Mesangial cells release untransformed prostaglandin H2 as a major prostanoid.
BACKGROUND
Prostaglandin H2 (PGH2) is the precursor of the other prostanoids and exhibits a vasoconstricting activity. Glomerular mesangial cells are an important source of vasoactive prostanoids in kidney. Hence, the present investigation focused on the release of untransformed PGH2 by rat glomerular mesangial cells (RGMCs).


METHODS
Synthesis of prostanoid by resting and interleukin-1beta (IL-1beta)-treated (overnight) RGMCs from exogenous or endogenous arachidonic acid (AA) was assessed by high-performance liquid chromtography or enzyme immunoassay, respectively. Cyclo-oxygenase isoforms were determined by Western blotting. Release of untransformed PGH2 from exogenous AA was evaluated in RGMCs and intact glomeruli as the difference of PGF2alpha formed in the incubations performed in the presence and in the absence of SnCl2 or measuring the ability of aspirin-treated platelets to form thromboxane B2 (TXB2) in mixed incubations of platelets and RGMCs or glomeruli.


RESULTS
The prostanoids formed by RGMCs were PGE2, PGF2alpha, PGI2 and PGD2. SnCl2 totally deviated formation of PGE2 and PGD2 toward PGF2alpha in resting RGMCs, whereas PGE2 was only partially deviated toward PGF2alpha in IL-1beta-treated RGMCs. The PGE2/PGD2 ratio in resting RGMCs was similar to that expected for nonenzymatic isomerization of PGH2, whereas this ratio was higher in IL-1beta-treated RGMCs, suggesting the induction of PGE synthase by IL-1beta. Aspirin-treated platelets formed TXB2 when either RGMCs or intact glomeruli were present in the incubation and formation of TXB2 was approximately fourfold higher with IL-1beta-treated RGMCs or glomeruli.


CONCLUSIONS
RGMCs and intact glomeruli released substantial amounts of untransformed PGH2, which was enhanced following exposure to IL-1beta.
Laboratori de Mediadors de la Inflamació, Institut de Recerca de Hospital de la Santa Creu i Sant Pau, Fundació Puigvert, Barcelona, Spain.
M
M
Soler
M
M
Camacho
R
R
Solá
L
L
Vila
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007375:Interleukin-1; D011463:Prostaglandins H; D016718:Arachidonic Acid; D044262:Prostaglandin H2