Cell-mediated reduction of human β-defensin 1: a major role for mucosal thioredoxin.
Cell-mediated reduction of human β-defensin 1: a major role for mucosal thioredoxin.
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人β-防御素1（human β-defensin 1，hBD-1）是由上皮细胞和造血细胞表达的一种抗菌肽。我们最近证明，hBD-1只有在其二硫键被硫氧还蛋白（TRX）或还原环境还原后才显示出抗肠道真菌和念珠菌的活性。在这里，我们表明，除了TRX，谷氧还蛋白（GRX）也能够减少hBD-1，虽然效果要小得多。此外，活的肠和淋巴细胞可以有效地催化细胞外hBD-1的还原。通过对TRX系统的化学抑制或TRX的特异性敲低，我们证明了细胞介导的还原在很大程度上依赖于TRX。在健康对照和炎症性肠病患者的肠组织中的定量PCR揭示了一些（尽管不是全部）氧化还原酶的表达改变，特别是在溃疡性结肠炎中。减少hBD-1和TRX定位于细胞外结肠粘液，表明分泌或膜结合的TRX在体内将hBD-1转化为有效的抗微生物肽。
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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