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Regulation of Chemokine Function: The Roles of GAG-Binding and Post-Translational Nitration

Applied Immunobiology and Transplantation Group, Institute of Cellular Medicine, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK
Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2017, 18(8), 1692;
Received: 14 June 2017 / Revised: 28 July 2017 / Accepted: 30 July 2017 / Published: 3 August 2017
(This article belongs to the Special Issue Regulation of Chemokine-Receptor Interactions and Functions)
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. View Full-Text
Keywords: chemokine-GAG interaction; synthetic peptide chemistry; PTM; chemokine nitration chemokine-GAG interaction; synthetic peptide chemistry; PTM; chemokine nitration
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Thompson, S.; Martínez-Burgo, B.; Sepuru, K.M.; Rajarathnam, K.; Kirby, J.A.; Sheerin, N.S.; Ali, S. Regulation of Chemokine Function: The Roles of GAG-Binding and Post-Translational Nitration. Int. J. Mol. Sci. 2017, 18, 1692.

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