injury in mice', Hypertension Research, vol. 39, no. 10, pp. 717-722. https://doi.org/10.1038/hr.2016.58
Kobayashi, Naho ; Suzuki, Jun Ichi ; Aoyama, Norio ; Sato, Hiroki ; Akimoto, Shouta ; Wakayama, Kouji ; Kumagai, Hidetoshi ; Ikeda, Yuichi ; Akazawa, Hiroshi ; Komuro, Issei ; Izumi, Yuichi ; Isobe, Mitsuaki. / Toll-like receptor 4 signaling has a critical role in Porphyromonas gingivalis-accelerated neointimal formation after arterial injury in mice. In: Hypertension Research. 2016 ; Vol. 39, No. 10. pp. 717-722.
@article{c2668c43df9145a7a93ecb46034da588,
title = "Toll-like receptor 4 signaling has a critical role in Porphyromonas gingivalis-accelerated neointimal formation after arterial injury in mice",
abstract = "Recently, we reported that a periodontopathic pathogen, Porphyromonas gingivalis (P. gingivalis), infection induced neointimal hyperplasia with enhanced expression of monocyte chemoattractant protein (MCP)-1 after arterial injury in wild-type mice. Toll-like receptor (TLR) 4 is known to be a key receptor for virulence factors of P. gingivalis. The aim of this study is to assess the hypothesis that TLR4 has a critical role in periodontopathic bacteria-induced neointimal formation after an arterial injury. Wild-type and TLR4-deficient mice were used in this study. The femoral arteries were injured, and P. gingivalis or vehicle was injected subcutaneously once per week. Fourteen days after arterial injury, murine femoral arteries were obtained for histopathological and immunohistochemical analyses. The anti-P. gingivalis IgG levels in P. gingivalis-infected groups were significantly increased compared with the anti-P. gingivalis IgG levels of the corresponding non-infected groups in both wild-type and TLR4-deficient mice. TLR4 deficiency negated P. gingivalis-induced neointimal formation compared with that observed in wild-type mice and reduced the number of MCP-1 positive cells in the neointimal area. We conclude that P. gingivalis infection may promote neointimal formation after an arterial injury through TLR4 signaling.",
keywords = "arterial injury, periodontal disease, Porphyromonas gingivalis, toll-like receptor",
author = "Naho Kobayashi and Suzuki, {Jun Ichi} and Norio Aoyama and Hiroki Sato and Shouta Akimoto and Kouji Wakayama and Hidetoshi Kumagai and Yuichi Ikeda and Hiroshi Akazawa and Issei Komuro and Yuichi Izumi and Mitsuaki Isobe",
year = "2016",
month = "10",
day = "1",
doi = "10.1038/hr.2016.58",
language = "English (US)",
volume = "39",
pages = "717--722",
journal = "Hypertension Research",
issn = "0916-9636",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Toll-like receptor 4 signaling has a critical role in Porphyromonas gingivalis-accelerated neointimal formation after arterial injury in mice

AU - Kobayashi, Naho

AU - Suzuki, Jun Ichi

AU - Aoyama, Norio

AU - Sato, Hiroki

AU - Akimoto, Shouta

AU - Wakayama, Kouji

AU - Kumagai, Hidetoshi

AU - Ikeda, Yuichi

AU - Akazawa, Hiroshi

AU - Komuro, Issei

AU - Izumi, Yuichi

AU - Isobe, Mitsuaki

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Recently, we reported that a periodontopathic pathogen, Porphyromonas gingivalis (P. gingivalis), infection induced neointimal hyperplasia with enhanced expression of monocyte chemoattractant protein (MCP)-1 after arterial injury in wild-type mice. Toll-like receptor (TLR) 4 is known to be a key receptor for virulence factors of P. gingivalis. The aim of this study is to assess the hypothesis that TLR4 has a critical role in periodontopathic bacteria-induced neointimal formation after an arterial injury. Wild-type and TLR4-deficient mice were used in this study. The femoral arteries were injured, and P. gingivalis or vehicle was injected subcutaneously once per week. Fourteen days after arterial injury, murine femoral arteries were obtained for histopathological and immunohistochemical analyses. The anti-P. gingivalis IgG levels in P. gingivalis-infected groups were significantly increased compared with the anti-P. gingivalis IgG levels of the corresponding non-infected groups in both wild-type and TLR4-deficient mice. TLR4 deficiency negated P. gingivalis-induced neointimal formation compared with that observed in wild-type mice and reduced the number of MCP-1 positive cells in the neointimal area. We conclude that P. gingivalis infection may promote neointimal formation after an arterial injury through TLR4 signaling.

AB - Recently, we reported that a periodontopathic pathogen, Porphyromonas gingivalis (P. gingivalis), infection induced neointimal hyperplasia with enhanced expression of monocyte chemoattractant protein (MCP)-1 after arterial injury in wild-type mice. Toll-like receptor (TLR) 4 is known to be a key receptor for virulence factors of P. gingivalis. The aim of this study is to assess the hypothesis that TLR4 has a critical role in periodontopathic bacteria-induced neointimal formation after an arterial injury. Wild-type and TLR4-deficient mice were used in this study. The femoral arteries were injured, and P. gingivalis or vehicle was injected subcutaneously once per week. Fourteen days after arterial injury, murine femoral arteries were obtained for histopathological and immunohistochemical analyses. The anti-P. gingivalis IgG levels in P. gingivalis-infected groups were significantly increased compared with the anti-P. gingivalis IgG levels of the corresponding non-infected groups in both wild-type and TLR4-deficient mice. TLR4 deficiency negated P. gingivalis-induced neointimal formation compared with that observed in wild-type mice and reduced the number of MCP-1 positive cells in the neointimal area. We conclude that P. gingivalis infection may promote neointimal formation after an arterial injury through TLR4 signaling.

KW - arterial injury

KW - periodontal disease

KW - Porphyromonas gingivalis

KW - toll-like receptor

UR - http://www.scopus.com/inward/record.url?scp=84989926439&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84989926439&partnerID=8YFLogxK

U2 - 10.1038/hr.2016.58

DO - 10.1038/hr.2016.58

M3 - Article

VL - 39

SP - 717

EP - 722

JO - Hypertension Research

JF - Hypertension Research

SN - 0916-9636

IS - 10

ER -