Upregulation of group IB secreted phospholipase A2 and its M-type receptor in rat ANTI-THY-1 glomerulonephritis

Treatment of rat glomerular mesangial cell (GMC) cultures with pancreatic secreted phospholipase A 2 (sPLA 2 -IB) results in an enhanced expression of sPLA 2 -IIA and COX-2, possibly via binding to its specific M-type sPLA 2 receptor. In the current study, we have investigated the expression and regulation of sPLA 2 -IB and its receptor during glomerulonephritis (GN). In vivo we used the well-established rat model of anti-Thy 1.1 GN (anti-Thy 1.1-GN) to study the expression of sPLA 2 -IB and the M-type sPLA 2 receptor by immunohistochemistry. In addition, in vitro we determined the interkeukin (IL)-1 β -regulated mRNA and protein expression in primary rat glomerular mesangial and endothelial cells as well as in rat peripheral blood leukocytes (PBLs). Shortly after induction of anti-Thy 1.1-GN, sPLA 2 -IB expression was markedly upregulated in the kidney at 6–24h. Within glomeruli, the strongest sPLA 2 -IB protein expression was detected on infiltrated granulocytes and monocytes. However, at the same time, the M-type receptor was also markedly upregulated on resident glomerular cells. In vitro , the most prominent cytokine-stimulated secretion of sPLA 2 -IB was observed in monocytes isolated from rat PBLs. Treating glomerular endothelial cells (GECs) with cytokines elicited only weak sPLA 2 -IB expression, but treatment of these cells with exogenous sPLA 2 -IB resulted in a marked expression of the endogenous sPLA 2 -IB. Mesangial cells did not express sPLA 2 -IB at all. The M-type sPLA 2 receptor protein was markedly upregulated on cytokine-stimulated mesangial and endothelial cells as well as on lymphocytes and granulocytes. During anti-Thy 1.1 rat GN, sPLA 2 -IB and the M-type sPLA 2 receptor are induced as primary downstream genes stimulated by inflammatory cytokines. Subsequently, both sPLA 2 -IB and the M-type sPLA 2 receptor are involved in the autocrine and paracrine amplification of the inflammatory process in different resident and infiltrating cells.