Differential expression of @entity11017 / XXXX and potential benefit of an MMP inhibitor in experimental acute kidney allograft rejection.

@entity644 @entity219 @entity6929 @entity35 @entity11017 @entity11556
Acute cellular allograft rejection is characterized by leukocyte invasion and tissue destruction, associated with qualitative and quantitative alterations in the extracellular matrix (ECM) compartment. Metabolism of ECM proteins is mainly regulated by matrix metalloproteinases (MMP), that are @entity219 depended endoproteinases. MMP, especially basement membrane degrading @entity11017 and @entity6929 , also facilitate tissue invasion of leukocytes. In addition, @entity11017 exerts a direct pro-inflammatory effect upon glomerular mesangial cells. Therefore, the investigation of the role of MMP in transplant rejection may lead to novel approaches in the therapy of rejection processes. To our knowledge, this is the first study of acute allograft rejection, formally addressing expression and activity of MMP, including the effect of a MMP inhibiting agent. For our studies, we used the orthotopic kidney allograft model in the stringent Dark Agouti-to-Lewis @entity35 combination. Animals were divided into four groups: group A, healthy untreated Lewis @entity35 (n=3); group B, sham operated Lewis @entity35 (n=3); group C, transplanted Lewis @entity35 treated with vehicle solution only (n=12); group D, transplanted Lewis @entity35 treated with MMP inhibitor @entity11556 (n=12). Respective animals were treated once daily intraperitonealy with @entity11556 (30 mg/kg) or vehicle solution only. Treatment lasted from the third preoperative day until the end of the experiment, the time of severe rejection at day +7. Acute kidney allograft rejection led to alterations in the expression and activity of MMP. Overall MMP activity slightly increased despite severe destruction of kidney histology. The MMP inhibitor @entity11556 successfully inhibited MMP activity to a high extent. MMP expression did not show uniform findings, since acute rejection led to differential expression of @entity11017 and @entity6929 . During the rejection process, @entity6929 showed a small but significant increase, whereas @entity11017 production decreased substantially. Interestingly, @entity11556 was able to keep @entity644 at a low level in transplanted animals. In conclusion, MMP-especially @entity6929 -appear to represent new mediators involved in acute kidney transplant rejection.
