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Regulation of chemokine function: The roles of GAG-binding and post-translational nitration

Lookup NU author(s): Sarah Thompson, Beatriz Martinez Burgo, Professor John Kirby, Professor Neil Sheerin, Professor Simi Ali

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. The primary function of chemokines is to direct the migration of leukocytes to the site of injury during inflammation. The effects of chemokines are modulated by several means, including binding to G-protein coupled receptors (GPCRs), binding to glycosaminoglycans (GAGs), and through post-translational modifications (PTMs). GAGs, present on cell surfaces, bind chemokines released in response to injury. Chemokines bind leukocytes via their GPCRs, which directs migration and contributes to local inflammation. Studies have shown that GAGs or GAG-binding peptides can be used to interfere with chemokine binding and reduce leukocyte recruitment. Post-translational modifications of chemokines, such as nitration, which occurs due to the production of reactive species during oxidative stress, can also alter their biological activity. This review describes the regulation of chemokine function by GAG-binding ability and by post-translational nitration. These are both aspects of chemokine biology that could be targeted if the therapeutic potential of chemokines, like CXCL8, to modulate inflammation is to be realised.


Publication metadata

Author(s): Thompson S, Martinez-Burgo B, Sepuru KM, Rajarathnam K, Kirby JA, Sheerin NS, Ali S

Publication type: Review

Publication status: Published

Journal: International Journal of Molecular Sciences

Year: 2017

Volume: 18

Issue: 8

Online publication date: 03/08/2017

Acceptance date: 30/07/2017

ISSN (print): 1661-6596

ISSN (electronic): 1422-0067

Publisher: MDPI AG

URL: https://doi.org/10.3390/ijms18081692

DOI: 10.3390/ijms18081692


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