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 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.
Rey
A
A
Laboratoire Macrophages, Médiateurs de l'Inflammation et Interactions Cellulaires, Upres E.A 2405, Bâtiment L1, Hôpital de Rangueil, 31403, Toulouse, France.
Quartulli
F
F
Escoubet
L
L
Sozzani
P
P
Caput
D
D
Ferrara
P
P
Pipy
B
B
D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis*; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction; D015054:Zymosan / Q000037:antagonists & inhibitors*
D005419:Flavonoids; D018793:Interleukin-13; D016718:Arachidonic Acid; D012694:Serine; D015054:Zymosan; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010741:Phospholipases A; D015232:Dinoprostone; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium