Toll-like receptor stimulation differentially regulates vasoactive intestinal peptide type 2 receptor in macrophages
Herrera, Juan Luis
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CitationHerrera, Juan Luis, Elena Gonzalez-Rey, Rafael Fernandez-Montesinos, Francisco J Quintana, Rafael Najmanovich, and David Pozo. 2009. “Toll-like receptor stimulation differentially regulates vasoactive intestinal peptide type 2 receptor in macrophages.” Journal of Cellular and Molecular Medicine 13 (9b): 3209-3217. doi:10.1111/j.1582-4934.2009.00662.x. http://dx.doi.org/10.1111/j.1582-4934.2009.00662.x.
AbstractVasoactive intestinal peptide (VIP) was originally isolated as a vasodilator intestinal peptide, then as a neuropeptide. In the immune system, VIP is described as an endogenous macrophage-deactivating factor. VIP exerts its immunological actions in a paracrine and/or autocrine manner, through specific receptors. However, very little is known about the molecular regulation of VIP type 2 receptor (VPAC2) in the immune system. We now report that different toll-like receptor (TLR) ligands selectively regulate the VPAC2 receptor gene and show a gene repression system controlled by key protein kinase signalling cascades in macrophages. VPAC2 gene expression is regulated by gram-positive (TLR2 ligands) and gram-negative bacteria wall constituents (TLR4 ligands). Moreover, VPAC2 is tightly regulated: TLR2- or TLR2/6- but not TLR2/1-mediated mechanisms are responsible for the induction of VPAC2. TLR stimulation by viral or bacterial nucleic acids did not modify the VPAC2 mRNA levels. Remarkably, imiquimod – a synthetic TLR7 ligand – led to a potent up-regulation of VPAC2 gene expression. TLR5 stimulation by flagellin present in gram-positive and gram-negative bacteria did not affect VPAC2 mRNA. The p38 mitogen-activated protein kinase (MAPK) activity accounted for the TLR4-mediated induction of VPAC2 gene expression. Surprisingly, our data strongly suggest for the first time a tightly repressed control of VPAC2 mRNA induction by elements downstream of MAPK kinase 1/2, PI3K/Akt, and particularly Jun-NH2-terminal kinase signalling pathways.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:21461998
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