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Cell-mediated reduction of human β-defensin 1: a major role for mucosal thioredoxin

Human β-defensin 1 (hBD-1) is an antimicrobial peptide expressed by epithelia and hematopoietic cells. We demonstrated recently that hBD-1 shows activity against enteric commensals and Candida species only after its disulfide bonds have been reduced by thioredoxin (TRX) or a reducing environment. He...

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Autores principales: Jaeger, S U, Schroeder, B O, Meyer-Hoffert, U, Courth, L, Fehr, S N, Gersemann, M, Stange, E F, Wehkamp, J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3806438/
https://www.ncbi.nlm.nih.gov/pubmed/23571504
http://dx.doi.org/10.1038/mi.2013.17
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author Jaeger, S U
Schroeder, B O
Meyer-Hoffert, U
Courth, L
Fehr, S N
Gersemann, M
Stange, E F
Wehkamp, J
author_facet Jaeger, S U
Schroeder, B O
Meyer-Hoffert, U
Courth, L
Fehr, S N
Gersemann, M
Stange, E F
Wehkamp, J
author_sort Jaeger, S U
collection PubMed
description Human β-defensin 1 (hBD-1) is an antimicrobial peptide expressed by epithelia and hematopoietic cells. We demonstrated recently that hBD-1 shows activity against enteric commensals and Candida species only after its disulfide bonds have been reduced by thioredoxin (TRX) or a reducing environment. Here we show that besides TRX, glutaredoxin (GRX) is also able to reduce hBD-1, although with far less efficacy. Moreover, living intestinal and lymphoid cells can effectively catalyze reduction of extracellular hBD-1. By chemical inhibition of the TRX system or specific knockdown of TRX, we demonstrate that cell-mediated reduction is largely dependent on TRX. Quantitative PCR in intestinal tissues of healthy controls and inflammatory bowel disease patients revealed altered expression of some, although not all, redox enzymes, especially in ulcerative colitis. Reduced hBD-1 and TRX localize to extracellular colonic mucus, suggesting that secreted or membrane-bound TRX converts hBD-1 to a potent antimicrobial peptide in vivo.
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spelling pubmed-38064382013-10-23 Cell-mediated reduction of human β-defensin 1: a major role for mucosal thioredoxin Jaeger, S U Schroeder, B O Meyer-Hoffert, U Courth, L Fehr, S N Gersemann, M Stange, E F Wehkamp, J Mucosal Immunol Article Human β-defensin 1 (hBD-1) is an antimicrobial peptide expressed by epithelia and hematopoietic cells. We demonstrated recently that hBD-1 shows activity against enteric commensals and Candida species only after its disulfide bonds have been reduced by thioredoxin (TRX) or a reducing environment. Here we show that besides TRX, glutaredoxin (GRX) is also able to reduce hBD-1, although with far less efficacy. Moreover, living intestinal and lymphoid cells can effectively catalyze reduction of extracellular hBD-1. By chemical inhibition of the TRX system or specific knockdown of TRX, we demonstrate that cell-mediated reduction is largely dependent on TRX. Quantitative PCR in intestinal tissues of healthy controls and inflammatory bowel disease patients revealed altered expression of some, although not all, redox enzymes, especially in ulcerative colitis. Reduced hBD-1 and TRX localize to extracellular colonic mucus, suggesting that secreted or membrane-bound TRX converts hBD-1 to a potent antimicrobial peptide in vivo. Nature Publishing Group 2013-11 2013-04-10 /pmc/articles/PMC3806438/ /pubmed/23571504 http://dx.doi.org/10.1038/mi.2013.17 Text en Copyright © 2013 Society for Mucosal Immunology http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Article
Jaeger, S U
Schroeder, B O
Meyer-Hoffert, U
Courth, L
Fehr, S N
Gersemann, M
Stange, E F
Wehkamp, J
Cell-mediated reduction of human β-defensin 1: a major role for mucosal thioredoxin
title Cell-mediated reduction of human β-defensin 1: a major role for mucosal thioredoxin
title_full Cell-mediated reduction of human β-defensin 1: a major role for mucosal thioredoxin
title_fullStr Cell-mediated reduction of human β-defensin 1: a major role for mucosal thioredoxin
title_full_unstemmed Cell-mediated reduction of human β-defensin 1: a major role for mucosal thioredoxin
title_short Cell-mediated reduction of human β-defensin 1: a major role for mucosal thioredoxin
title_sort cell-mediated reduction of human β-defensin 1: a major role for mucosal thioredoxin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3806438/
https://www.ncbi.nlm.nih.gov/pubmed/23571504
http://dx.doi.org/10.1038/mi.2013.17
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