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Inflammation Research

, Volume 57, Issue 7, pp 329–339 | Cite as

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

  • M. K. Rasmussen
  • L. Iversen
  • C. Johansen
  • J. Finnemann
  • L. S. Olsen
  • K. Kragballe
  • Borbala Gesser
Article

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.

Keywords:

JNK P38 MAPK IL-8 P53 NF-κB p65 

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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Copyright information

© Birkhaueser 2008

Authors and Affiliations

  • M. K. Rasmussen
    • 1
  • L. Iversen
    • 1
  • C. Johansen
    • 1
  • J. Finnemann
    • 2
  • L. S. Olsen
    • 2
  • K. Kragballe
    • 1
  • Borbala Gesser
    • 1
  1. 1.Department of DermatologyAarhus University HospitalAarhusDenmark
  2. 2.LEO PharmaBallerupDenmark

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