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Truncated and Full-Length Thioredoxin-1 Have Opposing Activating and Inhibitory Properties for Human Complement with Relevance to Endothelial Surfaces.

Author:
  • Ben King
  • Justyna Nowakowska
  • Christian M Karsten
  • Jörg Köhl
  • Erik Renström
  • Anna Blom
Publishing year: 2012
Language: English
Pages: 4103-4112
Publication/Series: Journal of immunology (Baltimore, Md. : 1950)
Volume: 188
Issue: 8
Document type: Journal article
Publisher: American Association of Immunologists

Abstract english

Thioredoxin (Trx)-1 is a small, ubiquitously expressed redox-active protein with known important cytosolic functions. However, Trx1 is also upregulated in response to various stress stimuli, is found both at the cell surface and secreted into plasma, and has known anti-inflammatory and antiapoptotic properties. Previous animal studies have demonstrated that exogenous Trx1 delivery can have therapeutic effects in a number of disease models and have implicated an interaction of Trx1 with the complement system. We found that Trx1 is expressed in a redox-active form at the surface of HUVEC and acts as an inhibitor of complement deposition in a manner dependent on its Cys-Gly-Pro-Cys active site. Inhibition occurred at the point of the C5 convertase of complement, regulating production of C5a and the membrane attack complex. A truncated form of Trx1 also exists in vivo, Trx80, which has separate nonoverlapping functions compared with the full-length Trx1. We found that Trx80 activates the classical and alternative pathways of complement activation, leading to C5a production, but the inflammatory potential of this was also limited by the binding of inhibitors C4b-binding protein and factor H. This study adds a further role to the known anti-inflammatory properties of Trx1 and highlights the difference in function between the full-length and truncated forms.

Keywords

  • Immunology in the medical area

Other

Published
  • Protein Chemistry, Malmö
  • Islet patophysiology
  • ISSN: 1550-6606
Erik Renström
E-mail: erik.renstrom [at] med.lu.se

Deputy head of department

Department of Clinical Sciences, Malmö

+46 40 39 11 57

+46 40 39 11 57

Principal investigator

Islet patophysiology

+46 40 39 11 57

+46 40 39 11 57

20-3-308

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