Silencing of C5a receptor gene with siRNA for protection from Gram-negative bacterial lipopolysaccharide-induced vascular permeability.

Endothelial barrier dysfunction leading to increased permeability and vascular leakage is an underlying cause of several pathological conditions. Whereas these changes have been shown to be associated with activation of the complement system, leading to the release of C5a and interaction of C5a-C5a receptor (C5aR), the role of C5aR in endothelial cells remain(s) ill-defined. Here, we report an essential role of C5aR in endothelial cell injury and vascular permeability through silencing of the C5aR gene using siRNA.

Small interfering RNA-directed targeting of Toll-like receptor 4 inhibits human prostate cancer cell invasion, survival, and tumorigenicity.

A major cause of tumor treatment failure is cancer cell metastasis. Toll-like receptor 4 (TLR4)-mediated signaling has been implicated in tumor cell invasion, survival, and metastasis in a variety of cancers. In this study, we investigated the biological roles of TLR4 in prostate metastatic cell invasion and survival, and the potential of gene silencing of TLR4 using small interfering RNA (siRNA) for treatment of cancer.

Anti-vascular permeability of the cleaved reactive center loop within the carboxyl-terminal domain of C1 inhibitor.

C1 inhibitor (C1INH), a member of the serine proteinase inhibitor (serpin) family, functions as an inhibitor of the complement and contact systems. Cleavage of the reactive center loop (RCL) within the carboxyl-terminal domain of C1INH (iC1INH), lacking of serpin function, induces a conformational change in the molecule. Our previous data demonstrated that active, intact C1INH prevents vascular permeability induced by gram-negative bacterial lipopolysaccharide (LPS).