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人肠道上皮细胞分泌白细胞介素-1受体拮抗剂和白细胞介素-8,但不分泌白细胞介素-1或白细胞介素-6。

Human intestinal epithelial cells secrete interleukin-1 receptor antagonist and interleukin-8 but not interleukin-1 or interleukin-6.

作者信息

Daig R, Rogler G, Aschenbrenner E, Vogl D, Falk W, Gross V, Schölmerich J, Andus T

机构信息

Department of Internal Medicine I, University of Regensburg, Germany.

出版信息

Gut. 2000 Mar;46(3):350-8. doi: 10.1136/gut.46.3.350.

Abstract

BACKGROUND

There is growing evidence that intestinal epithelial cells (IECs) are involved in the mucosal immune system.

AIM

To assess the pattern of cytokines secreted by IECs and lamina propria mononuclear cells (LPMNCs). To achieve this, the expression and secretion of interleukin (IL)-1, IL-1 receptor antagonist (IL-1ra), IL-6, and IL-8 in human primary colonic and ileal IECs and LPMNCs from the same patient were studied.

METHODS

IECs and LPMNCs were isolated from surgical specimens or endoscopic biopsy samples. mRNA expression was investigated by northern blot analysis. Secretion of IL-1beta, IL-6, IL-8, and IL-1ra was measured by enzyme linked immunosorbent assay.

RESULTS

IL-1ra mRNA levels were higher in IECs than in LPMNCs in all probands. IL-8 mRNA was only present in low amounts in the IECs from two controls. In none of the specimens were IL-1beta and IL-6 mRNA present in IECs. Transcripts encoding IL-1beta, IL-1ra, IL-6, and IL-8 were identified in LPMNC preparations of all specimens. IECs from normal mucosa produced no detectable amounts of IL-1beta or IL-6, whereas LPMNCs did. IECs secreted some IL-8 (65 (9) pg/10(5) cells) but significantly more was generated by LPMNCs (408 (43) pg/10(5) cells, p<0.0001). However, IECs secreted more IL-1ra than did LPMNCs (120 (12) v 94 (11) pg/10(5) cells). In acute inflammation, IEC IL-1ra secretion was significantly increased. A correlation between secreted IL-1ra and the macroscopical degree of inflammation was found in Crohn's disease (r = 0.64, p<0.0001, n = 36) and ulcerative colitis (r = 0. 76, p<0.0001, n = 24).

CONCLUSIONS

IECs from normal mucosa express and secrete IL-1ra and low amounts of IL-8, but no IL-1 or IL-6. In inflamed mucosa the secretion of IL-1ra by IECs is slightly increased but may be not sufficient to antagonise the greatly increased production of proinflammatory cytokines by LPMNCs and the IECs themselves.

摘要

背景

越来越多的证据表明肠上皮细胞(IECs)参与黏膜免疫系统。

目的

评估IECs和固有层单核细胞(LPMNCs)分泌细胞因子的模式。为实现这一目的,研究了同一患者的人原发性结肠和回肠IECs及LPMNCs中白细胞介素(IL)-1、IL-1受体拮抗剂(IL-1ra)、IL-6和IL-8的表达及分泌情况。

方法

从手术标本或内镜活检样本中分离IECs和LPMNCs。通过Northern印迹分析研究mRNA表达。采用酶联免疫吸附测定法检测IL-1β、IL-6、IL-8和IL-1ra的分泌。

结果

在所有先证者中,IECs中IL-1ra mRNA水平高于LPMNCs。仅在两名对照者的IECs中少量存在IL-8 mRNA。在IECs中均未检测到IL-1β和IL-6 mRNA。在所有标本的LPMNC制剂中均鉴定出编码IL-1β、IL-1ra、IL-6和IL-8的转录本。正常黏膜的IECs未产生可检测量的IL-1β或IL-6,而LPMNCs可产生。IECs分泌一些IL-8(65(9)pg/10⁵细胞),但LPMNCs产生的IL-8明显更多(408(43)pg/10⁵细胞,p<0.0001)。然而,IECs分泌的IL-1ra比LPMNCs多(120(12)对94(11)pg/10⁵细胞)。在急性炎症中,IECs的IL-1ra分泌显著增加。在克罗恩病(r = 0.64,p<0.0001,n = 36)和溃疡性结肠炎(r = 0.76,p<0.0001,n = 24)中,发现分泌的IL-1ra与炎症的宏观程度之间存在相关性。

结论

正常黏膜的IECs表达并分泌IL-1ra和少量IL-8,但不分泌IL-1或IL-6。在炎症黏膜中,IECs的IL-1ra分泌略有增加,但可能不足以拮抗LPMNCs和IECs自身产生的大量促炎细胞因子。

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