The expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 in @entity1 macrophages is inhibited by the anti-atherogenic cytokine @entity2533 and requires Smads, @entity1435 mitogen-activated protein kinase and XXXX .

@entity1 @entity26 @entity2533 @entity1178 @entity27369 @entity1435 @entity731
@entity731 is an inflammatory disorder of the vasculature that is orchestrated by the action of cytokines. Macrophages play a prominent role in all stages of this disease, including foam cell formation, production of reactive @entity26 species, modulation of the inflammatory response and the regulation of the stability of @entity731 . The role of the matrix metalloproteinase family in the control of plaque stability is well established. A disintegrin and metalloproteinase with thrombospondin motif (ADAMTS) family has been implicated in several diseases and the expression of @entity27369 in macrophages of @entity731 has suggested a potential role for this protease in @entity731 . However, the action of cytokines on the expression of @entity27369 in macrophages is poorly understood. We have investigated here the effect of @entity2533 ( @entity2533 ) on @entity27369 expression in macrophages along with the regulatory mechanisms underlying its actions. Consistent with the anti-atherogenic role of @entity2533 , this cytokine decreased the expression of @entity27369 mRNA and protein in @entity1 macrophages. Transient transfection assays showed that the -100 to +10 promoter region contained the minimal @entity2533 response elements. Small-interfering RNA-mediated knockdown revealed a critical role for Smads, @entity1435 mitogen-activated protein kinase and @entity1178 in the action of @entity2533 on @entity27369 mRNA expression. These studies show for the first time that @entity2533 inhibits the expression of @entity27369 in @entity1 macrophages and identifies the signalling pathways underlying this response. The inhibition of macrophage @entity27369 expression is likely to contribute to the anti-atherogenic, plaque stabilisation action of @entity2533 .
