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Proinflammatory cytokine effects on NO and hepatic progenitor cell differentiation
Author(s) -
Wright Natasha,
Fiza Babar,
Samuelson Lisa,
Walkup Maggie,
Gerber David A
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1135
Subject(s) - proinflammatory cytokine , downregulation and upregulation , progenitor cell , nitric oxide synthase , tumor necrosis factor alpha , hepatocyte , biology , immunology , stem cell , chemistry , microbiology and biotechnology , inflammation , nitric oxide , endocrinology , biochemistry , in vitro , gene
Background: TNF‐α inhibits hepatocyte apoptosis possibly by iNOS (inducible nitric oxide synthase). Yet some studies show iNOS is also a cell death trigger during early liver regeneration. Hepatic progenitor cells (HPC) from adult tissue are proliferative and bipotent but their ability to upregulate iNOS in response to proinflammatory cytokines is unknown. Aim: To investigate the impact of proinflammatory cytokines on iNOS and HPC survival and differentiation. Methods: HPC from adult mice were analyzed for iNOS expression during primary culture. HPC colonies were established in growth conditions supplemented with: TNF‐α; IL‐1β + TNF‐α; TGF‐β or IL‐1β. The colonies were analyzed for differentiation markers (albumin, AFP, CK 19) and iNOS upregulation at 20 hours, 3 and 7 days after supplementation. Results: HPC expression of iNOS occurs immediately after isolation but is lost by day 2 of culture. Supplementation with IL‐1β + TNF‐α in proliferating HPC yields a persistent upregulation of iNOS which is not seen after supplementation with individual cytokines. HPC express hepatic and biliary genes after culture with proinflammatory cytokines. Conclusions: iNOS is not routinely expressed during hepatic progenitor cell proliferation but can be induced in response to a combination of proinflammatory cytokines. Upregulation of iNOS expression does not lead to a loss of the bipotentiality of the HPC population.