Abstract
In this study, we examined the role of fibrogenic cytokines in alcohol- induced fibrosis. In particular, we examined the production of a novel fibrogenic cytokine, fibrosin, among others, by fibroblasts in response to ethanol in vitro; we also studied the production of fibrosin in an animal model of alcohol-induced liver injury. This model system utilizes the intragastric feeding rat model in which rats are fed different dietary fats and ethanol or dextrose. Our study showed that physiologic concentrations of ethanol directly induced proliferation of fibroblasts in vitro and also stimulated the production of cytokines. In particular, fibrosin, the novel fibrogenic cytokine, was produced. Other cytokines such as TGFβ, IL-6, and TNFα were also induced. Also, exposure of fibroblasts to interleukin-1β, interleukin-6, and tumor necrosis factor α induced production of fibrosin. In the fish oil-ethanol-fed rats which showed fibrotic lesions in the liver, fibrosin mRNA as well as protein was expressed. Fibrosin was not detected in control rats not exhibiting fibrosis. These studies show that ethanol can directly stimulate fibroblast proliferation and production of fibrogenic cytokines. It is likely that fibrosin, which may be derived from inflammatory cells, contributes to alcohol-induced hepatic fibrosis in vivo.
| Original language | English |
|---|---|
| Pages (from-to) | 40-49 |
| Number of pages | 10 |
| Journal | Experimental and Molecular Pathology |
| Volume | 67 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Sept 1999 |
| Externally published | Yes |
Bibliographical note
Funding Information:In this study, we examined the role of fibrogenic cytokines in alcohol-induced fibrosis. In particular, we examined the production of a novel fibrogenic cytokine, fibrosin, among others, by fibroblasts in response to ethanol in vitro; we also studied the production of fibrosin in an animal model of alcohol-induced liver injury. This model system utilizes the intragastric feeding rat model in which rats are fed different dietary fats and ethanol or dextrose. Our study showed that physiologic concentrations of ethanol directly induced proliferation of fibroblasts in vitro and also stimulated the production of cytokines. In particular, fibrosin, the novel fibrogenic cytokine, was produced. Other cytokines such as TGFβ, IL-6, and TNFα were also induced. Also, exposure of fibroblasts to interleukin-1β, interleukin-6, and tumor necrosis factor α induced production of fibrosin. In the fish oil–ethanol-fed rats which showed fibrotic lesions in the liver, fibrosin mRNA as well as protein was expressed. Fibrosin was not detected in control rats not exhibiting fibrosis. These studies show that ethanol can directly stimulate fibroblast proliferation and production of fibrogenic cytokines. It is likely that fibrosin, which may be derived from inflammatory cells, contributes to alcohol-induced hepatic fibrosis in vivo. q 1999 Academic Press 1This research was supported in part by an American Cancer Society Research Professorship Grant ACS/PRP-55 awarded to Dr. P. W. Robbins.
ASJC Scopus Subject Areas
- Pathology and Forensic Medicine
- Molecular Biology
- Clinical Biochemistry
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't