Tumor necrosis factor α (TNF-α)-induced RANTES chemokine expression via activation of NF-κB and p38 MAP kinase: roles of TNF-α in alcoholic liver diseases

Abstract

Background/Aims: Increased concentration of plasma TNF-correlates with the clinical course of alcoholic liver diseases. In addition, hepatic RANTES which migrates CD4 T lymphocytes to liver is increased in patients with alcoholic hepatitis. We investigated that roles of TNF -on RANTES expression in hepatocytes.Methods: HLE cells were treated with TNF-in the presence, or absence of several inhibitors. Enzyme-linked immunoassay and reverse transcriptase-polymerase chain reaction were performed for the measurement of protein production and mRNA of RANTES, respectively. Moreover, DNA-binding activity of NF-B was investigated using electrophoretic mobility shift assay. To exam effects of TNF-on RANTES gene expression, luciferase assay was performed. Results: TNF-clearly up-regulated RANTES expression in a time-dependent fashion andinduced DNA-binding activity of NF-B. Moreover, TNF--induced RANTES expression was completely inhibited by SB203580, but not calphostin C and wortmannin. Luciferase assay showed that TNF-increased RANTES gene expression and mutation of NF-B binding sites in the RANTES promoter ablated TNF-inducibility. Conclusions:We presented that RANTES was transcriptionally induced in human hepatoma cells by treatment with TNF-via activation of NF-B and p38 MAP kinase, presumably suggesting that TNF--induced expression of RANTES plays important roles in cell-mediated liver injury in alcoholic liver diseases.

Anti-inflammatory effect of fibrate protects from cisplatin-induced ARF

“…RANTES has been proposed as a major mediator of antigen-independent T lymphocyte activation and has been found expressed in T cells, macrophages, fibroblasts, vascular smooth muscle, endothelial cells, renal mesangial (30), and tubular epithelial cells (21). TNF-␣ can also transcriptionally stimulate RANTES expression via activation of NF-B and p38 MAP kinase (23). Our studies also showed for the first time that mRNA levels of chemokine receptors CCR1 and CCR5 mRNA were upregulated by cisplatin.…”

Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFκB

“…Although the expression of RANTES was first thought to be limited to active T cells, recent data have shown that it is produced by a variety of tissue types in response to specific stimuli. RANTES mRNA is expressed late (3-5 d) after activation of resting T cells, whereas in fibroblasts, renal epithelial, and mesangial cells, RANTES mRNA is quickly up-regulated by TNF-␣ stimulation (Hirano et al 2003;Ogura et al 2005).…”

Chemokine RANTES Promoter Dimorphisms and Hepatocellular Carcinoma Occurrence in Patients with Alcoholic or Hepatitis C Virus–Related Cirrhosis

“…Nevertheless, chronic ethanol consumption is characterized by an increase in the expression of a number of inflammatory cytokines. TNFa-induced protein and mRNA expression of RANTES in human hepatoma cells, possibly suggests that TNF plays a pivotal role in migration of inflammatory cells by RANTES to the liver in patients with alcoholic liver disease (30).…”