Insulin-like growth factor-1 downregulates nuclear factor kappa B activation and upregulates interleukin-8 gene expression induced by tumor necrosis factor alpha.
Pretreatment of HT29-D4 epithelial adenocarcinoma colic cells with des-IGF-1 upregulated TNF alpha-mediated activation of IL-8 expression at different levels (protein, mRNA, and hnRNA). RNA transcription but not RNA stabilization was found to be involved. In this cell line, cooperation of NF-kappa B with other factors appeared essential for IL-8 expression. Indeed, TNF alpha-induced NF-kappa B translocation was not sufficient to support enhancement of the transcription and des-IGF-1 did not promote but partly inhibited both the TNF alpha-induced NF-kappa B activation and I kappa B alpha degradation through a PI-3K-dependent pathway. A CCAAT/enhancer binding protein (C/EBP) site located on the IL-8 gene enhancer cooperated with a NF-kappa B binding site and led to the upregulation of IL-8 expression. Binding of C/EBP alpha to this sequence disappeared in IGF-1 treated cells. This event may be important for the cross-talk between IGF-1- and TNF alpha-mediated pathways leading to the control of inflammatory processes and the decision concerning apoptosis or cell survival.
Vallée
Sébastien
S
Laboratoire de Biochimie Cellulaire, UMR 6032 CNRS, Faculté de Pharmacie, 27 Bd Jean Moulin, F-13385 Marseille, France.
Fouchier
Francis
F
Brémond
Patricia
P
Briand
Claudette
C
Marvaldi
Jacques
J
Champion
Serge
S
D000230:Adenocarcinoma; D000546:Amanitins / Q000494:pharmacology; D001665:Binding Sites; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D003110:Colonic Neoplasms; D015536:Down-Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D007700:Kinetics; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D018808:Transcription Factor AP-1 / Q000502:physiology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D015854:Up-Regulation
D000546:Amanitins; D022763:CCAAT-Enhancer-Binding Protein-alpha; D022762:CCAAT-Enhancer-Binding Proteins; D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D010446:Peptide Fragments; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C058957:insulin-like growth factor 1, des-(1-3)-; D000072000:NF-KappaB Inhibitor alpha; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases