University of British Columbia, Heart Lung Innovation Research Centre, Critical Care Research Laboratories, St. Paul's Hospital, #166-1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada,
Curr Infect Dis Rep. 2013 Oct;15(5):364-71. doi: 10.1007/s11908-013-0362-0.
NF-κB signaling plays a central role in the pathophysiology of severe sepsis and septic shock. Despite tremendous and missed efforts, novel therapeutics for severe sepsis and septic shock are still needed. Many drugs have been designed to target the canonical NF-κB signaling pathway with limited success, potentially due to the nonspecificity of the drugs for other kinases and the interaction of canonical signaling with other pathways. Here, we review the canonical and noncanonical signaling pathways of NF-κB, the cross talk and negative regulation of the two pathways, and the potential for therapeutics arising from the noncanonical NF-κB pathway in relation to the pathophysiology of septic shock.
NF-κB 信号通路在严重脓毒症和感染性休克的病理生理学中起着核心作用。尽管付出了巨大的努力，但仍需要针对严重脓毒症和感染性休克的新疗法。许多药物被设计用于靶向经典 NF-κB 信号通路，但收效甚微，这可能是由于药物对其他激酶的非特异性以及经典信号通路与其他途径的相互作用所致。在这里，我们回顾了 NF-κB 的经典和非经典信号通路、两条通路的串扰和负调控，以及非经典 NF-κB 通路在感染性休克病理生理学方面的治疗潜力。
