Intrinsic cyclooxygenase activity is not required for monocytic differentiation of U937 cells.
Metabolism of arachidonic acid has been found to modulate cell growth and differentiation. Since differentiation of premonocytic U937 cells is paralleled by increase expression of cyclooxygenase and prostanoid synthesis, we assessed the role of cyclooxygenase in the differentiation of U937 cells. Treatment with retinoic acid (RA, 1 microM) or 1,250(OH)2-vitamin D3 (1,25-D3, 10 nM) increased the expression of the monocytic surface antigens CD11b plus CD11c, and CD11b, CD11c, CD14 plus CD18, respectively. Addition of the cyclooxygenase inhibitors indomethacin (10 microM) or piroxicam (20 microM) slightly increased expression of CD11b and CD18 in cells differentiated with RA, but did not alter expression of surface antigens in cells treated with 1,25-D3. Stimulus-dependent rises in the cytosolic-free calcium concentrations remained unchanged by the inhibitors, as was superoxide anion generation in cells stimulated with phorbol myristate acetate. Effective inhibition of cyclooxygenase over the 72 h of differentiation was proven by the marked decrease in A23187-stimulated prostanoid formation in differentiated cells. To assess whether prostaglandins negatively control monocytic differentiation, as suggested by the stimulatory effects of cyclooxygenase inhibitors on CD11b/CD18 expression in RA-treated cells, prostaglandin E2 (PGE2; 100 nM) was added to the differentiation with RA or 1,25-D3. However, the addition of PGE2 increased expression of CD11b and CD11b plus CD14, as well as superoxide anion generation. These data indicate that intrinsic cyclooxygenase activity is not required for monocytic differentiation of U937 cells. In addition, basal prostanoid secretion does not measurably contribute to monocytic differentiation.
Sellmayer
A
A
Institut für Prophylaxe und Epidemiologie der Kreislaufrankheiten, Universität München, Germany.
Obermeier
H
H
Weber
C
C
D015703:Antigens, CD / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D010894:Piroxicam / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D013481:Superoxides / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D013481:Superoxides; D010894:Piroxicam; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D002118:Calcium; D007213:Indomethacin