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Rat hepatic stellate cells produce cytokine-induced neutrophil chemoattractant in culture and in vivo

Abstract Hepatic stellate cells are widely recognized for their contribution to liver fibrosis. This study investigated whether these cells also promote hepatic inflammation by producing neutrophil chemoattractants. Specifically, stellate cells were examined as potential sources of cytokine-induced neutrophil chemoattractant (CINC), a rat chemokine resembling human interleukin-8. Stellate cells from normal rat liver expressed little or no CINC. In culture, CINC mRNA was induced rapidly, coinciding with the phenomenon of culture activation. CINC mRNA rose 4.6-fold within 3 days and was accompanied by secretion of immunoreactive and biologically active CINC protein (4.1 ng ⋅ μg DNA −1 ⋅ day −1 ). Studies in vivo demonstrated that CINC could be induced in stellate cells during liver injury. CINC mRNA rose significantly (4- to 6-fold) in two models of liver disease, both of which cause stellate cell activation. In summary, the data indicate that CINC is induced during stellate cell activation in culture and in vivo. They suggest that stellate cell-derived CINC can promote hepatic inflammation in vivo. chemokine chemotaxis leukocyte inflammation Footnotes Address for reprint requests: J. J. Maher, Liver Center Laboratory, San Francisco General Hospital, Bldg. 40, Rm. 4102, 1001 Potrero Ave., San Francisco, CA 94110. This work was supported by National Institutes of Health Grants AA-07810, AA-00215, and DK-26743 and the Alcoholic Beverage Medical Research Foundation. Portions of this work appeared earlier in abstract form ( Hepatology 24: 353A, 1996). Copyright © 1998 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Gastrointestinal and Liver Physiology The American Physiological Society

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