title: Cell-mediated reduction of human β-defensin 1: a major role for mucosal thioredoxin.
abstract: 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.
authors.affiliation: 1] Department of Internal Medicine I, Robert Bosch Hospital, Stuttgart, Germany [2] Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tübingen, Tübingen, Germany.
authors.forename: S U
authors.initials: SU
authors.lastname: Jaeger
authors.forename: B O
authors.initials: BO
authors.lastname: Schroeder
authors.forename: U
authors.initials: U
authors.lastname: Meyer-Hoffert
authors.forename: L
authors.initials: L
authors.lastname: Courth
authors.forename: S N
authors.initials: SN
authors.lastname: Fehr
authors.forename: M
authors.initials: M
authors.lastname: Gersemann
authors.forename: E F
authors.initials: EF
authors.lastname: Stange
authors.forename: J
authors.initials: J
authors.lastname: Wehkamp
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000378:metabolism*; D001310:Auranofin / Q000494:pharmacology; D012634:Bodily Secretions / Q000187:drug effects; D018938:Caco-2 Cells; D002450:Cell Communication; D060833:Cellular Microenvironment; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000235:genetics; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D013879:Thioredoxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; C406407:DEFB1 protein, human; D034741:RNA, Small Interfering; D023083:beta-Defensins; D001310:Auranofin; D013879:Thioredoxins