Receptors and transcriptional factors involved in the anti-inflammatory activity of VIP and PACAP.
In: Annals of the New York Academy of Sciences, Jg. 921 (2000), S. 92-102
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Zugriff:
VIP and PACAP modulate the function of inflammatory cells through specific receptors. VIP/PACAP inhibit the production of TNF alpha, IL-6, IL-12, and nitric oxide (NO), and stimulate IL-10 in peritoneal macrophages and Raw 264.7 cells. Here we report on the specific VIP/PACAP receptors, transduction pathways, and transcriptional factors involved in the regulation of these macrophage factors by VIP and PACAP. Both neuropeptides inhibit IL-6 production mainly through PAC1 binding, PKC activation, and the subsequent shedding of the LPS receptor CD14 in macrophages. However, the effects on TNF alpha, IL-10, IL-12, and NO are mostly mediated through the constitutively expressed VPAC1 receptor, although the inducible expressed VPAC2 may also participate. VIP/PACAP binding to VPAC1 induces both a cAMP-dependent and a cAMP-independent pathways that regulate cytokine and NO production at the transcriptional level. VIP/PACAP inhibit TNF alpha through reduction in NFkB binding and changes in the composition of CRE-binding complexes; they inhibit IL-12 through reduction in NFkB binding and changes in the composition of the ets-2 complexes. VIP/PACAP inhibit iNOS expression through reduction in NFkB and IRF-1 binding, and augment IL-10 by increasing CREB-binding. Whereas the inhibition of IRF-1 and CRE-binding complexes seems to be mediated through the cAMP-dependent pathway, VIP/PACAP inhibition of NFkB nuclear translocation is mediated through a reduction in IkB alpha degradation mediated by the cAMP-independent pathway. This study provides new evidence for the understanding of the molecular mechanism by means of which VIP and PACAP attenuate the inflammatory response.
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Receptors and transcriptional factors involved in the anti-inflammatory activity of VIP and PACAP.
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Autor/in / Beteiligte Person: | Leceta, J ; Gomariz, RP ; Martinez, C ; Abad, C ; Ganea, D ; Delgado, M |
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Zeitschrift: | Annals of the New York Academy of Sciences, Jg. 921 (2000), S. 92-102 |
Veröffentlichung: | 2006- : New York, NY : Malden, MA : New York Academy of Sciences ; Blackwell ; <i>Original Publication</i>: New York, The Academy., 2000 |
Medientyp: | academicJournal |
ISSN: | 0077-8923 (print) |
DOI: | 10.1111/j.1749-6632.2000.tb06954.x |
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