Post-translational control of chemokines: a role for decoy receptors?
ABSTRACT It is well-established that chemokines play a critical role in the orchestration of inflammation and immunity. Interactions between chemokines and their receptors are essential for the homing of specific subsets of leukocytes to their functional microenvironments. They also influence other diverse biological processes such as development, leukocyte activation, Th1/Th2 polarisation, tumour metastasis, angiogenesis, and HIV pathogenesis. However, despite their importance, only now are we beginning to understand the complex regulation brought to bear on these molecules. In this review, we discuss a number of these key chemokine regulators that exert their influence once these proteins have been synthesised. We examine (i) chemokine storage, release, and presentation, (ii) protease regulation, (iii) viral manipulation of host chemokines, and (iv) natural mammalian receptor antagonists. Principally, the growing evidence for a role for decoy receptors in the chemokine system is discussed. In particular, the potential decoy function of the 'silent' pro-inflammatory chemokine receptor D6 is described alongside two other candidate decoy receptor molecules, DARC, and CCX-CKR. Dissecting the biological and pathological function of these chemokine controllers will lead to a deeper understanding of chemokine regulation, and may reveal novel strategies to therapeutically modify the chemokine system.
- SourceAvailable from: Manel Juan Otero
Chapter: Chemokines and Chemokine Receptors[Show abstract] [Hide abstract]
ABSTRACT: There is a structural and a functional classification of chemokines. The former includes four groups: CXC, CC, C and CX3C chemokines. There is a redundancy and binding promiscuity between chemokine receptors and their ligands. Recently, a functional classification distinguishing between inflammatory and homeostatic chemokines has been introduced. However, numerous effects of these chemokines overlap. For example, numerous homeostatic chemokines, which are involved in lymphocyte recruitment and lymphoid tissue organization, may also play a role in B cell migration underlying germinal center formation within the inflamed synovium. Anti-chemokine and anti-chemokine receptor targeting may be therapeutically used in future biological therapy of arthritis. In addition to the clear clinical benefit, we can learn a lot from these trials about the actions of the targeted chemokines and their receptors. Today, most data in this field are obtained from experimental models of arthritis; however, results of some human trials have also become available. Thus, it is possible that a number of specific chemokine and chemokine receptor antagonists will be administered to arthritis patients in the near future. Hopefully, some of these potential treatment modalities will be used to control inflammation, prevent joint destruction and thus will benefit our patients.eLS, 12/2009; , ISBN: 9780470015902
Article: 7TM Receptors.[Show abstract] [Hide abstract]
ABSTRACT: ALEXANDER, S.P.H., MATHIE, A. & PETERS, J.A. (2007). Guide to Receptors and Channels (GRAC), 2nd edition (2007 revision). Br. J. Pharmacol., 150 (Suppl. 1), S1–S168.British Journal of Pharmacology 03/2007; 150 Suppl 1:S4-S81. DOI:10.1038/sj.bjp.0707202 · 4.99 Impact Factor