Re F, Mengozzi M, Muzio M, Dinarello C A, Mantovani A, Colotta F
Centro Daniela e Catullo Borgomainerio, Milano, Italy.
Eur J Immunol. 1993 Feb;23(2):570-3. doi: 10.1002/eji.1830230242.
After appropriate stimulation, mononuclear phagocytes express a specific inhibitor of interleukin (IL)-1, now re-named IL-1 receptor antagonist (IL-1ra). In this study we have examined the production of IL-1ra by polymorphonuclear cells (PMN). Human PMN isolated from peripheral blood expressed low but detectable levels of IL-1ra transcripts, which were considerably augmented after treatment with lipopolysaccharides (LPS) and cytokines [IL-4, granulocyte (G)- and granulocyte macrophage (GM)-Colony Stimulating factor (CSF), and tumor necrosis factor (TNF)]. The levels of induced IL-1 ra transcripts were comparable to those observed in endotoxin-stimulated human monocytes. By contrast IL-1 beta, interferon (IFN)-gamma and chemotactic factors (fMLP, C5a and IL-8) failed to promote IL-1ra expression in PMN. IL-1ra induction by LPS reached peak levels at 10 ng/ml after 3-6 h and remained sustained 24 h after stimulation. Induction by LPS and GM-CSF appears to be at the transcriptional level, as assessed by inhibiting mRNA synthesis with actinomycin D. Inhibition of protein synthesis by cycloheximide superinduced both basal and inducible IL-1ra mRNA. In addition to expressing mRNA, PMN also produce IL-1ra protein. Secretion of IL-1ra was induced in PMN treated with LPS, IL-4 and GM-CSF, but not by IL-1 beta, IFN-gamma and fMLP, thus yielding results that paralleled those seen in Northern blot experiments. These data indicate that, among myelomonocytic cells, PMN, in addition to mononuclear phagocytes, can express IL-1ra, suggesting that PMN, while exerting a series of pro-inflammatory activities, may also modulate the inflammatory potential of IL-1 in tissues.
经过适当刺激后，单核吞噬细胞会表达一种白细胞介素（IL）-1的特异性抑制剂，现重新命名为IL-1受体拮抗剂（IL-1ra）。在本研究中，我们检测了多形核细胞（PMN）产生IL-1ra的情况。从外周血分离的人PMN表达低水平但可检测到的IL-1ra转录本，在用脂多糖（LPS）和细胞因子[IL-4、粒细胞（G）-和粒细胞巨噬细胞（GM）-集落刺激因子（CSF）以及肿瘤坏死因子（TNF）]处理后，其水平显著增加。诱导的IL-1ra转录本水平与在内毒素刺激的人单核细胞中观察到的水平相当。相比之下，IL-1β、干扰素（IFN）-γ和趋化因子（fMLP、C5a和IL-8）未能促进PMN中IL-1ra的表达。LPS诱导IL-1ra在3 - 6小时后达到10 ng/ml的峰值水平，并在刺激后24小时持续存在。LPS和GM-CSF的诱导似乎在转录水平，这通过用放线菌素D抑制mRNA合成来评估。用环己酰亚胺抑制蛋白质合成会超诱导基础和诱导性IL-1ra mRNA。除了表达mRNA外，PMN还产生IL-1ra蛋白。LPS、IL-4和GM-CSF处理的PMN中诱导了IL-1ra的分泌，但IL-1β、IFN-γ和fMLP未诱导，因此产生的结果与Northern印迹实验中观察到的结果相似。这些数据表明，在骨髓单核细胞中，除了单核吞噬细胞外，PMN也可以表达IL-1ra，这表明PMN在发挥一系列促炎活性的同时，也可能调节组织中IL-1的炎症潜能。
