title: Inhibitors of secreted phospholipase A2 suppress the release of PGE2 in renal mesangial cells.
abstract: 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.
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15771, Greece.
authors.forename: Sofia
authors.initials: S
authors.lastname: Vasilakaki
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15771, Greece.
authors.forename: Efrosini
authors.initials: E
authors.lastname: Barbayianni
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15771, Greece.
authors.forename: Victoria
authors.initials: V
authors.lastname: Magrioti
authors.affiliation: Institute of Pharmacology, University of Bern, Bern 3010, Switzerland.
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Pastukhov
authors.affiliation: Chemical Laboratories, Agricultural University of Athens, Athens 11855, Greece.
authors.forename: Violetta
authors.initials: V
authors.lastname: Constantinou-Kokotou
authors.affiliation: Institute of Pharmacology, University of Bern, Bern 3010, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Huwiler
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15771, Greece. Electronic address: gkokotos@chem.uoa.gr.
authors.forename: George
authors.initials: G
authors.lastname: Kokotos
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D050527:Mesangial Cells / Q000187:drug effects* / Q000201:enzymology; D008954:Models, Biological; D015394:Molecular Structure; D064801:Phospholipase A2 Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors*; D051381:Rats
chemical_list: D064801:Phospholipase A2 Inhibitors; D054497:Phospholipases A2, Secretory; D015232:Dinoprostone
keywords: Inhibitors; Mesangial cells; Phospholipase A(2); Prostaglandin E(2); Secreted phospholipase A(2)