Endogenous TNF-alpha modulates the proliferation of rat mesangial cells and their prostaglandin E2 synthesis.
Mesangial cells (MC) are one cellular source of tumor necrosis factor alpha (TNF) within the kidney as shown by experimental stimulation with endotoxin. TNF was shown to increase MC synthesis of prostaglandins E2 (PGE2) which down regulate MC proliferation. The involvement of endogenous TNF as an autocrine factor to control MC proliferation is unknown. This role was evaluated in vitro by addition of anti-TNF immunoglobulins and soluble TNF receptor-I (sTNF-RI) on rat MC. Anti-TNF immunoglobulins and sTNF-RI induced a dose-dependent increase of cell proliferation when the cells were quiescent in 0.5% FCS P = 0.002). No effect was found when the cells were growing in 10% FCS (P = 0.113). Incubation of MC with anti-TNF immunoglobulins resulted in a dose-dependent decrease of PGE2 release. In order to investigate if the effect of TNF on MC proliferation was mediated by the decrease of PGE2 release, PGE2 was added to the culture medium at concentrations of 0.1 to 10 micrograms/ml in conjunction with anti-TNF immunoglobulins. PGE2 did not modify the proliferation induced by anti-TNF immunoglobulins. We conclude that anti-TNF immunoglobulins and sTNF-RI promoted MC DNA synthesis and influenced their PGE2 release by blocking the endogenous TNF. The mechanism of action on DNA synthesis was not mediated by PGE2. This indicates that endogenous TNF has a substantial role in the control of resting mesangial cells.
Department of Pediatrics, Hôpital Cantonal, Geneva, Switzerland.
N M
NM
Benador
G E
GE
Grau
C
C
Ruef
E P
EP
Girardin
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D005920:Glomerular Mesangium / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000906:Antibodies; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone