Caveolin-1 protects against sepsis by modulating inflammatory response, alleviating bacterial burden, and suppressing thymocyte apoptosis.
Sepsis is a leading cause of death, which is characterized by uncontrolled inflammatory response. In this study, we report that caveolin-1, a major component of caveolae, is a critical survival factor of sepsis. We induced sepsis using a well established sepsis animal model, cecal ligation and puncture (CLP). CLP induced 67% fatality in caveolin-1 null mice, but only 27% fatality in wild type littermates (p = 0.015). Further studies revealed that mice deficient in caveolin-1 exhibited marked increase in tumor necrosis factor-alpha and interleukin-6 production 20 h following CLP treatment, indicating uncontrolled inflammatory responses in the absence of caveolin-1. Caveolin-1 null mice also had a significant increase in bacteria number recovered from liver and spleen, indicating elevated bacterial burdens. In addition, caveolin-1 null mice had a 2-fold increase in thymocyte apoptosis compared with wild type littermates, indicating caveolin-1 as a critical modulator of thymocyte apoptosis during sepsis. In conclusion, our findings demonstrate that caveolin-1 is a critical protective modulator of sepsis in mice. Caveolin-1 exerts its protective function likely through its roles in modulating inflammatory response, alleviating bacterial burdens, and suppressing thymocyte apoptosis.
Department of Pediatrics, University of Kentucky Medical School, Lexington, Kentucky 40536, USA.
Hong
H
Feng
Ling
L
Guo
Zhiqing
Z
Song
Haiqing
H
Gao
Dan
D
Wang
Weisi
W
Fu
Jingyan
J
Han
Zhenyu
Z
Li
Bin
B
Huang
Xiang-An
XA
Li
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007416:Intestinal Perforation / Q000150:complications; D008026:Ligation; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011677:Punctures; D018805:Sepsis / Q000209:etiology / Q000276:immunology* / Q000382:microbiology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*
D051242:Caveolin 1; D016207:Cytokines; D009569:Nitric Oxide; D009195:Peroxidase