IL-8 and p53 are inversely regulated through JNK, p38 and NF-kappaB p65 in HepG2 cells during an inflammatory response.

Abstract

OBJECTIVE:

It is reported that Nuclear factor-kappaB (NF-kappaB) 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-kappaB activation and the induction of interleukin 8 (IL-8) and p53 gene expression in an interleukin 1beta (IL-1beta) stimulated HepG2 cell line.

METHODS:

NF-kappaB induced IL-8 and p53 protein production was studied using specific siRNA, an IkappaB kinase 2 inhibitor, and mitogen activated protein kinase (MAPK) inhibitors. Results were analyzed by different techniques including Western blotting and ELISA.

RESULTS:

IL-1beta induced both the IL-8 and p53 mRNA expression and protein production of IL-8, but not p53. Knockdown of NF-kappaB p65 expression with siRNA strongly reduced IL-8 production and significantly induced protein levels of p53. An IkappaB 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.

CONCLUSION:

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-kappaB p65 expression.

• Authors: M K Rasmussen, L Iversen, C Johansen, J Finnemann, L S Olsen, K Kragballe, Borbala Gesser
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 57 Issue 7 Pg. 329-39 (Jul 2008) ISSN: 1023-3830 [Print] Switzerland
• PMID: 18607537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Interleukin-8
• NF-kappa B
• RELA protein, human
• RNA, Small Interfering
• Transcription Factor RelA
• Tumor Suppressor Protein p53
• p38 Mitogen-Activated Protein Kinases

Topics

• Cell Line
• Cell Nucleus (metabolism)
• Enzyme Inhibitors (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Gene Expression Regulation
• Humans
• Inflammation
• Interleukin-8 (physiology)
• Models, Biological
• NF-kappa B (metabolism)
• RNA, Small Interfering (metabolism)
• Time Factors
• Transcription Factor RelA (metabolism)
• Tumor Suppressor Protein p53 (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)