| First Author | Sarkar A | Year | 2006 |
| Journal | Am J Respir Crit Care Med | Volume | 174 |
| Issue | 9 | Pages | 1003-10 |
| PubMed ID | 16908867 | Mgi Jnum | J:135846 |
| Mgi Id | MGI:3794673 | Doi | 10.1164/rccm.200604-546OC |
| Citation | Sarkar A, et al. (2006) Caspase-1 regulates Escherichia coli sepsis and splenic B cell apoptosis independently of interleukin-1beta and interleukin-18. Am J Respir Crit Care Med 174(9):1003-10 |
| abstractText | RATIONALE: Caspase-1 processes interleukin 1beta (IL-1beta) and IL-18 but may also contribute to apoptosis. In this context, caspase-1 knockout mice have been shown to be protected from endotoxin-induced mortality, whereas IL-1beta knockout mice are not protected. OBJECTIVES: We therefore sought to delineate the mechanisms responsible for the differential responses between caspase-1 and IL-1beta knockout mice. METHODS: Caspase-1 knockout, IL-1beta knockout, and IL-1beta/IL-18 double knockout mice were compared with wild-type mice for survival after intraperitoneal challenge with live Escherichia coli. MEASUREMENTS AND MAIN RESULTS: Caspase-1 knockout animals were protected from bacterial challenge, whereas wild-type, IL-1beta knockout, and IL-1beta/IL-18 double knockout animals were not. Wild-type animals and both IL-1beta knockout and IL-1beta/IL-18 double knockout mice demonstrated significant splenic B lymphocyte apoptosis, which was absent in the caspase-1 knockout mice. Importantly, IL-1beta/IL-18 double knockout mice were protected from splenic cell apoptosis and sepsis-induced mortality by the caspase inhibitor zVAD-fmk. Furthermore, wild-type but not caspase-1 knockout splenic B lymphocytes induced peritoneal macrophages to assume an inhibitory phenotype. CONCLUSION: Taken together, these findings suggest that caspase-1 is important in the host response to sepsis at least in part via its ability to regulate sepsis-induced splenic cell apoptosis. |
