Vasoactive intestinal peptide induces IL-8 production in human colonic epithelial cells via MAP kinase-dependent and PKA-independent pathways.
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.
Toumi
Férial
F
INSERM U539, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes Cedex 01, France.
Neunlist
Michel
M
Denis
Marc G
MG
Oreshkova
Tsvetelina
T
Laboisse
Christian L
CL
Galmiche
Jean-Paul
JP
Jarry
Anne
A
D016764:Cell Polarity; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D016209:Interleukin-8; D011725:Pyridines; D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one