Toggle Main Menu Toggle Search

Open Access padlockePrints

Using evasins to target the chemokine network in inflammation

Lookup NU author(s): Professor Akane Kawamura



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Inflammation, is driven by a network comprising cytokines, chemokines, their target receptors and leukocytes, and is a major pathologic mechanism that adversely affects organ function in diverse human diseases. Despite being supported by substantial target validation, no successful anti-chemokine therapeutic to treat inflammatory disease has yet been developed. This is in part because of the robustness of the chemokine network, which emerges from a large total chemokine load in disease, promiscuous expression of receptors on leukocytes, promiscuous and synergistic interactions between chemokines and receptors, and feedforward loops created by secretion of chemokines by leukocytes themselves. Many parasites, including viruses, helminths and ticks, evade the chemokine network by producing proteins that bind promiscuously to chemokines or their receptors. Evasins - three small glycoproteins identified in the saliva of the brown dog tick - bind multiple chemokines, and are active in several animal models of inflammatory disease. Over 50 evasin homologs have recently been identified from diverse tick species. Characterization of the chemokine binding patterns of evasins show that several have anti-chemokine activities that extend substantially beyond those previously described. These studies indicate that evasins function at the site of the tick bite by reducing total chemokine load. This not only reduces chemokine signaling to receptors, but also interrupts feedforward loops, thus disabling the chemokine network. Taking the lead from nature, a goal for the development of new anti-chemokine therapeutics would be to reduce the total chemokine load in disease. This could be achieved by administering appropriate evasin combinations or by smaller peptides that mimic evasin action.

Publication metadata

Author(s): Bhattacharya S, Kawamura A

Publication type: Book Chapter

Publication status: Published

Book Title: Advances in Protein Chemistry and Structural Biology – Inflammatory Diseases – Part A

Year: 2020

Volume: 119

Pages: 1-38

Print publication date: 24/01/2020

Online publication date: 26/11/2019

Acceptance date: 30/08/2019

Publisher: Elsevier


DOI: 10.1016/bs.apcsb.2019.09.003

Library holdings: Search Newcastle University Library for this item

ISBN: 18761623