Rey A, Quartulli F, Escoubet L, Sozzani P, Caput D, Ferrara P, Pipy B
Laboratoire Macrophages, Médiateurs de l'Inflammation et Interactions Cellulaires, Upres E.A 2405, Bâtiment L1, Hôpital de Rangueil, 31403, Toulouse, France.
Biochim Biophys Acta. 1999 Sep 22;1440(2-3):183-93. doi: 10.1016/s1388-1981(99)00121-3.
In a recent investigation, we demonstrated that long-term treatment of macrophages with IL-13 enhances cPLA2 expression and modulates zymosan-stimulated AA mobilization. In the present study, we examine the ability of IL-13 to modify the cPLA2 activity and the AA mobilization of macrophages after a short-period of treatment. We demonstrate that in resting macrophages, IL-13 induces, through a MAP kinase-dependent process, (1) an increase of free AA release within 15 min, followed by increased PGE2 production and (2) a time-dependent serine phosphorylation of cPLA2. Conversely, in macrophages stimulated by zymosan, IL-13 added 30 min before zymosan inhibited the AA release and the serine phosphorylation of cPLA2 induced by the phagocytic agonist. In conclusion, these findings show for the first time that a Th2-type cytokine can upregulate cPLA2 activity and downregulate zymosan-induced AA metabolism. Thus, establishment of the connection between these two events may help to understand the complex regulatory role of IL-13 on the macrophage AA metabolism.
在最近的一项研究中，我们证明用白细胞介素-13长期处理巨噬细胞可增强胞质型磷脂酶A2（cPLA2）的表达，并调节酵母聚糖刺激的花生四烯酸（AA）动员。在本研究中，我们检测了短期处理后白细胞介素-13改变巨噬细胞cPLA2活性和AA动员的能力。我们证明，在静息巨噬细胞中，白细胞介素-13通过丝裂原活化蛋白激酶（MAP激酶）依赖的过程，（1）在15分钟内诱导游离AA释放增加，随后前列腺素E2（PGE2）生成增加，以及（2）cPLA2的丝氨酸磷酸化呈时间依赖性增加。相反，在酵母聚糖刺激的巨噬细胞中，在酵母聚糖刺激前30分钟添加白细胞介素-13可抑制吞噬激动剂诱导的AA释放和cPLA2的丝氨酸磷酸化。总之，这些发现首次表明，Th2型细胞因子可上调cPLA2活性并下调酵母聚糖诱导的AA代谢。因此，建立这两个事件之间的联系可能有助于理解白细胞介素-13对巨噬细胞AA代谢的复杂调节作用。
