Regulatory mechanisms of interleukin‐8 production induced by tumour necrosis factor‐α in human hepatocellular carcinoma cells

<jats:title>Abstract</jats:title><jats:p>Interleukin (IL)‐8 plays the critical role in the initiation of micro‐environmental inflammation responsible for tumour growth and patient prognosis. This study aimed at investigating the molecular mechanisms of IL‐8 production from human hepatocellular carcinoma (HCC) cells. The levels of IL‐8 and phosphorylation of p38 mitogen‐activated protein kinase (MAPK), ERK1/2 and Akt in MHCC‐97H cells were measured by ELISA, Western blot and immunofluorescence. NF‐κB p65 protein nuclear translocation was determined by non‐radioactive NF‐κB p50/p65 transcription factor activity kit and cell bio‐behaviours were detected by the real‐time cell‐monitoring system. 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. In inflammatory micro‐environment, HCC auto‐produced IL‐8 through p38 MAPK, ERK and PI3K/Akt signalling pathways, where the p38 MAPK is a central factor to activate the NF‐κB pathway and regulate the expression of IL‐8 production. There was a potential cross‐talking between receptors.</jats:p>