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TY - JOUR AU - Kang, S J AU - Wang, S. AU - Kuida, K. AU - Yuan, J. PY - 2002 DA - 2002/10/01 TI - Distinct downstream pathways of caspase-11 in regulating apoptosis and cytokine maturation during septic shock response JO - Cell Death & Differentiation SP - 1115 EP - 1125 VL - 9 IS - 10 AB - Caspase-11 is an essential mediator of septic shock response and caspase-11-deficient mice are resistant to LPS-induced shock. Here we report that LPS-induced caspase-11 regulates lymphocyte apoptosis by activating both caspase-3 and caspase-7. The activation of caspase-11 preceded that of caspase-1 and caspases-3/-7, and in the absence of caspase-11, the activation of caspases-3/-7 was significantly reduced. The early activation of caspases-3/-7 by caspase-11 was not affected by blocking of caspase-1 activity and IL-1β release, implying that caspase-11 activates caspases-3/-7 independently of caspase-1 activation. Furthermore, we show that caspase-11-mediated apoptosis under septic condition is Bid-independent. Our work suggests that the human homologue of caspase-11 may be an effective therapeutic target for treatment of septic shock. SN - 1476-5403 UR - https://doi.org/10.1038/sj.cdd.4401087 DO - 10.1038/sj.cdd.4401087 ID - Kang2002 ER -