Inhibitors of secreted phospholipase A2 suppress the release of PGE2 in renal mesangial cells

The upregulation of PGE₂ by mesangial cells has been observed under chronic inflammation condition. In the present work, renal mesangial cells were stimulated to trigger a huge increase of PGE₂ synthesis and were treated in the absence or presence of known PLA₂ inhibitors. A variety of synthetic inhibitors, mainly developed in our labs, which are known to selectively inhibit each of GIVA cPLA₂, GVIA iPLA₂, and GIIA/GV sPLA₂, were used as tools in this study. Synthetic sPLA₂ inhibitors, such as GK115 (an amide derivative based on the non-natural amino acid (R)-γ-norleucine) as well as GK126 and GK241 (2-oxoamides based on the natural (S)-α-amino acid leucine and valine, respectively) presented an interesting effect on the suppression of PGE₂ formation.