Direct effects of interleukin-6 on liver progenitor oval cells in culture

Research output: Contribution to journalArticle

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Abstract

Following acute injury, liver is usually regenerated from hepatocytes by a process that is dependent on interleukin (IL)-6. If this pathway is impaired, restoration of the liver mass and ultimately the survival of the animal are dependent on recruitment of cells from a precursor cell population, either a stem cell or an oval cell. Importantly, oval cells are also implicated in tumorigenesis. A carcinogenic choline-deficient ethionine supplemented (CDE) diet is capable of inducing substantial numbers of oval cells that we can isolate and utilize to identify cytokines, which affect oval cell proliferation and differentiation. Currently, a putative role of IL-6 in oval cell biology is suggested by the elevation of IL-6 in liver and serum of mice treated with a CDE diet and knockout mouse studies. Also, when IL-6 is injected into the peritoneal cavity of mice on the CDE diet, oval cell numbers are increased compared to mice on the CDE diet alone. We investigated the role of human IL-6 on p53 null immortalized murine oval cell lines (PIL), finding that they express transcripts for the IL-6 receptor and gp130, STAT-3 is phosphorylated upon IL-6 stimulation, IL-6 induces IL-6 production, and proliferation is induced by IL-6. In addition, we show that mouse primary oval cells also express IL-6 receptor and gp130 mRNA. These findings suggest that IL-6 directly stimulates oval cells and an autocrine mechanism may sustain oval cell proliferation.
Original languageEnglish
Pages (from-to)650-656
JournalWound Repair and Regeneration
Volume12
Issue number6
DOIs
Publication statusPublished - 2004

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Interleukin-6
Stem Cells
Cell Culture Techniques
Liver
Diet
Interleukin-6 Receptors
Cell Count
Cell Proliferation
Ethionine
Peritoneal Cavity
Choline
Knockout Mice
Cell Biology
Cell Differentiation
Hepatocytes
Carcinogenesis
Cytokines
Cell Line
Messenger RNA
Wounds and Injuries

Cite this

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title = "Direct effects of interleukin-6 on liver progenitor oval cells in culture",
abstract = "Following acute injury, liver is usually regenerated from hepatocytes by a process that is dependent on interleukin (IL)-6. If this pathway is impaired, restoration of the liver mass and ultimately the survival of the animal are dependent on recruitment of cells from a precursor cell population, either a stem cell or an oval cell. Importantly, oval cells are also implicated in tumorigenesis. A carcinogenic choline-deficient ethionine supplemented (CDE) diet is capable of inducing substantial numbers of oval cells that we can isolate and utilize to identify cytokines, which affect oval cell proliferation and differentiation. Currently, a putative role of IL-6 in oval cell biology is suggested by the elevation of IL-6 in liver and serum of mice treated with a CDE diet and knockout mouse studies. Also, when IL-6 is injected into the peritoneal cavity of mice on the CDE diet, oval cell numbers are increased compared to mice on the CDE diet alone. We investigated the role of human IL-6 on p53 null immortalized murine oval cell lines (PIL), finding that they express transcripts for the IL-6 receptor and gp130, STAT-3 is phosphorylated upon IL-6 stimulation, IL-6 induces IL-6 production, and proliferation is induced by IL-6. In addition, we show that mouse primary oval cells also express IL-6 receptor and gp130 mRNA. These findings suggest that IL-6 directly stimulates oval cells and an autocrine mechanism may sustain oval cell proliferation.",
author = "Vance Matthews and E. Klinken and George Yeoh",
year = "2004",
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volume = "12",
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Direct effects of interleukin-6 on liver progenitor oval cells in culture. / Matthews, Vance; Klinken, E.; Yeoh, George.

In: Wound Repair and Regeneration, Vol. 12, No. 6, 2004, p. 650-656.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Direct effects of interleukin-6 on liver progenitor oval cells in culture

AU - Matthews, Vance

AU - Klinken, E.

AU - Yeoh, George

PY - 2004

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N2 - Following acute injury, liver is usually regenerated from hepatocytes by a process that is dependent on interleukin (IL)-6. If this pathway is impaired, restoration of the liver mass and ultimately the survival of the animal are dependent on recruitment of cells from a precursor cell population, either a stem cell or an oval cell. Importantly, oval cells are also implicated in tumorigenesis. A carcinogenic choline-deficient ethionine supplemented (CDE) diet is capable of inducing substantial numbers of oval cells that we can isolate and utilize to identify cytokines, which affect oval cell proliferation and differentiation. Currently, a putative role of IL-6 in oval cell biology is suggested by the elevation of IL-6 in liver and serum of mice treated with a CDE diet and knockout mouse studies. Also, when IL-6 is injected into the peritoneal cavity of mice on the CDE diet, oval cell numbers are increased compared to mice on the CDE diet alone. We investigated the role of human IL-6 on p53 null immortalized murine oval cell lines (PIL), finding that they express transcripts for the IL-6 receptor and gp130, STAT-3 is phosphorylated upon IL-6 stimulation, IL-6 induces IL-6 production, and proliferation is induced by IL-6. In addition, we show that mouse primary oval cells also express IL-6 receptor and gp130 mRNA. These findings suggest that IL-6 directly stimulates oval cells and an autocrine mechanism may sustain oval cell proliferation.

AB - Following acute injury, liver is usually regenerated from hepatocytes by a process that is dependent on interleukin (IL)-6. If this pathway is impaired, restoration of the liver mass and ultimately the survival of the animal are dependent on recruitment of cells from a precursor cell population, either a stem cell or an oval cell. Importantly, oval cells are also implicated in tumorigenesis. A carcinogenic choline-deficient ethionine supplemented (CDE) diet is capable of inducing substantial numbers of oval cells that we can isolate and utilize to identify cytokines, which affect oval cell proliferation and differentiation. Currently, a putative role of IL-6 in oval cell biology is suggested by the elevation of IL-6 in liver and serum of mice treated with a CDE diet and knockout mouse studies. Also, when IL-6 is injected into the peritoneal cavity of mice on the CDE diet, oval cell numbers are increased compared to mice on the CDE diet alone. We investigated the role of human IL-6 on p53 null immortalized murine oval cell lines (PIL), finding that they express transcripts for the IL-6 receptor and gp130, STAT-3 is phosphorylated upon IL-6 stimulation, IL-6 induces IL-6 production, and proliferation is induced by IL-6. In addition, we show that mouse primary oval cells also express IL-6 receptor and gp130 mRNA. These findings suggest that IL-6 directly stimulates oval cells and an autocrine mechanism may sustain oval cell proliferation.

U2 - 10.1111/j.1067-1927.2004.12605.x

DO - 10.1111/j.1067-1927.2004.12605.x

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