Dexamethasone inhibits tumor necrosis factor-alpha-induced expression of macrophage inflammatory protein-2 and adhesion of neutrophils to endothelialcells

Macrophage inflammatory protein-2 (MIP-2) belongs to the C-X-C subfamily of chemokines and appears to play an important role in cytokine-induced infla mmatory and immune cell-mediated responses. We found that tumor necrosis fa ctor-alpha (TNF-alpha) time- and dose-dependently increased gene and protei n expression of MIP-2 in endothelial cells. Moreover, it was observed that dexamethasone treatment inhibited endothelial cell expression of MIP-2 in r esponse to TNF-alpha stimulation and markedly reduced the number of adheren t neutrophils. Moreover, we found that a monoclonal antibody against murine MIP-2 abolished neutrophil adhesion to TNF-alpha-activated endothelial cel ls. These data demonstrate that TNF-alpha induces expression of MIP-2 in en dothelial cells and support the hypothesis that the anti-inflammatory actio n of dexamethasone may at least in part, be attributable to an inhibition o f MIP-2 induction on cytokine-activated endothelial cells. (C) 2000 Academi c Press.