Browsing Department of Pharmacology and Toxicology: Faculty Research and Presentations by Authors
The Dual Role of TNF in Pulmonary EdemaYang, Guang; Hamacher, Jürg; Gorshkov, Boris A; White, Richard E.; Sridhar, Supriya; Verin, Alexander D.; Chakraborty, Trinad; Lucas, Rudolf; Department of Pharmacology and Toxicology; Vascular Biology Center (2010)Abstract: Pulmonary edema, a major manifestation of left ventricular heart failure, renal insufficiency, shock, diffuse alveolar damage and lung hypersensitivity states, is a significant medical problem worldwide and can be life-threatening. The proinflammatory cytokine tumor necrosis factor (TNF) has been shown to contribute to the pathogenesis and development of pulmonary edema. However, some recent studies have demonstrated surprisingly that TNF can also promote alveolar fluid reabsorption in vivo and in vitro. This protective effect of the cytokine is mediated by the lectin-like domain of the cytokine, which is spatially distinct from the TNF receptor binding sites. The TIP peptide, a synthetic mimic of the lectin-like domain of TNF, can significantly increase alveolar fluid clearance and improve lung compliance in pulmonary edema models. In this review, we will discuss the dual role of TNF in pulmonary edema.
The role of RhoA/Rho kinase pathway in endothelial dysfunctionYao, Lin; Romero, Maritza J.; Toque, Haroldo A.; Yang, Guang; Caldwell, Ruth B.; Caldwell, Robert William; Department of Pharmacology and Toxicology; Vascular Biology Center (2010)Endothelial dysfunction is a key event in the development of vascular disease, and it precedes clinically obvious vascular pathology. Abnormal activation of the RhoA/Rho kinase (ROCK) pathway has been found to elevate vascular tone through unbalancing the production of vasodilating and vasoconstricting substances. Inhibition of the RhoA/ROCK pathway can prevent endothelial dysfunction in a variety of pathological conditions. This review, based on recent molecular, cellular, and animal studies, focuses on the current understanding of the ROCK pathway and its roles in endothelial dysfunction.