مرکز منطقه ای اطلاع رساني علوم و فناوري -

چكيده لاتين :

Chemokines are classified in four distinct groups as CXC, CC, CX3C and C, depending on the presence or absence of a motif called ELR (Arg-Leu-Glu) before the first cysteine residue 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 is involved in both physiological responses and, under certain circumstances, pathological and repair processes following hepatic injury. The CXC chemokines playa major role in both these processes, and much attention has been focused on their therapeutic applications to liver disease. The aim of this study was to examine the response of cultured hepatocytes to exogenous inflammatory cytokines (TNF-(ALPHA) and IFN-(GAMMA)) regarding expression of IP-10 and growth regulatory oncogen (Gro) chemokines. In this study we employed western and northern analysis to measure chemokines at the level of protein and mRNA by hepatocytes in response to pro-inflammatory cytokines. We found that, the pro-inflammatory cytokines, TNF-(ALPHA) and IFN-(GAMMA), selectively stimulated expression of IP-10 but were without effect on Gro. This confirms a potential direct involvement of these cytokines in chemokine production by hepatocytes. Thus, IfN-(GAMMA) and TNF-(ALPHA) may play a role in hepatic injury and inflammation and produce some of their biological effects by localized induction of chernokines by hepatocytes. Given the similarity to an acute phase response, we were able to show that IFN-(GAMMA) and TNF-(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 hepatitis C and hepatitis B in which increased levels ofTNF-(ALPHA) and its soluble receptor were reported.