Expression of IP-10 Chemokine is Regulated by Pro-inflammatory Cytokines in Cultured Hepatocytes

Chemokines are classified in four distinct groups as cxc, cc, cx3c and c, dependingon the presence or absence of a motif called elr (arg-leu-glu) before the first cysteineresidue in their structure. cxc chemokines are also subdivided into elr+ and elk.increasing evidence has indicated the existence of a chemokine network in the liver which isinvolved in both physiological responses and, under certain circumstances, pathological andrepair processes following hepatic injury. the cxc chemokines playa major role in boththese processes, and much attention has been focused on their therapeutic applications toliver disease.the aim of this study was to examine the response of cultured hepatocytes to exogenousinflammatory cytokines (tnf-(alpha) and ifn-(gamma)) regarding expression of ip-10 and growthregulatory oncogen (gro) chemokines. in this study we employed western and northernanalysis to measure chemokines at the level of protein and mrna by hepatocytes inresponse to pro-inflammatory cytokines.we found that, the pro-inflammatory cytokines, tnf-(alpha) and ifn-(gamma), selectively stimulatedexpression of ip-10 but were without effect on gro. this confirms a potential directinvolvement of these cytokines in chemokine production by hepatocytes. thus, ifn-(gamma) andtnf-(alpha) may play a role in hepatic injury and inflammation and produce some of theirbiological effects by localized induction of chernokines by hepatocytes.given the similarity to an acute phase response, we were able to show that ifn-(gamma) andtnf-(alpha) mimicked the effects of cell isolation and culture on induction of ip-10 expression.further, evidence for linkages between ifn-(gamma) and tnf-a and liver injuries is seen in hepatitisc and hepatitis b in which increased levels oftnf-(alpha) and its soluble receptor were reported.