Regulation of the C-X-C chemokine, mob-1, gene expression in primary rat hepatocytes.
The chemokine, mob-1, is involved in inflammatory and immune responses and may be an important mediator of the inflammatory response in the liver. Here, we investigated the upstream signal pathways that could be involved in the regulation of mob-1 expression. We have found that in primary rat hepatocytes the isolation and subsequent culture of these cells induced mob-1 expression. A similar induction of mob-1 mRNA was observed when the hepatocytes were stimulated with interferon-gamma (IFN-gamma). When hepatocytes were stimulated with IFN-gamma or cytokine mixture (IFN-gamma, interleukin-1beta and tumour necrosis factor-alpha), c-Jun N-terminal kinase (JNK), p38 and extracellular-regulated kinase (ERK) were phosphorylated, suggesting an involvement of the mitogen-activated protein kinases (MAPK) in the induction of mob-1 expression. The p38 kinase inhibitor, SB 203580, and the NF-kappaB inhibitor, MG-132, inhibited the induction of mob-1 mRNA and the effects were not additive. These results demonstrate that in primary rat hepatocytes the transient induction of mob-1 expression was regulated by p38 kinase and NF-kappaB through a common regulatory pathway.
Varley
Claire L
CL
Biochemistry Research Division, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Armitage
Suzanne
S
Hassanshahiraviz
Gholamhossein
G
Dickson
Alan J
AJ
D000818:Animals; D015152:Blotting, Northern; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C091326:Cxcl10 protein, rat; D016207:Cytokines; D012333:RNA, Messenger; D020928:Mitogen-Activated Protein Kinases