Group II phospholipase A2 as an autocrine growth factor mediating interleukin-1 action on mesangial cells.
The proliferation of mesangial cells plays a central role in the progression of glomerulonephritis. We studied the role of group II phospholipase A2 in interleukin-1-stimulated proliferation of mesangial cells. Cultured rat mesangial cells secreted 5.3 units group II phospholipase A2/24 h per 10(5) cells in response to stimulation of 200 U/ml of interleukin-1. Northern hybridization analysis showed that mRNA for group II phospholipase A2 was induced by exogenously added group II phospholipase A2 (15 U/ml) as well as interleukin-1. The pretreatment of quiescent mesangial cells with interleukin-1 augmented [3H]thymidine incorporation caused by platelet derived growth factor. Exogenous group II phospholipase A2 (5-36 U/ml) purified homogeneously from rat spleen also increased [3H]thymidine incorporation by platelet derived growth factor-stimulated mesangial cells in a dose dependent manner (36 U/ml phospholipase A2; 1.9-fold). The stimulatory effect of interleukin-1 on DNA synthesis of mesangial cells was specifically blunted by immunoglobulin raised against group II phospholipase A2. Group II phospholipase A2 (16 U/ml) amplified a platelet derived growth factor-stimulated increase in the mesangial cell number by 1.5-fold. Among the products of the phospholipase A2-catalyzed reaction, lysophospholipids including lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidic acid, but not fatty acids, mimicked the stimulatory effect of interleukin-1 and phospholipase A2. These results suggest that group II phospholipase A2 acts as a signaling molecule that mediates interleukin-1-induced growth of rat mesangial cells through yielding lysophospholipids.
Wada
A
A
First Department of Medicine, Osaka University School of Medicine, Japan.
Tojo
H
H
Sugiura
T
T
Fujiwara
Y
Y
Kamada
T
T
Ueda
N
N
Okamoto
M
M
D000818:Animals; D002452:Cell Count; D002455:Cell Division; D002478:Cells, Cultured / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000201:enzymology; D054501:Group II Phospholipases A2; D006133:Growth Substances / Q000032:analysis*; D007375:Interleukin-1 / Q000494:pharmacology*; D008246:Lysophospholipids / Q000032:analysis; D010741:Phospholipases A / Q000032:analysis* / Q000235:genetics / Q000494:pharmacology; D054467:Phospholipases A2; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D006133:Growth Substances; D007375:Interleukin-1; D008246:Lysophospholipids; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D004247:DNA; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2