Interleukin-4 and dexamethasone counterregulate extracellular matrix remodelling and phagocytosis in type-2 macrophages
Interleukin-4 and dexamethasone counterregulate extracellular matrix remodelling and phagocytosis in type-2 macrophages
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DOI：
10.1111/j.0300-9475.2005.01524.x
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发表时间：
2005-01-01
影响因子：
3.7
通讯作者：
Goerdt, S
中科院分区：
文献类型：
--
作者：
Gratchev, A;Kzhyshkowska, J;Goerdt, S
选择性活化巨噬细胞（Mphi2）是由Th2细胞因子和糖皮质激素（GC）诱导的，根据其抗炎特性可以与经典活化效应巨噬细胞（Mphi1）区分开来。此外，Mphi2参与Th2/Th1扭曲，增强抗原摄取和加工，支持组织重塑和愈合。为了系统地阐明Mphi2群体的异质性，我们分析了白细胞介素-4 （IL-4）或GC产生的Mphi2群体中涉及细胞外基质（ECM）重塑、炎症和吞噬的一些基因。利用实时聚合酶链反应，我们证明了ECM成分tenascin-C被IL-4刺激，而它被地塞米松抑制。ECM重构酶- MMP-1和MMP-12 -和组织转谷氨酰胺酶（TG）表现出类似的调节模式。FXIIIa是另一种推测与mphi2相关的TG，受IL-4和GC的协同调节。酶联免疫吸附分析显示，IL-4可诱导mphi2相关趋化因子AMAC-1、MCP-4或TARC的产生，并可通过GC调节。GC刺激了调理化和非调理化颗粒的吞噬，而IL-4仅具有调节作用，其部分原因可能是GC强烈而选择性地诱导了非调理化颗粒的清除受体hMARCO的表达模式。综上所述，IL-4和GC刺激Mphi可拮抗ECM重塑相关分子的表达以及调理和非调理颗粒的吞噬作用。
Alternatively activated macrophages (Mphi2) are induced by Th2 cytokines and by glucocorticoids (GC), and can be distinguished from classically activated effector macrophages (Mphi1) on the basis of their anti-inflammatory properties. In addition, Mphi2 are involved in Th2/Th1 skewing, enhance antigen uptake and processing and support tissue remodelling and healing. In order to elucidate the heterogeneity of Mphi2 population systematically, we analysed a number of genes involved in extracellular matrix (ECM) remodelling, inflammation and phagocytosis in Mphi2 populations generated with interleukin-4 (IL-4) or GC. Using real-time polymerase chain reaction, we demonstrated that the ECM component, tenascin-C, is stimulated by IL-4, whereas it is suppressed by dexamethasone. The ECM remodelling enzymes - MMP-1 and MMP-12 - and tissue transglutaminase (TG) showed a similar regulation pattern. FXIIIa, another putative Mphi2-associated TG, was synergistically regulated by IL-4 and GC. Enzyme-linked immunosorbent assay analysis revealed that the production of Mphi2-associated chemokines, AMAC-1, MCP-4 or TARC, was induced by IL-4 and was modulated by GC. Phagocytosis of opsonized and non-opsonized particles was stimulated by GC, whereas IL-4 had only a modulatory effect, what may be partially explained by the expression pattern of hMARCO, a scavenger receptor for non-opsonized particles, that was strongly and selectively induced by GC. In conclusion, stimulation of Mphi with IL-4 and GC regulate antagonistically the expression of ECM remodelling-related molecules and phagocytosis of opsonized and non-opsonized particles.