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Effective suppression of C5a-induced proinflammatory response using anti-human C5a repebody

Title
Effective suppression of C5a-induced proinflammatory response using anti-human C5a repebody
Author
양철수
Keywords
Repebody; C5a; Inflammatory disease; Modular engineering
Issue Date
2016-09
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v. 477, NO. 4, Page. 1072-1077
Abstract
The strongest anaphylatoxin, C5a, plays a critical role in the proinflammatory responses, causing the pathogenesis of a number of inflammatory diseases including sepsis, asthma, and rheumatoid arthritis. Inhibitors of C5a thus have great potential as therapeutics for various inflammatory disorders. Herein, we present the development of a high-affinity repebody against human C5a (hC5a), which effectively suppresses the proinflammatory response. A repebody scaffold composed of leucine-rich repeat (LRR) modules was previously developed as an alternative protein scaffold. A repebody specifically binding to hC5a was selected through a phage display, and its affinity was increased up to 5 nM using modular engineering. The repebody was shown to effectively inhibit the production of C5a-induced proinflammatory cytokines by human monocytes. To obtain insight into a mode of action by the repebody, we determined its crystal structure in complex with hC5a. A structural analysis revealed that the repebody binds to the D1 and D3 regions of hC5a, overlapping several epitope residues with the hC5a receptor (hC5aR). It is thus likely that the repebody suppresses the hC5a-mediated immune response in monocytes by blocking the binding of hC5a to its receptor. The anti-hC5a repebody can be developed as a potential therapeutic for C5a-involved inflammatory diseases. (C) 2016 Elsevier Inc. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0006291X16311561?via%3Dihubhttp://repository.hanyang.ac.kr/handle/20.500.11754/80432
ISSN
0006-291X; 1090-2104
DOI
10.1016/j.bbrc.2016.07.041
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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