Regulatory mechanisms of interleukin-8 production induced by tumour necrosis factor-α in human hepatocellular carcinoma cells.
Bottom Line: Tumour necrosis factor-α (TNF-α) significantly induced phosphorylation of p38 MAPK, ERK, Akt and production of IL-8 from HCC cells, which were prevented by SB203580 (p38 MAPK inhibitor), PD98059 (ERK inhibitor), LY294002 and Wortmannin (PI3K inhibitor) and SB328437 (CCR3 inhibitor).TNF-α could significantly increase the translocation of NF-κB p65 protein into the nucleus in a dose-dependent manner, while SB203580 partially inhibited.There was a potential cross-talking between receptors.
Affiliation: Liver Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, China.Show MeSH
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Mentions: Dynamic alternations of total, stable, differentiated and dead cell number were measured and recorded every 5 min. for 24 hrs after a 24 hrs pre-treatment with those inhibitors at 5 μM and TNF-α at 1 ng/ml, respectively, or 1 hr pre-treatment with those inhibitors 5 μM followed by the challenge with TNF-α at 1 ng/ml. The increased rate of total cell number was significantly higher at SB203580 alone and lower at PD98059 alone as compared with controls, whereas the decreased rate of differentiated cell number was conversed (P < 0.05 or 0.01, respectively, in Fig. S2). The increased rate of dead cell number in control was significantly higher than that with TNF-α or inhibitors, of which the group with LY294002 had significantly higher rate than that with TNF-α, Wortmmanin, SB203580 or PD98059 (Fig. 7). The increased rate of total cell number in groups with TNF-α and LY294002 or TNF-α and SB203580 was significantly higher than that in controls or TNF-α alone (P < 0.05 or 0.01, respectively), whereas the decreased rate of differentiated cell number showed opposite. The increased rates of stable or dead cell number in groups with TNF-α alone or TNF-α and PD98059 were higher. IL-8 induced a significant increase of cell proliferation at 48 and 72 hrs (Fig. S3), whereas TNF-α reduced cells proliferation from 24 hrs (Fig. S4).
Affiliation: Liver Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, China.