A group led by Dr. You-Yang Zhou at the University of Illinois College of Medicine, Chicago, IL have discovered that caveolin-1 modulation of endothelial nitric oxide synthase (eNOS) activity regulates innate immunity and inflammation-induced lung injury. They present these findings in the May 2010 issue of The American Journal of Pathology.
The innate immune system defends the body against infection in a non-specific manner. Nitric oxide, an antimicrobial agent, and eNOS, an enzyme that produces nitric oxide, play a key role in innate immunity and inflammation, as does caveolin-1, a protein involved in cell signaling. An interaction between caveolin-1 and eNOS is thought to be involved in this process.
To determine the respective roles of caveolin-1 and eNOS in innate immunity and inflammation, Mirza et al generated mice that lacked expression of both caveolin-1 and eNOS. They show that eNOS activation inhibited the immune system in caveolin-1-deficient mice, resulting in a decrease in the levels of proinflammatory molecules and improved survival when compared with mice deficient in both caveolin-1 and eNOS. In addition, eNOS activation in caveolin-1-deficient mice protected against inflammation-induced lung injury. The interaction between caveolin-1 and eNOS may therefore represent a new therapeutic target for inflammation and lung injury.
Dr. Zhou's group "present the first genetic evidence of the physiological significance of [caveolin-1] modulation of eNOS activity in regulating [innate immune] signaling. …[They] show that [caveolin-1] modulation of eNOS activity is a key regulator of innate immunity and inflammatory lung injury."
- Mirza MK, Yuan J, Gao X-P, Garrean S, Brovkovych V, Malik AB, Tiruppathi C, Zhao Y-Y. Caveolin-1 Deficiency Dampens Toll-Like Receptor 4 Signaling through eNOS Activation. American Journal Of Pathology, 2010; 176 (5): 2344 DOI: 10.2353/ajpath.2010.091088
Cite This Page: