Bacterial DNA promotes proliferation of rat pancreatic stellate cells thorough toll-like receptor 9

Potential mechanisms for bacterially induced fibrosis

Taichi Nakamura, Tetsuhide Ito, takamasa ono, Hisato Igarashi, Nao Fujimori, Masahiko Uchida, Yusuke Niina, Mikihiko Yasuda, Koichi Suzuki, Ryoichi Takayanagi

研究成果: ジャーナルへの寄稿記事

11 引用 (Scopus)

抄録

Objectives: We hoped to clarify the possible role of CpG DNA as a trigger factor for overt pancreatic inflammation of pancreatic stellate cells (PSCs). Methods: Pancreatic stellate cells were isolated from the male Lewis rat. The expression of Toll-like receptor 9 (TLR9) messenger RNA and protein were evaluated by reverse transcription-polymerase chain reaction and immunofluorescent cytochemistry. Internalization of CpG DNA was analyzed by confocal laser scanning microscopy. Pancreatic stellate cells were incubated with CpG DNA, and then cell proliferation and migration were assessed. Results: Constitutive expression of TLR9 occurs at the messenger RNA and protein levels. After several minutes of CpG DNA administration, CpG DNA was observed on the cell membrane surface and in the cytoplasm and found to be translocating into the perinucleus of PSCs. Pancreatic stellate cells migrated and proliferated in dose- and time-dependent manners in response to simulation by CpG DNA. Proliferation of PSCs was observed 3 hours after administration (earlier than platelet-derived growth factor-induced proliferation), suggesting that PSCs respond readily to provide innate immunity. Endosomal acidification inhibitors attenuated CpG DNA-induced signaling, leading to suppression of DNA synthesis by PSCs. Conclusions: Our findings demonstrate that bacterial DNA promotes migration and proliferation of PSCs and suggest that bacterial DNA can initiate and sustain pancreatic inflammation and fibrosis by means of TLR9.

元の言語英語
ページ(範囲)823-831
ページ数9
ジャーナルPancreas
40
発行部数6
DOI
出版物ステータス出版済み - 8 1 2011

Fingerprint

Pancreatic Stellate Cells
Toll-Like Receptor 9
Bacterial DNA
Fibrosis
DNA
Inflammation
Histocytochemistry
Messenger RNA
Platelet-Derived Growth Factor
Innate Immunity
Confocal Microscopy
Reverse Transcription
Cell Movement
Cytoplasm
Proteins
Cell Proliferation
Cell Membrane

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

これを引用

Bacterial DNA promotes proliferation of rat pancreatic stellate cells thorough toll-like receptor 9 : Potential mechanisms for bacterially induced fibrosis. / Nakamura, Taichi; Ito, Tetsuhide; ono, takamasa; Igarashi, Hisato; Fujimori, Nao; Uchida, Masahiko; Niina, Yusuke; Yasuda, Mikihiko; Suzuki, Koichi; Takayanagi, Ryoichi.

:: Pancreas, 巻 40, 番号 6, 01.08.2011, p. 823-831.

研究成果: ジャーナルへの寄稿記事

Nakamura, Taichi ; Ito, Tetsuhide ; ono, takamasa ; Igarashi, Hisato ; Fujimori, Nao ; Uchida, Masahiko ; Niina, Yusuke ; Yasuda, Mikihiko ; Suzuki, Koichi ; Takayanagi, Ryoichi. / Bacterial DNA promotes proliferation of rat pancreatic stellate cells thorough toll-like receptor 9 : Potential mechanisms for bacterially induced fibrosis. :: Pancreas. 2011 ; 巻 40, 番号 6. pp. 823-831.
@article{8dddd304769f4f25b0ad8ad30add1869,
title = "Bacterial DNA promotes proliferation of rat pancreatic stellate cells thorough toll-like receptor 9: Potential mechanisms for bacterially induced fibrosis",
abstract = "Objectives: We hoped to clarify the possible role of CpG DNA as a trigger factor for overt pancreatic inflammation of pancreatic stellate cells (PSCs). Methods: Pancreatic stellate cells were isolated from the male Lewis rat. The expression of Toll-like receptor 9 (TLR9) messenger RNA and protein were evaluated by reverse transcription-polymerase chain reaction and immunofluorescent cytochemistry. Internalization of CpG DNA was analyzed by confocal laser scanning microscopy. Pancreatic stellate cells were incubated with CpG DNA, and then cell proliferation and migration were assessed. Results: Constitutive expression of TLR9 occurs at the messenger RNA and protein levels. After several minutes of CpG DNA administration, CpG DNA was observed on the cell membrane surface and in the cytoplasm and found to be translocating into the perinucleus of PSCs. Pancreatic stellate cells migrated and proliferated in dose- and time-dependent manners in response to simulation by CpG DNA. Proliferation of PSCs was observed 3 hours after administration (earlier than platelet-derived growth factor-induced proliferation), suggesting that PSCs respond readily to provide innate immunity. Endosomal acidification inhibitors attenuated CpG DNA-induced signaling, leading to suppression of DNA synthesis by PSCs. Conclusions: Our findings demonstrate that bacterial DNA promotes migration and proliferation of PSCs and suggest that bacterial DNA can initiate and sustain pancreatic inflammation and fibrosis by means of TLR9.",
author = "Taichi Nakamura and Tetsuhide Ito and takamasa ono and Hisato Igarashi and Nao Fujimori and Masahiko Uchida and Yusuke Niina and Mikihiko Yasuda and Koichi Suzuki and Ryoichi Takayanagi",
year = "2011",
month = "8",
day = "1",
doi = "10.1097/MPA.0b013e318224a501",
language = "English",
volume = "40",
pages = "823--831",
journal = "Pancreas",
issn = "0885-3177",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Bacterial DNA promotes proliferation of rat pancreatic stellate cells thorough toll-like receptor 9

T2 - Potential mechanisms for bacterially induced fibrosis

AU - Nakamura, Taichi

AU - Ito, Tetsuhide

AU - ono, takamasa

AU - Igarashi, Hisato

AU - Fujimori, Nao

AU - Uchida, Masahiko

AU - Niina, Yusuke

AU - Yasuda, Mikihiko

AU - Suzuki, Koichi

AU - Takayanagi, Ryoichi

PY - 2011/8/1

Y1 - 2011/8/1

N2 - Objectives: We hoped to clarify the possible role of CpG DNA as a trigger factor for overt pancreatic inflammation of pancreatic stellate cells (PSCs). Methods: Pancreatic stellate cells were isolated from the male Lewis rat. The expression of Toll-like receptor 9 (TLR9) messenger RNA and protein were evaluated by reverse transcription-polymerase chain reaction and immunofluorescent cytochemistry. Internalization of CpG DNA was analyzed by confocal laser scanning microscopy. Pancreatic stellate cells were incubated with CpG DNA, and then cell proliferation and migration were assessed. Results: Constitutive expression of TLR9 occurs at the messenger RNA and protein levels. After several minutes of CpG DNA administration, CpG DNA was observed on the cell membrane surface and in the cytoplasm and found to be translocating into the perinucleus of PSCs. Pancreatic stellate cells migrated and proliferated in dose- and time-dependent manners in response to simulation by CpG DNA. Proliferation of PSCs was observed 3 hours after administration (earlier than platelet-derived growth factor-induced proliferation), suggesting that PSCs respond readily to provide innate immunity. Endosomal acidification inhibitors attenuated CpG DNA-induced signaling, leading to suppression of DNA synthesis by PSCs. Conclusions: Our findings demonstrate that bacterial DNA promotes migration and proliferation of PSCs and suggest that bacterial DNA can initiate and sustain pancreatic inflammation and fibrosis by means of TLR9.

AB - Objectives: We hoped to clarify the possible role of CpG DNA as a trigger factor for overt pancreatic inflammation of pancreatic stellate cells (PSCs). Methods: Pancreatic stellate cells were isolated from the male Lewis rat. The expression of Toll-like receptor 9 (TLR9) messenger RNA and protein were evaluated by reverse transcription-polymerase chain reaction and immunofluorescent cytochemistry. Internalization of CpG DNA was analyzed by confocal laser scanning microscopy. Pancreatic stellate cells were incubated with CpG DNA, and then cell proliferation and migration were assessed. Results: Constitutive expression of TLR9 occurs at the messenger RNA and protein levels. After several minutes of CpG DNA administration, CpG DNA was observed on the cell membrane surface and in the cytoplasm and found to be translocating into the perinucleus of PSCs. Pancreatic stellate cells migrated and proliferated in dose- and time-dependent manners in response to simulation by CpG DNA. Proliferation of PSCs was observed 3 hours after administration (earlier than platelet-derived growth factor-induced proliferation), suggesting that PSCs respond readily to provide innate immunity. Endosomal acidification inhibitors attenuated CpG DNA-induced signaling, leading to suppression of DNA synthesis by PSCs. Conclusions: Our findings demonstrate that bacterial DNA promotes migration and proliferation of PSCs and suggest that bacterial DNA can initiate and sustain pancreatic inflammation and fibrosis by means of TLR9.

UR - http://www.scopus.com/inward/record.url?scp=80051548426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051548426&partnerID=8YFLogxK

U2 - 10.1097/MPA.0b013e318224a501

DO - 10.1097/MPA.0b013e318224a501

M3 - Article

VL - 40

SP - 823

EP - 831

JO - Pancreas

JF - Pancreas

SN - 0885-3177

IS - 6

ER -