Research Paper
Subject Category: Immunopharmacology and inflammation
British Journal of Pharmacology (2008) 154, 144–152; doi:10.1038/bjp.2008.50; published online 18 February 2008
A novel activity for substance P: stimulation of peroxisome proliferator-activated receptor-
protein expression in human monocytes and macrophages
A Amoruso1, C Bardelli1, G Gunella1, F Ribichini2 and S Brunelleschi1,3
- 1Department of Medical Sciences, School of Medicine, University of Piemonte Orientale 'A Avogadro', Novara, Italy
- 2Division of Cardiology, University of Verona, Verona, Italy
- 3IRCAD, University of Piemonte Orientale 'A Avogadro', Novara, Italy
Correspondence: Professor S Brunelleschi, Department of Medical Sciences, School of Medicine, University of Piemonte Orientale 'A Avogadro', Via Solaroli, 17, Novara 28100, Italy. E-mail: sandra.brunelleschi@med.unipmn.it
Received 14 November 2007; Accepted 28 January 2008; Published online 18 February 2008.
Abstract
Background and purpose:
Substance P (SP) and peroxisome proliferator-activated receptor-
(PPAR-) play important roles in different inflammatory conditions and are both expressed in human monocytes and macrophages. However, it is not known whether or not they interact. This study was undertaken to evaluate the effects of SP on PPAR- protein expression in monocytes and macrophages (MDMs: monocyte-derived macrophages) from healthy smokers and non-smokers.
Experimental approach:
PPAR- protein was detected by western blot and quantified by calculating the ratio between PPAR- and 
-actin protein expression. Constitutive tachykinin NK1 receptor expression in monocytes and MDMs from healthy smokers and non-smokers was evaluated by western blot. Cytokine release was evaluated by ELISA.
Key results:
In the concentration range 10-
10–10-
6 M, SP stimulated PPAR- protein expression in monocytes and MDMs, being more effective in cells from healthy smokers. Moreover, in these cells there was a constitutively increased expression of NK1 receptors. SP-induced expression of the PPAR- protein was receptor-mediated, as it was reproduced by the NK1 selective agonist [
Sar9Met(O2)11]
SP and reversed by the competitive NK1 antagonist GR71251. SP-induced maximal effects were similar to those evoked by 15-deoxy-
12,14-prostaglandin J2; an endogenous PPAR- agonist, and were significantly reduced by a PPAR- antagonist. NK1 and PPAR- agonists exerted opposite effects on TNF-
release from monocytes and MDMs.
Conclusions and implications:
Enhancement of PPAR- protein expression represents a novel activity for SP, which could contribute to a range of chronic inflammatory disorders.
Keywords:
substance P, PPAR-, monocytes, macrophages, NK1 receptors, GR 71251, PGJ2, TNF-, tobacco smoke
Abbreviations:
GR71251, [
D-Pro9,(spiro--lactam)Leu10,Trp11]
substance P; GW9662, 2-chloro-5-nitrobenzanilide; MDM, monocyte-derived macrophage; 15d-PGJ2, 15-deoxy-12,14-prostaglandin J2; PPAR-, peroxisome proliferator-activated receptor-; SP, Substance P
