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 c ells. Exogenous NO augmented release of chemokines from human promonocytic U937 cells and peripheral blood mononuclear cells. Pharmacological strategi es aiming at modulation of NO-induced release of interleukin-8 (IL-8) were investigated in U937 cells in detail. Release of IL-g was down-regulated by transforming growth factor beta2 (TGF-beta2), by the protein tyrosine-kina se inhibitor genistein, and via rises in intracellular cyclic AMP, generate d by prostaglandin E-2, rolipram, pentoxifylline, forskolin, or dibutyryl-c yclic AMP. In addition, incubation with the synthetic glucocorticoid dexame thasone or suppression of activity of p38 mitogen-activated protein (MAP) k inases by SB-203580 modulated release of IL-8. Activation of p38 MAP kinase s was confirmed by the demonstration of an augmented appearance of phosphor ylated 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, dexa methasone. and SB-203580 modulate inflammatory, chemokine-inducing actions of NO. (C) 2000 Elsevier Science Inc.