Abstract.
Objective:
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.
Methods:
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.
Results:
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.
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-κB p65 expression.
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Abbreviations
- HepG2:
-
human hepatocarcinoma cell
- NF-κB:
-
Nuclear transcription factor κB
- siRNA:
-
small interfering RNA
- IKK:
-
IκB kinase
- MAPK:
-
mitogen activated protein kinases
- JNK:
-
JUN-N-terminal protein kinase
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Received 13 November 2007; returned for revision 13 December 2007; received from final revision 4 January 2008; accepted by J. Di Battista 16 January 2008
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Rasmussen, M.K., Iversen, L., Johansen, C. et al. IL-8 and p53 are inversely regulated through JNK, p38 and NF-κB p65 in HepG2 cells during an inflammatory response. Inflamm. res. 57, 329–339 (2008). https://doi.org/10.1007/s00011-007-7220-1
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DOI: https://doi.org/10.1007/s00011-007-7220-1