Induction of CINC (interleukin-8) production in rat liver by non-parenchymal cells.
The production of interleukin-8 (CINC: cytokine-induced neutrophil chemo-attractant) from different cell populations in the rat liver was studied and cells related to the initiation of CINC production in lipopolysaccharide (LPS)-injected endotoxaemic rats were characterized. Sinusoidal endothelial cells (16.4 +/- 10.6 ng/mL) produced significantly higher amounts of CINC in 24 h primary cultures compared with hepatocytes (0.9 +/- 0.9 ng/mL; P < 0.05) and Kupffer cells (6.5 +/- 5.1 ng/mL; P < 0.05). Lipopolysaccharide, tumour necrosis factor-alpha (TNF-alpha), and interleukin-1 alpha (IL-1 alpha) stimulated different liver cell populations to produce CINC; LPS mainly stimulated Kupffer cells. TNF-alpha stimulated hepatocytes and IL-1 alpha stimulated all three types of cells. Intraperitoneal injection of LPS (4 mg/kg) caused CINC accumulation in non-parenchymal cells of the rat liver within 1 h of injection, as shown by immunohistochemical staining. In contrast, CINC-positive hepatocytes were not seen until 3 h after injection of LPS. Ethanol was not a direct inducer of CINC production by rat hepatocytes in vitro. These findings strongly suggest that non-parenchymal liver cells, including sinusoidal endothelial cells, are the main source of CINC. Our data also suggest that during endotoxaemia, CINC production is initiated by non-parenchymal cells and this is followed by production from hepatocytes.
Third Department of Internal Medicine, Ehime University School of Medicine, Japan. keohkubo@shikoku.ne.jp
K
K
Ohkubo
T
T
Masumoto
N
N
Horiike
M
M
Onji
D000818:Animals; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000378:metabolism*; D002630:Chemotactic Factors / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D006131:Growth Inhibitors / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006131:Growth Inhibitors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol