Targeting of a common receptor shared by CXCL8 and N-Ac-PGP as a therapeutic strategy to alleviate chronic neutrophilic lung diseases.

Abstract

Persistent neutrophilia is implicated in the pathology of several chronic lung diseases and consequently targeting the signals that drive the recruitment of these cells offers a plausible therapeutic strategy. The tripeptide Pro-Gly-Pro (PGP) is a neutrophil chemoattractant derived from extracellular matrix collagen and implicated in diseases such as COPD and cystic fibrosis. It was anticipated that PGP exerts its chemoatactic activity by mimicking key sequences found within classical neutrophil chemokines, such as CXCL8, and binding their receptors, CXCR1/2. Recently, however, the role of CXCR1/2 as the receptors for PGP has been questioned. In this issue of European Journal of Pharmacology, three studies address this controversy and demonstrate CXCR1/2 to be a common receptor for CXCL8 and PGP. Accordingly, these studies demonstrate the therapeutic potential of targeting this shared receptor to simultaneously alleviate neutrophilic inflammation driven by multiple neutrophil chemoattractants.

• Authors: Robert J Snelgrove
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 667 Issue 1-3 Pg. 1-5 (Sep 30 2011) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 21669195 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Interleukin-8
• Oligopeptides
• Receptors, CXCR
• prolyl-glycyl-proline
• Proline

Topics

• Acetylation
• Chronic Disease (drug therapy)
• Humans
• Interleukin-8 (metabolism)
• Lung Diseases (drug therapy, immunology, metabolism)
• Molecular Targeted Therapy (methods)
• Neutrophils (drug effects, metabolism)
• Oligopeptides (metabolism)
• Proline (analogs & derivatives, metabolism)
• Receptors, CXCR (metabolism)