1. Vasoactive intestinal peptide induces IL-8 production in human colonic epithelial cells via MAP kinase-dependent and PKA-independent pathways.
- Author
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Toumi F, Neunlist M, Denis MG, Oreshkova T, Laboisse CL, Galmiche JP, and Jarry A
- Subjects
- Cell Polarity, Colon cytology, Cyclic AMP-Dependent Protein Kinases, Dose-Response Relationship, Drug, Enzyme Inhibitors pharmacology, Epithelial Cells drug effects, Epithelial Cells metabolism, Flavonoids pharmacology, HT29 Cells, Humans, Imidazoles pharmacology, Interleukin-8 metabolism, Intestinal Mucosa cytology, Intestinal Mucosa drug effects, Intestinal Mucosa metabolism, MAP Kinase Signaling System physiology, Mitogen-Activated Protein Kinases antagonists & inhibitors, Pyridines pharmacology, RNA, Messenger biosynthesis, Colon drug effects, Colon metabolism, Interleukin-8 biosynthesis, Mitogen-Activated Protein Kinases metabolism, Protein Serine-Threonine Kinases metabolism, Vasoactive Intestinal Peptide pharmacology
- Abstract
Vasoactive intestinal peptide (VIP) has been shown to be a key regulator of intestinal epithelial functions such as mucus and chloride secretion, paracellular permeability, and cell proliferation. However, its regulatory role in intestinal epithelial chemokine production remains unknown. The aim of this study was (1) to determine whether VIP can modulate intestinal epithelial interleukin-8 (IL-8) production and (2) to identify intracellular mediators responsible for this effect. In the human colonic epithelial cell line HT29-Cl.16E, VIP stimulates IL-8 secretion dose-dependently and IL-8 mRNA level at 10(-9) M. The protein kinase A (PKA) inhibitor PKI did not abolish the effect of VIP. However, inhibition of the ERK1/2 and p38 MAPK pathways reduced the VIP-stimulated IL-8 secretion and mRNA level. Together, our results showed that VIP stimulates IL-8 production in intestinal epithelial cells via PKA-independent and MAPK-dependent pathways. These data suggest that VIPergic pathways can play an immunomodulatory role in intestinal epithelial cells, by regulating epithelial IL-8 secretion.
- Published
- 2004
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