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
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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2431620
- author
- King, Ben
LU
; Nowakowska, Justyna
; Karsten, Christian M
; Köhl, Jörg
; Renström, Erik
LU
and Blom, Anna
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of immunology
- 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
- 2016-04-04 09:09:21
- date last changed
- 2022-04-23 19:14:19
@article{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 = {{American Association of Immunologists}},
series = {{Journal of immunology}},
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}},
doi = {{10.4049/jimmunol.1101295}},
volume = {{188}},
year = {{2012}},
}