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.
Feng
Hong
H
Department of Pediatrics, University of Kentucky Medical School, Lexington, Kentucky 40536, USA.
Guo
Ling
L
Song
Zhiqing
Z
Gao
Haiqing
H
Wang
Dan
D
Fu
Weisi
W
Han
Jingyan
J
Li
Zhenyu
Z
Huang
Bin
B
Li
Xiang-An
XA
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