title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Dermatology, Aarhus University Hospital, P. Orumsgade 11, 8000 Aarhus, Denmark.
authors.forename: M K
authors.initials: MK
authors.lastname: Rasmussen
authors.forename: L
authors.initials: L
authors.lastname: Iversen
authors.forename: C
authors.initials: C
authors.lastname: Johansen
authors.forename: J
authors.initials: J
authors.lastname: Finnemann
authors.forename: L S
authors.initials: LS
authors.lastname: Olsen
authors.forename: K
authors.initials: K
authors.lastname: Kragballe
authors.forename: Borbala
authors.initials: B
authors.lastname: Gesser
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000502:physiology*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D016209:Interleukin-8; D016328:NF-kappa B; C498143:RELA protein, human; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases