Regulation of Vascular Responses to Inflammation: Inducible Matrix Metalloproteinase-3 Expression in Human Microvascular Endothelial Cells Is Sensitive to AntiinflammatoryBoswellia

Endothelial cells are critical elements in the pathophysiology of inflammation. Tumor necrosis factor (TNF) α potently induces inflammatory responses in endothelial cells. Recently we have examined the genetic basis of the antiinflammatory effects of Boswellia extract (BE) in a system of TNFα-induced gene expression in human microvascular endothelial cells (HMECs). Of the 522 genes induced by TNFα in HMECs, 113 genes were sensitive to BE. BE prevented the TNFα-induced expression of matrix metalloproteinases (MMPs). In the current work, we sought to test the effects of BE on TNFα-inducible MMP expression in HMECs. Acetyl-11-ketobeta- boswellic acid (AKBA) is known to be an active principle in BE. To evaluate the significance of AKBA in the antiinflammatory properties of BE, effects of BE containing either 3% (BE3%) or 30% (BE30%, 5- Loxin®) were compared. Pretreatment of HMECs for 2 days with BE potently prevented TNFα-induced expression and activity of MMP-3, MMP-10, and MMP-12. In vivo, BE protected against experimental arthritis. In all experiments, both in vitro and in vivo, BE30% was more effective than BE3%. In sum, this work lends support to our previous report that BE has potent antiinflammatory properties both in vitro as well as in vivo.