Induction of prostaglandin E2 by human monocytes infected with Mycobacterium avium complex--modulation of cytokine expression.
Prostanoids, including prostaglandin E2 (PGE2), suppress macrophage effector functions against Mycobacterium tuberculosis. PGE2 production by monocytes infected with Mycobacterium avium complex (MAC) and its effects on intracellular mycobacterial growth were examined. Freshly obtained monocytes from healthy subjects were stimulated with lipopolysaccharide or 10(7) organisms/mL of 4 MAC strains. PGE2 production in monocyte supernatants peaked at 48 h. Significantly higher levels of PGE2 were produced by monocytes infected with the mixed rough-smooth, flat, and transparent (SmT) morphotype strain 86m2096 (26.8 +/- 5.2 ng/mL) than by the more virulent LR114 SmT morphotype strain (2.4 +/- 0.6 ng/mL; P < .05, paired t test). When infected monocytes were incubated with 1 microgram/mL indomethacin (IM) for 2 days and then further stimulated with interferon-gamma, no effect on intracellular MAC growth was evident. IM increased tumor necrosis factor-alpha (1.7 +/- 0.4 vs. 2.3 +/- 0.3 ng/mL; P = .005, paired t test) but not interleukin-1 beta (8.2 +/- 1.7 vs. 8.7 +/- 2.1 ng/mL, P = .34) production by monocytes stimulated with lipopolysaccharide. These data suggest that MAC-induced PGE2 expression may modulate cytokine production and intracellular parasitism.
Venkataprasad
N
N
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4984, USA.
Shiratsuchi
H
H
Johnson
J L
JL
Ellner
J J
JJ
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000378:metabolism* / Q000382:microbiology; D015269:Mycobacterium avium Complex / Q000187:drug effects / Q000254:growth & development*
D016207:Cytokines; D008070:Lipopolysaccharides; D007371:Interferon-gamma; D015232:Dinoprostone; D007213:Indomethacin