Upregulation of group IB secreted phospholipase A(2) 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)-1beta-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 6-24 h. 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.
Beck
S
S
Pharmazentrum frankfurt, University Hospital, JW Goethe-University, Frankfurt, Germany. sbeck@em.uni-frankfurt.de
Beck
G
G
Ostendorf
T
T
Floege
J
J
Lambeau
G
G
Nevalainen
T
T
Radeke
H H
HH
Gurrieri
S
S
Haas
U
U
Thorwart
B
B
Pfeilschifter
J
J
Kaszkin
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D007518:Isoantibodies; D007668:Kidney / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010179:Pancreas / Q000201:enzymology; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D054507:Receptors, Phospholipase A2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D007518:Isoantibodies; C516357:Pla2r1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054507:Receptors, Phospholipase A2; C035678:anti-Thy antibody; D051546:Cyclooxygenase 2; D010741:Phospholipases A