OBJECTIVETo study the signaling pathways associated with lipopolysaccharide (LPS)-induced inflammation in islet micro-endothelial cells (IMECs) and the mechanism of pravastatin intervention.

METHODSIMECs exposed to LPS, SB203580, pravastatin, or SB203580+pravastatin were examined for cell apoptosis with Hoechst staining and flow cytometry and for expression levels of total-p38, photophosphorylation-p38 (p-p38) and iNOS with Western blotting.

RESULTSThe apoptosis rate and expression levels of total-p38, p-p38, iNOS in IMECs all increased after LPS exposure. Pravastatin, SB203580, and their combination significantly attenuated LPS-induced enhancement of cell apoptosis and total-p38, p-p38, and iNOS expressions in IMECs.

CONCLUSIONLPS-induced inflammatory toxicity in IMECs is associated with the activation of P38MAPK and iNOS/NO signaling pathways. Pravastatin can inhibit these pathways and suppress the apoptosis and necrosis of IMECs to relieve the cell inflammatory injuries.

Animals ; Apoptosis ; Endothelial Cells ; drug effects ; metabolism ; Endothelium, Vascular ; cytology ; Inflammation ; Islets of Langerhans ; blood supply ; MAP Kinase Signaling System ; drug effects ; Mice ; Nitric Oxide Synthase Type II ; metabolism ; Phosphorylation ; Pravastatin ; pharmacology ; p38 Mitogen-Activated Protein Kinases ; metabolism