Dexamethasone Inhibits Tumor Necrosis Factor-α-Induced Expression of Macrophage Inflammatory Protein-2 and Adhesion of Neutrophils to Endothelial Cells

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 inflammatory and immune cell-mediated responses. We found that tumor necrosis factor-alpha (TNF-alpha) time- and dose-dependently increased gene and protein expression of MIP-2 in endothelial cells. Moreover, it was observed that dexamethasone treatment inhibited endothelial cell expression of MIP-2 in response to TNF-alpha stimulation and markedly reduced the number of adherent neutrophils. Moreover, we found that a monoclonal antibody against murine MIP-2 abolished neutrophil adhesion to TNF-alpha-activated endothelial cells. These data demonstrate that TNF-alpha induces expression of MIP-2 in endothelial cells and support the hypothesis that the anti-inflammatory action of dexamethasone may, at least in part, be attributable to an inhibition of MIP-2 induction on cytokine-activated endothelial cells.