IL-13 induces serine phosphorylation of cPLA2 in mouse peritoneal macrophages leading to arachidonic acid and PGE2 production and blocks the zymosan-induced serine phosphorylation of cPLA2 and eicosanoid production

In a recent investigation, we demonstrated that long-term treatment of macr ophages with IL-13 enhances cPLA2 expression and modulates zymosan-stimulat ed AA mobilization. In the present study, we examine the ability of IL-13 t o modify the cPLA2 activity and the AA mobilization of macrophages after a short-period of treatment. We demonstrate that in resting macrophages, IL-1 3 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 t ime-dependent serine phosphorylation of cPLA2. Conversely, in macrophages s timulated by zymosan, IL-13 added 30 min before zymosan inhibited the AA re lease and the serine phosphorylation of cPLA2 induced by the phagocytic ago nist. 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 macroph age AA metabolism. (C) 1999 Elsevier Science B.V. All rights reserved.