Interleukin-4 induces a switch of human intestinal mast cells from proinflammatory cells to Th2-type cells

Interleukin-4 induces a switch of human intestinal mast cells from proinflammatory cells to Th2-type cells
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DOI:
10.1159/000053695
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发表时间:
2001-01-01
影响因子:
2.8
通讯作者:
Lorentz, A
Lorentz, A
中科院分区:
医学3区
文献类型:
--
作者:
Bischoff, SC;Sellge, G;Lorentz, A

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背景:近年来,肥大细胞被认为是多种细胞因子的有效细胞来源。然而,鲜为人知的是,来自粘膜部位的成熟的人肥大细胞的细胞因子的产生的调节。研究方法:从肠粘膜中分离人肥大细胞,并在干细胞因子(SCF)单独或与IL-4组合存在下培养14天。然后通过IgE受体交联或细菌感染刺激肥大细胞,并通过RT-PCR和ELISA检测细胞因子的产生。结果如下:我们发现人肠道肥大细胞在没有进一步刺激的情况下产生促炎细胞因子如TNF-α、IL-1 β和IL-6。用革兰氏阴性细菌(大肠杆菌等)刺激细胞引起TNF-α表达的上调。在IgE受体交联后,我们发现了Th 2细胞因子IL-3、IL-5和IL-13的额外表达。有趣的是,IL-3、IL-5和IL-13的mRNA也在未刺激的肥大细胞中表达,只要它们在SCF和IL-4存在下培养。此外,IL-4使肥大细胞能够释放IL-5,以响应细菌的挑战。结论:在肥大细胞存活因子SCF的存在下,成熟的人肥大细胞主要产生促炎细胞因子,而在SCF和IL-4的存在下,肥大细胞不仅产生促炎细胞因子,而且产生Th 2细胞因子。版权所有(C)2001 S. Karger AG,巴塞尔。
Background: During the last years, mast cells have been recognized as a potent cellular source of multiple cytokines. However, little is known about the regulation of cytokine production by mature human mast cells derived from mucosal sites. Methods: Human mast cells were isolated from intestinal mucosa and cultured for 14 days in the presence of stem cell factor (SCF) alone or in combination with IL-4. Mast cells were then stimulated by IgE receptor cross-linking or bacterial infection and cytokine production was examined by RT-PCR and ELISA. Results: We found that hu man intestinal mast cells produce proinflammatory cytokines such as TNF-alpha, IL-1 beta and IL-6 without further stimulation. Stimulation of the cells with gram-negative bacteria (Escherichia coli and others) caused an upregulation of TNF-a expression. Following IgE receptor cross-linking, we found additional expression of the Th2 cytokines IL-3, IL-5 and IL-13. Interestingly, mRNA for IL-3, IL-5 and IL-13 was also expressed in unstimulated mast cells provided they were cultured in the presence of SCF and IL-4. Moreover, IL-4 rendered mast cells capable of releasing IL-5 in response to bacterial challenge. Conclusion: In the presence of the mast cell survival factor SCF, mature human mast cells produce predominantly proinflammatory cytokines, whereas in the presence of SCF and IL-4, mast cells produce not only proinflammatory but also Th2 cytokines. Copyright (C) 2001 S. Karger AG, Basel.