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

King, Ben LU ; Nowakowska, Justyna; Karsten, Christian M; Köhl, Jörg; Renström, Erik LU and Blom, Anna LU (2012) In Journal of immunology (Baltimore, Md. : 1950) 188(8). p.4103-4112
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of immunology (Baltimore, Md. : 1950)
volume
188
issue
8
pages
4103 - 4112
publisher
American Association of Immunologists
external identifiers
  • WOS:000302641400058
  • PMID:22430737
  • Scopus:84860320635
ISSN
1550-6606
DOI
10.4049/jimmunol.1101295
language
English
LU publication?
yes
id
1a0adb92-f11f-4bed-9446-b8aca9217c0f (old id 2431620)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22430737?dopt=Abstract
date added to LUP
2012-04-03 12:31:57
date last changed
2016-11-01 10:16:40
@misc{1a0adb92-f11f-4bed-9446-b8aca9217c0f,
  abstract     = {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.},
  author       = {King, Ben and Nowakowska, Justyna and Karsten, Christian M and Köhl, Jörg and Renström, Erik and Blom, Anna},
  issn         = {1550-6606},
  language     = {eng},
  number       = {8},
  pages        = {4103--4112},
  publisher    = {ARRAY(0xc63e740)},
  series       = {Journal of immunology (Baltimore, Md. : 1950)},
  title        = {Truncated and Full-Length Thioredoxin-1 Have Opposing Activating and Inhibitory Properties for Human Complement with Relevance to Endothelial Surfaces.},
  url          = {http://dx.doi.org/10.4049/jimmunol.1101295},
  volume       = {188},
  year         = {2012},
}