Insulin-like growth factor-1 downregulates nuclear factor κB activation and upregulates interleukin-8 gene expression induced by tumor necrosis factor α

• Published in: Biochemical and biophysical research communications Vol. 305; no. 4; pp. 831 - 839
• Main Authors: Vallée, Sébastien, Fouchier, Francis, Brémond, Patricia, Briand, Claudette, Marvaldi, Jacques, Champion, Serge
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.06.2003; Elsevier
• Subjects: Adenocarcinoma; Amanitins - pharmacology; Binding Sites; CCAAT-Enhancer-Binding Protein-alpha - metabolism; CCAAT-Enhancer-Binding Proteins - metabolism; CCAAT/enhancer binding protein; Colonic Neoplasms; Down-Regulation; Humans; I-kappa B Proteins - metabolism; Insulin-Like Growth Factor I - pharmacology; Insulin-like growth factor-1; Interleukin-8; Interleukin-8 - biosynthesis; Interleukin-8 - genetics; Kinetics; Life Sciences; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; Nuclear factor κB; Peptide Fragments - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; RNA, Messenger - biosynthesis; Transcription Factor AP-1 - physiology; Transcriptional Activation; Tumor Cells, Cultured; Tumor necrosis factor α; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - pharmacology; Up-Regulation; Insulin-like growth factor-1; Interleukin-8; Tumor necrosis factor α; Nuclear factor κB; CCAAT/enhancer binding protein
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(03)00866-0

Pretreatment of HT29-D4 epithelial adenocarcinoma colic cells with des-IGF-1 upregulated TNFα-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-κB with other factors appeared essential for IL-8 expression. Indeed, TNFα-induced NF-κB translocation was not sufficient to support enhancement of the transcription and des-IGF-1 did not promote but partly inhibited both the TNFα-induced NF-κB activation and IκBα 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-κB binding site and led to the upregulation of IL-8 expression. Binding of C/EBPα to this sequence disappeared in IGF-1 treated cells. This event may be important for the cross-talk between IGF-1- and TNFα-mediated pathways leading to the control of inflammatory processes and the decision concerning apoptosis or cell survival.