In Vivo and In Vitro Roles of IL-21 in Inflammation1
In Vivo and In Vitro Roles of IL-21 in Inflammation1
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DOI：
10.4049/jimmunol.173.12.7521
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发表时间：
2004-12
期刊：
影响因子：
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通讯作者：
M. Pelletier;A. Bouchard;D. Girard
中科院分区：
文献类型：
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作者：
M. Pelletier;A. Bouchard;D. Girard
IL-21是一种已知通过IL-21 R介导其生物学作用的细胞因子，由特异性链IL-21 R α和共同γ链（CD132）组成。最近的数据表明，IL-21具有促炎特性。然而，没有明确的证据表明IL-21在体内诱导炎症，并且奇怪的是，IL-21和中性粒细胞之间的相互作用从未被研究过，尽管这些细胞表达CD 132并对参与炎性疾病的其他CD 132依赖性细胞因子产生应答。使用小鼠气囊模型，我们发现IL-21基于中性粒细胞和单核细胞群体的募集在体内诱导炎症。与LPS相比，将IL-21施用到气囊中并没有显著增加IL-6、CCL5、CCL3和CXCL2的浓度。我们证明HL-60细胞表达IL-21 R α，在其向中性粒细胞分化的过程中下调，并且在中性粒细胞中未检测到IL-21 R α。与此同时，IL-21诱导HL-60细胞中的Erk-1/2磷酸化，但在中性粒细胞中不诱导。为了排除即使在缺乏IL-21 R α的情况下IL-21也能激活中性粒细胞的可能性，我们证明了IL-21不调节几种中性粒细胞功能。IL-21诱导的Erk-1/2磷酸化与HL-60向中性粒细胞、单核细胞或巨噬细胞的增殖或分化无关。在人单核细胞和单核细胞衍生的巨噬细胞中检测到IL-21 R α，但IL-21仅在单核细胞衍生的巨噬细胞中增加CXCL 8的产生。我们得出结论，IL-21是一种促炎细胞因子，但不是中性粒细胞激动剂。我们认为IL-21通过一种独立于IL-6、CCL3、CCL5和CXCL2产生的机制在体内间接吸引中性粒细胞。
IL-21 is a cytokine known to mediate its biological action via the IL-21R, composed of a specific chain, IL-21Rα, and the common γ-chain (CD132). Recent data suggest that IL-21 possesses proinflammatory properties. However, there is no clear evidence that IL-21 induces inflammation in vivo and, curiously, the interaction between IL-21 and neutrophils has never been investigated, despite the fact that these cells express CD132 and respond to other CD132-dependent cytokines involved in inflammatory disorders. Using the murine air pouch model, we found that IL-21 induced inflammation in vivo, based on recruitment of neutrophil and monocyte populations. In contrast to LPS, administration of IL-21 into the air pouch did not significantly increase the concentration of IL-6, CCL5, CCL3, and CXCL2. We demonstrated that HL-60 cells expressed IL-21Rα, which is down-regulated during their differentiation toward neutrophils, and that IL-21Rα is not detected in neutrophils. Concomitant with this, IL-21 induced Erk-1/2 phosphorylation in HL-60 cells, but not in neutrophils. To eliminate the possibility that IL-21 could activate neutrophils even in the absence of IL-21Rα, we demonstrated that IL-21 did not modulate several neutrophil functions. IL-21-induced Erk-1/2 phosphorylation was not associated with proliferation or differentiation of HL-60 toward neutrophils, monocytes, or macrophages. IL-21Rα was detected in human monocytes and monocyte-derived macrophages, but IL-21 increased CXCL8 production only in monocyte-derived macrophages. We conclude that IL-21 is a proinflammatory cytokine, but not a neutrophil agonist. We propose that IL-21 attracts neutrophils indirectly in vivo via a mechanism independent of IL-6, CCL3, CCL5, and CXCL2 production.