Regulation of Vascular Responses to Inflammation: Inducible Matrix Metalloproteinase-3 Expression in Human Microvascular Endothelial Cells Is Sensitive to Anti-Inflammatory Boswellia
Roy, Sashwati & Khanna, Savita & Alluri, Kr & Subbaraju, Gottumukkala & Yasmin, Taharat & Bagchi, Debasis & Sen, Chandan
(2006) ANTIOXIDANTS & REDOX SIGNALING. 8. 653-60. 10.1089/ars.2006.8.653.
Endothelial cells are critical elements in the pathophysiology of inflammation. Tumor necrosis factor (TNF) potently induces inflammatory responses in endothelial cells. Recently we have examined the genetic basis of the anti-inflammatory effects of Boswellia extract (BE) in a system of TNF_-induced gene expression in human microvascular endothelial cells (HMECs). Of the 522 genes induced by TNF_ in HMECs, 113 genes were sensitive to BE. BE prevented the TNF_-induced expression of matrix metalloproteinases (MMPs).
In the current work, we sought to test the effects of BE on TNF_-inducible MMP expression in HMECs. Acetyl-11-keto-beta-boswellic acid (AKBA) is known to be an active principle in BE. To evaluate the significance of AKBA in the anti-inflammatory properties of BE, effects of BE containing either 3% (BE3%) or 30% (BE30%) were compared. Pretreatment of HMECs for 2 days with BE potently prevented TNF_-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 anti-inflammatory properties both in vitro as well as in vivo.