Cytokine-induced neutrophil chemoattractant-1 is released by the noninjured liver in a rat acute-phase model.
The source of serum cytokine-induced neutrophil chemoattractant (CINC-1) and consequences of its presence in the tissue of synthesis have not been clearly elucidated under acute-phase situation. To pursue this question, turpentine oil (TO) was intramuscularly injected into rats, and RNA and local protein levels of acute-phase cytokines and of CINC-1 were studied in the TO injected gluteal muscle, as well as in noninjured muscle, in the liver, kidney, lung and spleen. The serum levels of acute-phase mediators and of CINC-1 were measured together with total leukocyte subpopulations. Recruitment of inflammatory cells in muscle and in the other organs was investigated by quantitative immunohistochemical methods. The effect of acute-phase mediators, including interferon gamma (IFN-gamma) on the synthesis of CINC-1 in cultured hepatocytes was also investigated at the RNA and protein level. We found that the sera of the TO-treated rats contained elevated levels of IL-6, IL-1beta and CINC-1. Increased serum levels of IFN-gamma were also observed not only in the injured muscle but also and to a higher extent in the liver. However, while neutrophils and mononuclear phagocytes were found in the injured muscle, no inflammatory cells were detected at the non-'inflamed' site, namely, the liver or in the other organs. In vitro, treatment of cultured hepatocytes with IL-1beta led to elevated CINC-1 gene expression. This was true to a lesser extent upon IL-6 and tumor necrosis factor (TNF-alpha) exposure. Interestingly, IFN-gamma did not effect CINC-1 gene expression. These results indicate that CINC-1 behaves as an acute-phase protein and its expression is inducible in hepatocytes. However, CINC-1-production in the liver does not lead to recruitment of inflammatory cells into the organ.
Sheikh
Nadeem
N
Department of Internal Medicine, Division of Gastroenterology and Endocrinology, University Hospital Göttingen, Göttingen, Germany.
Tron
Kyrylo
K
Dudas
Jozsef
J
Ramadori
Giuliano
G
D000210:Acute-Phase Reaction / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003402:Creatine Kinase / Q000097:blood; D016207:Cytokines / Q000502:physiology*; D017931:DNA Primers; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D017931:DNA Primers; D016209:Interleukin-8; D003402:Creatine Kinase