| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T39977 | ||||
| Target Name | Macrophage migration inhibitory factor | ||||
| Target Type | Clinical Trial |
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| Action against Disease Model | COR100140 | Chemical inhibitors of MIF enzymatic activity:In vitro activity, COR100140 inhibited IL-1-induced synovial fibroblast proliferation of RA patients and IL-1-induced fibroblast expression of COX-2. | [552554] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | K/BxN ser uM-transfer arthritis was markedly attenuated in Macrophage migration inhibitory factor knockout,MIF(-/-) mice, with reductions in the clinical and histologic severityof arthritis and the synovial expression of KC and interleukin-1. Arthritis was also reduced by anti-KC antibody treatment, but not in MCP-1-deficient mice. In vivo, neutrophil recruitment responses to KC were reduced in MIF(-/-) mice. Similarly, MIF(-/-) mouse neutrophils exhibited reduced chemotactic responses to KC in vitro, despite displaying unaltered chemokine receptor expression. Reduced chemotactic responses of MIF(-/-) mouse neutrophils were associated with reduced phosphorylation of p38 and ERK MAP kinases.These findings suggest that MIF promotes neutrophil trafficking in inflammatory arthritis via facilitation of chemokine-induced migratory responses and MAP kinase activation. Therapeutic MIF inhibition could limit synovial neutrophil recruitment. | [552554] | |||
| References | |||||
| Ref 552554 | Macrophage migration inhibitory factor is a determinant of hypoxia-induced apoptosis in colon cancer cell lines. Clin Cancer Res. 2005 Oct 15;11(20):7264-72. | ||||
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