| First Author | Yuan K | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 24 | Pages | 21814-25 |
| PubMed ID | 21515682 | Mgi Jnum | J:173648 |
| Mgi Id | MGI:5049836 | Doi | 10.1074/jbc.M111.237628 |
| Citation | Yuan K, et al. (2011) Elevated Inflammatory Response in Caveolin-1-deficient Mice with Pseudomonas aeruginosa Infection Is Mediated by STAT3 Protein and Nuclear Factor {kappa}B (NF-{kappa}B). J Biol Chem 286(24):21814-25 |
| abstractText | Caveolin-1 (Cav-1), an important composition protein within the flask-shaped membrane invaginations termed caveolae, may play a role in host defense against infections. However, the phenotype in Pseudomonas aeruginosa-infected cav1 knock-out (KO) mice is still unresolved, and the mechanism involved is almost entirely unknown. Using a respiratory infection model, we confirmed a crucial role played by Cav-1 in host defense against this pathogen because Cav-1 KO mice showed increased mortality, severe lung injury, and systemic dissemination as compared with wild-type (WT) littermates. In addition, cav1 KO mice exhibited elevated inflammatory cytokines (IL-6, TNF-alpha, and IL-12a), decreased phagocytic ability of macrophages, and increased superoxide release in the lung, liver, and kidney. We further studied relevant cellular signaling processes and found that STAT3 and NF-kappaB are markedly activated. Our data revealed that the Cav-1/STAT3/NF-kappaB axis is responsible for a dysregulated cytokine response, which contributes to increased mortality and disease progression. Moreover, down-regulating Cav-1 in cell culture with a dominant negative strategy demonstrated that STAT3 activation was essential for the translocation of NF-kappaB into the nucleus, confirming the observations from cav1 KO mice. Collectively, our studies indicate that Cav-1 is critical for inflammatory responses regulating the STAT3/NF-kappaB pathway and thereby impacting P. aeruginosa infection. |
