| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
RECEPTORS AND SIGNAL TRANSDUCTION
Department of Pharmacology, National University of Singapore, Singapore
Submitted 12 February 2007 ; accepted in final form 3 May 2007
Neuropeptides play an important role in the active communication between the nervous and immune systems. Substance P (SP) is a prominent neuropeptide involved in neurogenic inflammation and has been reported to exert various proinflammatory actions on inflammatory leukocytes including neutrophils. The present study further investigated the modulatory effect of SP (1 µM) on chemokine production and chemokine receptor expression in primary mouse neutrophils. Our results showed that SP primed neutrophils for chemotactic responses not only to the CXC chemokine macrophage inflammatory protein (MIP)-2/CXCL2 but also to the CC chemokine MIP-1
/CCL3. The activating effect of SP on neutrophils was further evidenced by upregulation of the CD11b integrin, the activation marker of neutrophils. SP induced both the mRNA and protein expression of the chemokines MIP-1/CCL3 and MIP-2/CXCL2 in neutrophils and upregulated the chemokine receptors CC chemokine receptor (CCR)-1 and CXC chemokine receptor (CXCR)-2. This stimulatory effect on chemokine and chemokine receptor expression in neutrophils was further found to be neurokinin-1 receptor (NK-1R) specific. Pretreatment with selective NK-1R antagonists inhibited SP-triggered activation of neutrophils and chemokine and chemokine receptor upregulation. Moreover, SP-induced chemokine upregulation was NF-
B dependent. SP time dependently induced NF-B p65 binding activity, IB degradation, and NF-B p65 nuclear translocation in neutrophils. Inhibition of NF-B activation with its inhibitor Bay11-7082 (10 µM) abolished SP-induced NF-B binding activity and upregulation of MIP-1/CCL3 and MIP-2/CXCL2 in neutrophils. Together, these results suggest that SP exerts a direct stimulatory effect on the expression of chemokines and chemokine receptors in mouse neutrophils. The effect is NK-1R mediated, involving NF-B activation.
chemokines and receptors; neuro-immune interaction; neurokinin-1 receptor; primary leukocytes; NF-B activation
This article has been cited by other articles:
|
|
 |
|
  J. Sun, R. D. Ramnath, R. Tamizhselvi, and M. Bhatia Role of protein kinase C and phosphoinositide 3-kinase-Akt in substance P-induced proinflammatory pathways in mouse macrophages FASEB J, April 1, 2009; 23(4): 997 - 1010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sun, R. D. Ramnath, R. Tamizhselvi, and M. Bhatia Neurokinin A engages neurokinin-1 receptor to induce NF-{kappa}B-dependent gene expression in murine macrophages: implications of ERK1/2 and PI 3-kinase/Akt pathways Am J Physiol Cell Physiol, September 1, 2008; 295(3): C679 - C691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sun, R. D. Ramnath, L. Zhi, R. Tamizhselvi, and M. Bhatia Substance P enhances NF-{kappa}B transactivation and chemokine response in murine macrophages via ERK1/2 and p38 MAPK signaling pathways Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1586 - C1596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. Ng, H. Zhang, A. Hegde, and M. Bhatia Role of preprotachykinin-A gene products on multiple organ injury in LPS-induced endotoxemia J. Leukoc. Biol., February 1, 2008; 83(2): 288 - 295. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
