Research ExplorerPublicationsCCR1 and CCR5 promote hepatic fibrosis in mice.

CCR1 and CCR5 promote hepatic fibrosis in mice.

Standard

CCR1 and CCR5 promote hepatic fibrosis in mice. / Seki, Ekihiro; Samuele, De Minicis; Gwak, Geum-Youn; Kluwe, Johannes; Inokuchi, Sayaka; Bursill, Christina A; Llovet, Josep M; Brenner, David A; Schwabe, Robert F.

In: J CLIN INVEST, Vol. 119, No. 7, 7, 2009, p. 1858-1870.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Seki, E, Samuele, DM, Gwak, G-Y, Kluwe, J, Inokuchi, S, Bursill, CA, Llovet, JM, Brenner, DA & Schwabe, RF 2009, 'CCR1 and CCR5 promote hepatic fibrosis in mice.', J CLIN INVEST, vol. 119, no. 7, 7, pp. 1858-1870. <http://www.ncbi.nlm.nih.gov/pubmed/19603542?dopt=Citation>

APA

Seki, E., Samuele, D. M., Gwak, G-Y., Kluwe, J., Inokuchi, S., Bursill, C. A., Llovet, J. M., Brenner, D. A., & Schwabe, R. F. (2009). CCR1 and CCR5 promote hepatic fibrosis in mice. J CLIN INVEST, 119(7), 1858-1870. [7]. http://www.ncbi.nlm.nih.gov/pubmed/19603542?dopt=Citation

Vancouver

Seki E, Samuele DM, Gwak G-Y, Kluwe J, Inokuchi S, Bursill CA et al. CCR1 and CCR5 promote hepatic fibrosis in mice. J CLIN INVEST. 2009;119(7):1858-1870. 7.

Bibtex

@article{f031490a82fc4cc3a99d905f99e0203e,
title = "CCR1 and CCR5 promote hepatic fibrosis in mice.",
abstract = "Hepatic fibrosis develops as a response to chronic liver injury and almost exclusively occurs in a proinflammatory environment. However, the role of inflammatory mediators in fibrogenic responses of the liver is only poorly understood. We therefore investigated the role of CC chemokines and their receptors in hepatic fibrogenesis. The CC chemokines MIP-1alpha, MIP-1beta, and RANTES and their receptors CCR1 and CCR5 were strongly upregulated in 2 experimental mouse models of fibrogenesis. Neutralization of CC chemokines by the broad-spectrum CC chemokine inhibitor 35k efficiently reduced hepatic fibrosis, and CCR1- and CCR5-deficient mice displayed substantially reduced hepatic fibrosis and macrophage infiltration. Analysis of fibrogenesis in CCR1- and CCR5-chimeric mice revealed that CCR1 mediates its profibrogenic effects in BM-derived cells, whereas CCR5 mediates its profibrogenic effects in resident liver cells. CCR5 promoted hepatic stellate cell (HSC) migration through a redox-sensitive, PI3K-dependent pathway. Both CCR5-deficient HSCs and CCR1- and CCR5-deficient Kupffer cells displayed strong suppression of CC chemokine-induced migration. Finally, we detected marked upregulation of RANTES, CCR1, and CCR5 in patients with hepatic cirrhosis, confirming activation of the CC chemokine system in human fibrogenesis. Our data therefore support a role for the CC chemokine system in hepatic fibrogenesis and suggest distinct roles for CCR1 and CCR5 in Kupffer cells and HSCs.",
keywords = "Animals, Humans, Male, inhibitors, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Cell Movement, Kupffer Cells physiology, Liver Cirrhosis, Experimental etiology, Receptors, CCR1 antagonists, Receptors, CCR5 antagonists, Animals, Humans, Male, inhibitors, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Cell Movement, Kupffer Cells physiology, Liver Cirrhosis, Experimental etiology, Receptors, CCR1 antagonists, Receptors, CCR5 antagonists",
author = "Ekihiro Seki and Samuele, {De Minicis} and Geum-Youn Gwak and Johannes Kluwe and Sayaka Inokuchi and Bursill, {Christina A} and Llovet, {Josep M} and Brenner, {David A} and Schwabe, {Robert F}",
year = "2009",
language = "Deutsch",
volume = "119",
pages = "1858--1870",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "7",

}

RIS

TY - JOUR

T1 - CCR1 and CCR5 promote hepatic fibrosis in mice.

AU - Seki, Ekihiro

AU - Samuele, De Minicis

AU - Gwak, Geum-Youn

AU - Kluwe, Johannes

AU - Inokuchi, Sayaka

AU - Bursill, Christina A

AU - Llovet, Josep M

AU - Brenner, David A

AU - Schwabe, Robert F

PY - 2009

Y1 - 2009

N2 - Hepatic fibrosis develops as a response to chronic liver injury and almost exclusively occurs in a proinflammatory environment. However, the role of inflammatory mediators in fibrogenic responses of the liver is only poorly understood. We therefore investigated the role of CC chemokines and their receptors in hepatic fibrogenesis. The CC chemokines MIP-1alpha, MIP-1beta, and RANTES and their receptors CCR1 and CCR5 were strongly upregulated in 2 experimental mouse models of fibrogenesis. Neutralization of CC chemokines by the broad-spectrum CC chemokine inhibitor 35k efficiently reduced hepatic fibrosis, and CCR1- and CCR5-deficient mice displayed substantially reduced hepatic fibrosis and macrophage infiltration. Analysis of fibrogenesis in CCR1- and CCR5-chimeric mice revealed that CCR1 mediates its profibrogenic effects in BM-derived cells, whereas CCR5 mediates its profibrogenic effects in resident liver cells. CCR5 promoted hepatic stellate cell (HSC) migration through a redox-sensitive, PI3K-dependent pathway. Both CCR5-deficient HSCs and CCR1- and CCR5-deficient Kupffer cells displayed strong suppression of CC chemokine-induced migration. Finally, we detected marked upregulation of RANTES, CCR1, and CCR5 in patients with hepatic cirrhosis, confirming activation of the CC chemokine system in human fibrogenesis. Our data therefore support a role for the CC chemokine system in hepatic fibrogenesis and suggest distinct roles for CCR1 and CCR5 in Kupffer cells and HSCs.

AB - Hepatic fibrosis develops as a response to chronic liver injury and almost exclusively occurs in a proinflammatory environment. However, the role of inflammatory mediators in fibrogenic responses of the liver is only poorly understood. We therefore investigated the role of CC chemokines and their receptors in hepatic fibrogenesis. The CC chemokines MIP-1alpha, MIP-1beta, and RANTES and their receptors CCR1 and CCR5 were strongly upregulated in 2 experimental mouse models of fibrogenesis. Neutralization of CC chemokines by the broad-spectrum CC chemokine inhibitor 35k efficiently reduced hepatic fibrosis, and CCR1- and CCR5-deficient mice displayed substantially reduced hepatic fibrosis and macrophage infiltration. Analysis of fibrogenesis in CCR1- and CCR5-chimeric mice revealed that CCR1 mediates its profibrogenic effects in BM-derived cells, whereas CCR5 mediates its profibrogenic effects in resident liver cells. CCR5 promoted hepatic stellate cell (HSC) migration through a redox-sensitive, PI3K-dependent pathway. Both CCR5-deficient HSCs and CCR1- and CCR5-deficient Kupffer cells displayed strong suppression of CC chemokine-induced migration. Finally, we detected marked upregulation of RANTES, CCR1, and CCR5 in patients with hepatic cirrhosis, confirming activation of the CC chemokine system in human fibrogenesis. Our data therefore support a role for the CC chemokine system in hepatic fibrogenesis and suggest distinct roles for CCR1 and CCR5 in Kupffer cells and HSCs.

KW - Animals

KW - Humans

KW - Male

KW - inhibitors

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Cell Movement

KW - Kupffer Cells physiology

KW - Liver Cirrhosis, Experimental etiology

KW - Receptors, CCR1 antagonists

KW - Receptors, CCR5 antagonists

KW - Animals

KW - Humans

KW - Male

KW - inhibitors

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Cell Movement

KW - Kupffer Cells physiology

KW - Liver Cirrhosis, Experimental etiology

KW - Receptors, CCR1 antagonists

KW - Receptors, CCR5 antagonists

M3 - SCORING: Zeitschriftenaufsatz

VL - 119

SP - 1858

EP - 1870

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 7

M1 - 7

ER -