Attenuated induction of epithelial and leukocyte serine antiproteases elafin and secretory leukocyte protease inhibitor in Crohn's disease
Attenuated induction of epithelial and leukocyte serine antiproteases elafin and secretory leukocyte protease inhibitor in Crohn's disease
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DOI：
10.1189/jlb.0906581
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发表时间：
2007-04-01
影响因子：
5.5
通讯作者：
Wehkamp, Jan
中科院分区：
文献类型：
--
作者：
Schmid, Michael;Fellermann, Klaus;Wehkamp, Jan
Elafin（或皮肤源性抗白细胞蛋白酶）和分泌性白细胞蛋白酶抑制剂（SLPI）是丝氨酸抗蛋白酶，可拮抗人中性粒细胞弹性酶（HNE），从而防止炎症细胞过度释放蛋白水解酶造成组织损伤。此外，elafin和SLPI是具有广泛抗菌活性的“防御素样”分子。蛋白酶和拮抗剂之间的平衡至关重要地决定了克罗恩病（CD）和溃疡性结肠炎（UC）的炎症过程。采用real - tix PCR定量分析117例患者（47例CD， 45例UC， 25例对照）340例活检组织的结肠、促炎细胞因子IL-8、蛋白酶（HNE）和抗蛋白酶mRNA （elafin和SLPI）。对51个结肠石蜡切片（CD切片23个，UC切片11个，对照组17个）进行组织学炎症评分，免疫染色对HNE、elafin和SLPI进行定位和半定量。UC和CD的促炎IL-8、组织学炎症程度和粒细胞含量相似。Elafin主要染色于上皮，SLPI主要染色于粘膜炎症细胞。两种炎症性肠病的HNE mRNA水平和免疫染色均升高。与非炎症UC相比，炎症UC的mRNA水平和抗蛋白酶elafin和SLPI的免疫染色明显增强。令人惊讶的是，将炎症性CD与非炎症性CD进行比较，elafin的这种增加明显不那么明显，甚至SLPI也没有。尽管炎症程度和蛋白酶水平相当，但两种抗蛋白酶的诱导作用在CD中都减弱了。这可能有助于CD中组织破坏的跨壁深度。Elafin和SLPI可能被添加到防御素样肽的列表中，在CD和UC中诱导作用减弱。
Elafin (or skin-derived antileukoprotease) and secretory leukocyte protease inhibitor (SLPI) are serine antiproteases antagonizing human neutrophil elastase (HNE), thereby preventing tissue injury from excessive release of proteolytic enzymes by inflammatory cells. Furthermore, elafin and SLPI are "defensin-like" molecules with broad antimicrobial activity. The balance between proteases and antagonists tray critically determine inflammatory processes in Crohn's disease (CD) and ulcerative colitis (UC). Real-tithe PCR was performed to quantitate colonic, proinflammatory cytokine IL-8, protease (HNE), and antiprotease mRNA (elafin and SLPI) in a total of 340 biopsies from 117 patients (47 CD, 45 UC, 25 controls). Histological inflammation was scored, and HNE, elafin, and SLPI were localized and semiquantified by immunostaining in 51 colonic paraffin sections (23 CD, 11 UC, 17 controls). Proinflammatory IL-8, degree of histological inflammation, and granulocyte content were similar in UC and CD. Elafin stained predominantly in the epithelium and SLPI in mucosal inflammatory cells. HNE mRNA levels and immunostaining were increased equally in both forms of inflammatory bowel disease. Levels of mRNA and immunostaining of the antiproteases elafin and SLPI were enhanced strongly in inflamed versus noninflamed UC. It is surprising that comparing inflamed versus noninflamed CD, this increase was significantly less pronounced for elafin and even lacking for SLPI. Despite comparable degrees of inflammation and protease levels, the induction of both antiproteases was attenuated in CD. This could contribute to the transmural depth of tissue destruction in CD. Elafin and SLPI may be added to the list of defensin-like peptides with diminished induction in CD versus UC.