Dexamethasone inhibits tumor necrosis factor-alpha-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.
Liu
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Department of Surgery, Lund University, Malmö, 20502, Sweden.
Wang
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Y
Thorlacius
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H
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002461:Cell Line, Transformed; D054426:Chemokine CXCL2; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D054426:Chemokine CXCL2; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone