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Review ArticleReview Article

CC Chemokine Receptors and Chronic Inflammation—Therapeutic Opportunities and Pharmacological Challenges

Gemma E. White, Asif J. Iqbal and David R. Greaves
Christopher J. Garland, ASSOCIATE EDITOR
Pharmacological Reviews January 2013, 65 (1) 47-89; DOI: https://doi.org/10.1124/pr.111.005074
Gemma E. White
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
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Asif J. Iqbal
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
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David R. Greaves
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
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Christopher J. Garland
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
Roles: ASSOCIATE EDITOR
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Abstract

Chemokines are a family of low molecular weight proteins with an essential role in leukocyte trafficking during both homeostasis and inflammation. The CC class of chemokines consists of at least 28 members (CCL1-28) that signal through 10 known chemokine receptors (CCR1-10). CC chemokine receptors are expressed predominantly by T cells and monocyte-macrophages, cell types associated predominantly with chronic inflammation occurring over weeks or years. Chronic inflammatory diseases including rheumatoid arthritis, atherosclerosis, and metabolic syndrome are characterized by continued leukocyte infiltration into the inflammatory site, driven in large part by excessive chemokine production. Over years or decades, persistent inflammation may lead to loss of tissue architecture and function, causing severe disability or, in the case of atherosclerosis, fatal outcomes such as myocardial infarction or stroke. Despite the existence of several clinical strategies for targeting chronic inflammation, these diseases remain significant causes of morbidity and mortality globally, with a concomitant economic impact. Thus, the development of novel therapeutic agents for the treatment of chronic inflammatory disease continues to be a priority. In this review we introduce CC chemokine receptors as critical mediators of chronic inflammatory responses and explore their potential role as pharmacological targets. We discuss functions of individual CC chemokine receptors based on in vitro pharmacological data as well as transgenic animal studies. Focusing on three key forms of chronic inflammation—rheumatoid arthritis, atherosclerosis, and metabolic syndrome—we describe the pathologic function of CC chemokine receptors and their possible relevance as therapeutic targets.

Footnotes

  • The work in the Greaves laboratory is funded by the British Heart Foundation, Programme Grant Number RG/10/15/28578. G.E.W. is funded by British Heart Foundation project Grant Number PG/10/60/28496.

  • dx.doi.org/10.1124/pr.111.005074.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 65 (1)
Pharmacological Reviews
Vol. 65, Issue 1
1 Jan 2013
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Review ArticleReview Article

CC Chemokine Receptors in Inflammation

Gemma E. White, Asif J. Iqbal and David R. Greaves
Pharmacological Reviews January 1, 2013, 65 (1) 47-89; DOI: https://doi.org/10.1124/pr.111.005074

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Review ArticleReview Article

CC Chemokine Receptors in Inflammation

Gemma E. White, Asif J. Iqbal and David R. Greaves
Pharmacological Reviews January 1, 2013, 65 (1) 47-89; DOI: https://doi.org/10.1124/pr.111.005074
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  • Article
    • Abstract
    • I. Introduction
    • II. CC Chemokine Receptors
    • III. Role of Chemokines in Chronic Inflammatory Diseases
    • IV. Chemokine Receptor Drugs in Clinical Trials
    • V. Critical Assessment of Chemokine Receptors as Anti-inflammatory Drug Targets
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