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-1 transcript levels, suggesting that the increase in sICAM-1 may involve post-transcriptional/translational 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.
Sapna
S
S
Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695 011, Kerala, India.
Shivakumar
K
K
D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008301:Maleimides / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D011493:Protein Kinase C / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013373:Substance P / Q000502:physiology*
D005419:Flavonoids; D007211:Indoles; D008301:Maleimides; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D013373:Substance P; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C070515:bisindolylmaleimide I; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one