IL-8 and p53 are inversely regulated through JNK, p38 and NF-[kappa]B p65 in HepG2 cells during an inflammatory response

• Published in: Inflammation research Vol. 57; no. 7; p. 329
• Main Authors: Rasmussen, M K, Iversen, L, Johansen, C, Finnemann, J, Olsen, L S, Kragballe, K, Gesser, Borbala
• Format: Journal Article
• Language: English
• Published: New York Springer Nature B.V 01-07-2008
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-007-7220-1

It is reported that Nuclear factor-κB (NF-κB) activation is dysregulated in chronic inflammatory diseases like psoriasis, rheumatoid arthritis and cancer, resulting in an over expression of pro-inflammatory cytokines and an inhibition of apoptosis. We studied NF-κB activation and the induction of interleukin 8 (IL-8) and p53 gene expression in an interleukin 1β (IL-1β) stimulated HepG2 cell line. NF-κB induced IL-8 and p53 protein production was studied using specific siRNA, an IκB kinase 2 inhibitor, and mitogen activated protein kinase (MAPK) inhibitors. Results were analyzed by different techniques including Western blotting and ELISA. IL-1β induced both the IL-8 and p53 mRNA expression and protein production of IL-8, but not p53. Knockdown of NF-κB p65 expression with siRNA strongly reduced IL-8 production and significantly induced protein levels of p53. An IκB kinase 2 inhibitor, sc514, also strongly reduced IL-8 and significantly induced p53 protein levels. Using three MAPK inhibitors we showed that p38 MAPK and JNK dependent mechanisms are involved in the regulation of the IL-8 and p53 protein expression. Our results indicate that IL-8 and p53 protein expression is regulated through inverse activation of the p38 MAPK and the JNK pathways and the NF-κB p65 expression. [PUBLICATION ABSTRACT]