Dexamethasone and hydrogen peroxide production by mesangial cells during phagocytosis.
We have previously demonstrated that a high percentage of rat cultured mesangial cells phagocytized serum-treated zymosan (STZ) (L. Baud, J. Hagege, J. Sraer, E. Rondeau, J. Perez, and R. Ardaillou, J. Exp. Med. 158: 1836-1852, 1983). Phagocytosis resulted in stimulation of arachidonic acid metabolism with generation of H2O2. Exposure of mesangial cells to dexamethasone for 48 h produced a dose-dependent decrease in phagocytosis-induced production of H2O2 with a 50% inhibitory concentration of 32 nM. The decrease in H2O2 release was associated with the inhibition of prostaglandin (PG) E2 production. The effect of dexamethasone could be considered as due to receptor-mediated modulation of protein synthesis since dexamethasone was not active immediately but only after a lag period of 3 h; RU 38486, a potent competitor for dexamethasone receptors, counteracted the reduction in H2O2 generation; and actinomycin and cycloheximide both blunted the inhibitory effect of dexamethasone. Pretreatment of mesangial cells with dexamethasone also produced a dose-dependent decrease in the phagocytic capability of the cells (63% inhibition for 1 microM dexamethasone). However, the inhibitory effect of dexamethasone on H2O2 production expressed as percentage of control was similar whether or not phagocytosis had been blocked by cytochalasin B. This result and also the fact that dexamethasone inhibited H2O2 production in cells triggered with soluble stimuli (A 23187 ionophore, PAF) suggested that the effect of dexamethasone on H2O2 generation was independent of that on phagocytosis. Addition of exogenous arachidonic acid reduced the effect of dexamethasone only when its conversion into PGE2 was inhibited by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
Baud
L
L
Perez
J
J
Ardaillou
R
R
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone; D004963:Estrenes / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000096:biosynthesis*; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015735:Mifepristone; D010587:Phagocytosis; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D015054:Zymosan
D001095:Arachidonic Acids; D004963:Estrenes; D011458:Prostaglandins E; D003609:Dactinomycin; D016718:Arachidonic Acid; D015735:Mifepristone; D003907:Dexamethasone; D015054:Zymosan; D003513:Cycloheximide; D006861:Hydrogen Peroxide; D015232:Dinoprostone