Fibrosin: A novel lymphokine in alcohol-induced fibrosis.
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 TGFbeta, IL-6, and TNFalpha were also induced. Also, exposure of fibroblasts to interleukin-1beta, interleukin-6, and tumor necrosis factor alpha 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.
Prakash
S
S
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, Massachusetts.
Nanji
A A
AA
Robbins
P W
PW
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D017931:DNA Primers; D008222:Lymphokines; D012333:RNA, Messenger; C092591:fibrosin; D000431:Ethanol; D003094:Collagen