Nitric oxide augments release of chemokines from monocytic U937 cells: modulation by anti-inflammatory pathways.
Nitric oxide (NO) appears to act as an inflammatory mediator on monocytic cells. Exogenous NO augmented release of chemokines from human promonocytic U937 cells and peripheral blood mononuclear cells. Pharmacological strategies aiming at modulation of NO-induced release of interleukin-8 (IL-8) were investigated in U937 cells in detail. Release of IL-8 was down-regulated by transforming growth factor beta2 (TGF-beta2), by the protein tyrosine-kinase inhibitor genistein, and via rises in intracellular cyclic AMP, generated by prostaglandin E(2), rolipram, pentoxifylline, forskolin, or dibutyryl-cyclic AMP. In addition, incubation with the synthetic glucocorticoid dexamethasone or suppression of activity of p38 mitogen-activated protein (MAP) kinases by SB-203580 modulated release of IL-8. Activation of p38 MAP kinases was confirmed by the demonstration of an augmented appearance of phosphorylated p38 in the presence of NO. The present data suggest that exposure to exogenous NO resembles activation of U937 cells by proinflammatory stimuli. The anti-inflammatory cytokine TGF-beta2, as well as anti-inflammatory or immunosuppressive agents such as genistein, pentoxifylline, rolipram, dexamethasone, and SB-203580 modulate inflammatory, chemokine-inducing actions of NO.
Mühl
H
H
Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main, Theodor-Stern-Kai 7, D-65090 am Main, Frankfurt, Germany. H.Muehl@em.uni-frankfurt.de
Chang
J H
JH
Huwiler
A
A
Bosmann
M
M
Paulukat
J
J
Ninic
R
R
Nold
M
M
Hellmuth
M
M
Pfeilschifter
J
J
D054407:Chemokine CCL4; D018925:Chemokines / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D016209:Interleukin-8 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014226:Triazenes / Q000494:pharmacology; D020298:U937 Cells; D048051:p38 Mitogen-Activated Protein Kinases
C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D054407:Chemokine CCL4; D018925:Chemokines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D020030:Nitric Oxide Donors; D011725:Pyridines; D016212:Transforming Growth Factor beta; D014226:Triazenes; D009569:Nitric Oxide; D003907:Dexamethasone; D019833:Genistein; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate; C093642:SB 203580