HALF-LIFE OF INTERLEUKIN-1-BETA-INDUCED GROUP-II PHOSPHOLIPASE A(2) IN RAT MESANGIAL CELLS

Group II phospholipase A(2) (sPLA(2)) has been implicated as an import ant agent involved in a number of inflammatory processes. Potent pro-i nflammatory cytokines, such as interleukin-1 beta (IL-1 beta) and tumo r necrosis factor (TNF) have been found to induce sPLA(2) synthesis an d release from many cell types among which mesangial cells. Although c onsiderable research has been devoted to unravelling the mechanisms un derlying the induction of sPLA, not much is known about the time scale at which the cytokine elicited signals for sPLA, induction persist in target cells. In this study we addressed that question by using rat r enal mesangial cells as a model target cell. We found that after remov al of IL-1 beta from the culture medium, the induced-sPLA(2) synthesis continues at gradually decreasing rates for approximately 8 h. This i s accompanied by a decrease in sPLA(2) mRNA levels. Furthermore, with pulse-chase experiments we investigated the half-life of sPLA(2) disap pearance from the cells. This disappearance was found to be biphasic. A rapidly disappearing pool, constituting approx. 74% of the total, ex hibited a half-life of 1.6 +/- 0.2 h. The remaining pool of the induce d enzyme was much more stable and its level remained constant for at l east 24 h. Analysis of the appearance of newly synthesized enzyme in t he culture medium indicated this process to be completed in an hour.