Substance P enhances soluble ICAM-1 release from adult rat,cardiac fibroblasts by a p42/44 MAPK- and PKC-mediated mechanism

Substance P, a pro-inflammatory neuropeptide, is released from cardiac peptidergic nerves under conditions like ischemia but whether it modulates inflammatory processes in the heart remains unexplored. This study demonstrates for the first time that substance P augments the production of the soluble form of intercellular adhesion molecule-1, sICAM-1, by adult rat cardiac fibroblasts. However, RT-PCR showed no concomitant increase in ICAM-I transcript levels, suggesting that the increase in sICAM-1 may involve post-transcriptional/transiational mechanisms. Use of pharmacological inhibitors revealed that the stimulatory effect of substance P on sICAM-1 production is mediated by p42/44 MAPK and protein kinase C. Preliminary experiments also showed that the neuropeptide stimulates the production of prostaglandin E-2 by cardiac fibroblasts. The findings support the postulation that substance P may modulate multiple inflammatory responses within the myocardium through release of pro-inflammatory mediators from resident fibroblasts. (c) 2007 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.