Cytokine profiles differ in newly recruited and resident subsets of mucosal macrophages from inflammatory bowel disease
Cytokine profiles differ in newly recruited and resident subsets of mucosal macrophages from inflammatory bowel disease
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DOI：
10.1016/s0016-5085(97)70030-1
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发表时间：
1997-05-01
期刊：
影响因子：
29.4
通讯作者：
Scott, H
中科院分区：
文献类型：
--
作者：
Rugtveit, J;Nilsen, EM;Scott, H
背景和目标：正常肠粘膜中的大多数巨噬细胞具有成熟的表型，在炎症性肠病（IBD）中，单核细胞样亚群（CD 14（+）L1（+））积累，本研究的目的是表征其在细胞因子方面的潜力。粘附分离固有层单核细胞，去除或不去除CD 14（+）细胞，并通过生物测定研究细胞因子的产生，结果：肿瘤坏死因子-α（TNF-α）、白细胞介素1 β（IL-1 β）和IL-1受体拮抗剂主要存在于髓单核细胞L1阳性的细胞中。在未耗尽的IBD培养物中，TNF-α、IL-1 α和β以及IL-10通过美洲商陆有丝分裂原刺激而显著上调; IL-1 α和β以及IL-10也通过干扰素γ和脂多糖的组合刺激而上调，后者的刺激对正常对照或CD 14-耗尽的IBD培养物没有影响，吲哚美辛引起TNF-α的显著增加，特别是在未耗尽的IBD培养物中，而IL-10和IL-4降低了CD 14（+）和CD 14巨噬细胞中的TNF-α和IL-1 β。结论：在IBD粘膜中，具有单核细胞样表型的巨噬细胞被引发产生TNF-α; IL-1 α和β因此可能具有显著的致病重要性。然而，该CD 14（+）亚群以及粘膜驻留巨噬细胞保留了对几种下调因子如巨噬细胞灭活剂IL-10和IL-4的反应性。
Background & Aims: Most macrophages in the normal intestinal mucosa have a mature phenotype, in inflammatory bowel disease (IBD), a monocyte-like subset (CD14(+)L1(+)) accumulates, The aim of this study was to characterize its potential with regard to cytokines, Methods: Lamina propria mononuclear cells were adherence-separated, with or without depletion of CD14(+) cells, and production of cytokines was investigated by bioassay, enzyme-linked immunosorbent assay, or immunocytochemistry, Results: Tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and IL-1 receptor antagonist were found mainly in cells positive for myelomonocytic L1. In undepleted IBD cultures, TNF-alpha, IL-1 alpha and beta, and IL-10 were markedly up-regulated by pokeweed mitogen stimulation; IL-1 alpha and beta and IL-10 were also up-regulated by stimulation of interferon gamma and lipopolysaccharide in combination, The latter stimulation had no effect on normal control or CD14-depleted IBD cultures, Indomethacin caused a marked increase of TNF-alpha, particularly in undepleted IBD cultures, whereas IL-10 and IL-4 decreased TNF-alpha and IL-1 beta in both CD14(+) and CD14 macrophages. Conclusions: In IBD mucosa, macrophages with a monocyte-like phenotype are primed for production of TNF-alpha; IL-1 alpha and beta may therefore have significant pathogenic importance. However, this CD14(+) subset, as well as the mucosal resident macrophages, have preserved responsiveness to several down-regulatory factors such as the macrophage deactivators IL-10 and IL-4.