Interleukin‐1β and transforming growth factor‐β2 enhance cytosolic high‐molecular‐mass phospholipase A2 activity and induce prostaglandin E2 formation in rat mesangial cells

Abstract
Interleukin-1β induces gene expression and secretion of group-II phospholipase A2 and release of prostaglandin E2 from rat mesangial cells. The interleukin-1β-induced synthesis of group-II phospholipase A2 is prevented by transforming growth factor-β2, whereas transforming growth factor-β2 potentiated the interleukin-1β-evoked prostaglandin E2 production. Transforming growth factor-β2 itself did not induce synthesis of group-II phospholipase A2, although it stimulated prostaglandin E2 formation. Here we describe the effect of interleukin-1β and transforming growth factor-β2 on a cytosolic phospholipase A2 activity and prostaglanding E2 formation in rat mesangial cells. Based on the resistance to dithiothreitol and migration profiles on a Mono-Q anion-exchange column and a Superose 12 gel-filtration column, the cytosolic phospholipase A2 activity was assigned to a high-molecular-mass phospholipase A2. Measured with 1-stearoyl-2-[1-14C]arachidonoylglycerophosphocholine as substrate, both interleukin-1β and transforming growth factor-β2 enhanced the high-molecular-mass phospholipase A2 activity. The stimulation of ratmesangial cells with interleukin-1β and transforming growth factor-β2 was time- and dose-dependent with maximal cytosolic phospholipase A2 activities at 10 nM and at 10ng/ml respectively, after 24 h of stimulation. Under these conditions, interleukin-1β and transforming growth factor-β2 enhanced the cytosolic phospholipase A2 activity 2.2 ± 0.6-fold and 2.5 ± 0.6-fold, respectively. These results strongly suggest that an enhanced cytosolic high-molecular-mass phospholipase A2 activity is involved in the formation of prostaglandin E2 mediated by transforming growth factor-β2. Whether interleukin-1β induced group-II phospholipase A2 and/or interleukin-1β-enhanced cytosolic phospholipase A2 activity is involved in prostaglandin E2 formation in rat mesangial cells is discussed.

This publication has 48 references indexed in Scilit: