Caveolin-1 is critical regulator of innate immunity

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."