Half-life of interleukin-1 beta-induced group II phospholipase A2 in rat mesangial cells

Group II phospholipase A2 (sPLA2) has been implicated as an important agent involved in a number of inflammatory processes. Potent pro-inflammatory cytokines, such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) have been found to induce sPLA2 synthesis and release from many cell types among which mesangial cells. Although considerable research has been devoted to unravelling the mechanisms underlying the induction of sPLA2 not much is known about the time scale at which the cytokine elicited signals for sPLA2 induction persist in target cells. In this study we addressed that question by using rat renal mesangial cells as a model target cell. We found that after removal of IL-1 beta from the culture medium, the induced-sPLA2 synthesis continues at gradually decreasing rates for approximately 8 h. This is accompanied by a decrease in sPLA2 mRNA levels. Furthermore, with pulse-chase experiments we investigated the half-life of sPLA2 disappearance from the cells. This disappearance was found to be biphasic. A rapidly disappearing pool, constituting approx. 74% of the total, exhibited a half-life of 1.6 +/- 0.2 h. The remaining pool of the induced enzyme was much more stable and its level remained constant for at least 24 h. Analysis of the appearance of newly synthesized enzyme in the culture medium indicated this process to be completed in an hour.