Induction of hepatic stellate cell proliferation by LPS-stimulated peripheral blood mononuclear cells from patients with liver cirrhosis

Kyoko Toda, Naoki Kumagai, Kanji Tsuchimoto, Hiroyuki Inagaki, Tatsuo Suzuki, Tazuko Oishi, Kazuhiro Atsukawa, Hidetsugu Saito, Toshio Morizane, Toshifumi Hibi, Hiromasa Ishii

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

We studied hepatic stellate cell proliferation in vitro. Peripheral blood mononuclear cells (PBMC) from patients with chronic active hepatitis C (CAH) and liver cirrhosis (LC) were cultured for 24 h in the presence or absence of Escherichia coli lipopolysaccharides (LPS). Hepatic stellate cell proliferation induced by the culture supernatants was measured, and interleukin-1 (IL-1) and IL-6 levels in the culture supernatants were quantified. Culture supernatants of LPS-stimulated PBMC from LC patients induced rat hepatic stellate cell proliferation by almost 2.8-fold (stimulation index, 2.83 ± 1.41) compared with when the cells were cultured without addition of PBMC culture supernatants. Production of IL-1β was significantly higher in the culture supernatants of both CAH and LC patients than in those of ten healthy controls (P < 0.01 and P < 0.05, respectively). But there was no significant correlation between IL-1 production and the induction of hepatic stellate cell proliferation by the culture supernatants. Although there were no significant differences in IL-6 production by LPS-stimulated PBMC among healthy controls and CAH and LC patients, we observed a significant correlation between IL-6 production and the induction of hepatic stellate cell proliferation in the culture supernatants of LC patients. Rat hepatic stellate cells themselves produced IL-6, and treatment with IL-6 antisense oligodeoxynucleotides suppressed the cell proliferation, suggesting that IL-6 is an autocrine growth factor for hepatic stellate cells. The addition of human recombinant IL-6 (hrIL-6) augmented rat hepatic stellate cell proliferation, indicating that excessive IL-6 may further facilitate cell proliferation. These findings suggest that a cytokine cascade including IL-6 may participate in hepatic stellate cell proliferation in LC patients when they are exposed to endotoxin.

Original languageEnglish
Pages (from-to)214-220
Number of pages7
JournalJournal of Gastroenterology
Volume35
Issue number3
Publication statusPublished - 2000 Mar

Fingerprint

Hepatic Stellate Cells
Liver Cirrhosis
Lipopolysaccharides
Interleukin-6
Blood Cells
Cell Proliferation
Chronic Hepatitis C
Chronic Hepatitis
Interleukin-1
Cell Culture Techniques
Oligodeoxyribonucleotides
Endotoxins
Cultured Cells
Intercellular Signaling Peptides and Proteins
Cytokines
Escherichia coli

Keywords

  • Culture supernatant
  • Hepatic stellate cell
  • Interleukin-6
  • Liver cirrhosis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Toda, K., Kumagai, N., Tsuchimoto, K., Inagaki, H., Suzuki, T., Oishi, T., ... Ishii, H. (2000). Induction of hepatic stellate cell proliferation by LPS-stimulated peripheral blood mononuclear cells from patients with liver cirrhosis. Journal of Gastroenterology, 35(3), 214-220.

Induction of hepatic stellate cell proliferation by LPS-stimulated peripheral blood mononuclear cells from patients with liver cirrhosis. / Toda, Kyoko; Kumagai, Naoki; Tsuchimoto, Kanji; Inagaki, Hiroyuki; Suzuki, Tatsuo; Oishi, Tazuko; Atsukawa, Kazuhiro; Saito, Hidetsugu; Morizane, Toshio; Hibi, Toshifumi; Ishii, Hiromasa.

In: Journal of Gastroenterology, Vol. 35, No. 3, 03.2000, p. 214-220.

Research output: Contribution to journalArticle

Toda, K, Kumagai, N, Tsuchimoto, K, Inagaki, H, Suzuki, T, Oishi, T, Atsukawa, K, Saito, H, Morizane, T, Hibi, T & Ishii, H 2000, 'Induction of hepatic stellate cell proliferation by LPS-stimulated peripheral blood mononuclear cells from patients with liver cirrhosis', Journal of Gastroenterology, vol. 35, no. 3, pp. 214-220.
Toda, Kyoko ; Kumagai, Naoki ; Tsuchimoto, Kanji ; Inagaki, Hiroyuki ; Suzuki, Tatsuo ; Oishi, Tazuko ; Atsukawa, Kazuhiro ; Saito, Hidetsugu ; Morizane, Toshio ; Hibi, Toshifumi ; Ishii, Hiromasa. / Induction of hepatic stellate cell proliferation by LPS-stimulated peripheral blood mononuclear cells from patients with liver cirrhosis. In: Journal of Gastroenterology. 2000 ; Vol. 35, No. 3. pp. 214-220.
@article{38ebccc106814277898fb73e8b3308d6,
title = "Induction of hepatic stellate cell proliferation by LPS-stimulated peripheral blood mononuclear cells from patients with liver cirrhosis",
abstract = "We studied hepatic stellate cell proliferation in vitro. Peripheral blood mononuclear cells (PBMC) from patients with chronic active hepatitis C (CAH) and liver cirrhosis (LC) were cultured for 24 h in the presence or absence of Escherichia coli lipopolysaccharides (LPS). Hepatic stellate cell proliferation induced by the culture supernatants was measured, and interleukin-1 (IL-1) and IL-6 levels in the culture supernatants were quantified. Culture supernatants of LPS-stimulated PBMC from LC patients induced rat hepatic stellate cell proliferation by almost 2.8-fold (stimulation index, 2.83 ± 1.41) compared with when the cells were cultured without addition of PBMC culture supernatants. Production of IL-1β was significantly higher in the culture supernatants of both CAH and LC patients than in those of ten healthy controls (P < 0.01 and P < 0.05, respectively). But there was no significant correlation between IL-1 production and the induction of hepatic stellate cell proliferation by the culture supernatants. Although there were no significant differences in IL-6 production by LPS-stimulated PBMC among healthy controls and CAH and LC patients, we observed a significant correlation between IL-6 production and the induction of hepatic stellate cell proliferation in the culture supernatants of LC patients. Rat hepatic stellate cells themselves produced IL-6, and treatment with IL-6 antisense oligodeoxynucleotides suppressed the cell proliferation, suggesting that IL-6 is an autocrine growth factor for hepatic stellate cells. The addition of human recombinant IL-6 (hrIL-6) augmented rat hepatic stellate cell proliferation, indicating that excessive IL-6 may further facilitate cell proliferation. These findings suggest that a cytokine cascade including IL-6 may participate in hepatic stellate cell proliferation in LC patients when they are exposed to endotoxin.",
keywords = "Culture supernatant, Hepatic stellate cell, Interleukin-6, Liver cirrhosis",
author = "Kyoko Toda and Naoki Kumagai and Kanji Tsuchimoto and Hiroyuki Inagaki and Tatsuo Suzuki and Tazuko Oishi and Kazuhiro Atsukawa and Hidetsugu Saito and Toshio Morizane and Toshifumi Hibi and Hiromasa Ishii",
year = "2000",
month = "3",
language = "English",
volume = "35",
pages = "214--220",
journal = "Journal of Gastroenterology",
issn = "0944-1174",
publisher = "Springer Japan",
number = "3",

}

TY - JOUR

T1 - Induction of hepatic stellate cell proliferation by LPS-stimulated peripheral blood mononuclear cells from patients with liver cirrhosis

AU - Toda, Kyoko

AU - Kumagai, Naoki

AU - Tsuchimoto, Kanji

AU - Inagaki, Hiroyuki

AU - Suzuki, Tatsuo

AU - Oishi, Tazuko

AU - Atsukawa, Kazuhiro

AU - Saito, Hidetsugu

AU - Morizane, Toshio

AU - Hibi, Toshifumi

AU - Ishii, Hiromasa

PY - 2000/3

Y1 - 2000/3

N2 - We studied hepatic stellate cell proliferation in vitro. Peripheral blood mononuclear cells (PBMC) from patients with chronic active hepatitis C (CAH) and liver cirrhosis (LC) were cultured for 24 h in the presence or absence of Escherichia coli lipopolysaccharides (LPS). Hepatic stellate cell proliferation induced by the culture supernatants was measured, and interleukin-1 (IL-1) and IL-6 levels in the culture supernatants were quantified. Culture supernatants of LPS-stimulated PBMC from LC patients induced rat hepatic stellate cell proliferation by almost 2.8-fold (stimulation index, 2.83 ± 1.41) compared with when the cells were cultured without addition of PBMC culture supernatants. Production of IL-1β was significantly higher in the culture supernatants of both CAH and LC patients than in those of ten healthy controls (P < 0.01 and P < 0.05, respectively). But there was no significant correlation between IL-1 production and the induction of hepatic stellate cell proliferation by the culture supernatants. Although there were no significant differences in IL-6 production by LPS-stimulated PBMC among healthy controls and CAH and LC patients, we observed a significant correlation between IL-6 production and the induction of hepatic stellate cell proliferation in the culture supernatants of LC patients. Rat hepatic stellate cells themselves produced IL-6, and treatment with IL-6 antisense oligodeoxynucleotides suppressed the cell proliferation, suggesting that IL-6 is an autocrine growth factor for hepatic stellate cells. The addition of human recombinant IL-6 (hrIL-6) augmented rat hepatic stellate cell proliferation, indicating that excessive IL-6 may further facilitate cell proliferation. These findings suggest that a cytokine cascade including IL-6 may participate in hepatic stellate cell proliferation in LC patients when they are exposed to endotoxin.

AB - We studied hepatic stellate cell proliferation in vitro. Peripheral blood mononuclear cells (PBMC) from patients with chronic active hepatitis C (CAH) and liver cirrhosis (LC) were cultured for 24 h in the presence or absence of Escherichia coli lipopolysaccharides (LPS). Hepatic stellate cell proliferation induced by the culture supernatants was measured, and interleukin-1 (IL-1) and IL-6 levels in the culture supernatants were quantified. Culture supernatants of LPS-stimulated PBMC from LC patients induced rat hepatic stellate cell proliferation by almost 2.8-fold (stimulation index, 2.83 ± 1.41) compared with when the cells were cultured without addition of PBMC culture supernatants. Production of IL-1β was significantly higher in the culture supernatants of both CAH and LC patients than in those of ten healthy controls (P < 0.01 and P < 0.05, respectively). But there was no significant correlation between IL-1 production and the induction of hepatic stellate cell proliferation by the culture supernatants. Although there were no significant differences in IL-6 production by LPS-stimulated PBMC among healthy controls and CAH and LC patients, we observed a significant correlation between IL-6 production and the induction of hepatic stellate cell proliferation in the culture supernatants of LC patients. Rat hepatic stellate cells themselves produced IL-6, and treatment with IL-6 antisense oligodeoxynucleotides suppressed the cell proliferation, suggesting that IL-6 is an autocrine growth factor for hepatic stellate cells. The addition of human recombinant IL-6 (hrIL-6) augmented rat hepatic stellate cell proliferation, indicating that excessive IL-6 may further facilitate cell proliferation. These findings suggest that a cytokine cascade including IL-6 may participate in hepatic stellate cell proliferation in LC patients when they are exposed to endotoxin.

KW - Culture supernatant

KW - Hepatic stellate cell

KW - Interleukin-6

KW - Liver cirrhosis

UR - http://www.scopus.com/inward/record.url?scp=0034034594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034034594&partnerID=8YFLogxK

M3 - Article

C2 - 10755691

AN - SCOPUS:0034034594

VL - 35

SP - 214

EP - 220

JO - Journal of Gastroenterology

JF - Journal of Gastroenterology

SN - 0944-1174

IS - 3

ER -