Smoke inhalation leads to acute lung injury (ALI), a devastating clinical problem associated with high mortality. Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of apoptosis and pro-inflammatory cytokine signaling, two major contributors to the pathogenesis of ALI. We have found that SOCS-1 protects lung epithelial cells from smoke-induced apoptosis through two mechanisms. One is that SOCS-1 enhances degradation of ASK-1 and diminishes cleavage of pro-caspase-3 to repress smoke-triggered apoptosis in lung epithelial cells. The other is that SOCS-1 represses smoke-triggered DISC formation through altering TRADD-caspase-8 interaction rather than TNFR-1-TRADD interaction or TNFR-1-TRAF-2 interaction. In conclusion, SOCS-1 relieves smoke inhalation-induced lung injury by repressing ASK-1 and DISC-mediated epithelium apoptosis.

吸入烟雾会导致急性肺损伤（ALI），这是与高死亡率相关的毁灭性临床问题。细胞因子信号传导抑制因子1（SOCS-1）是细胞凋亡和促炎性细胞因子信号传导的负调节剂，这是ALI发病机理的两个主要因素。我们发现，SOCS-1通过两种机制保护肺上皮细胞免受烟雾诱导的凋亡。一种是SOCS-1增强ASK-1的降解并减少pro-caspase-3的裂解，从而抑制烟雾触发的肺上皮细胞凋亡。另一个是SOCS-1通过改变TRADD-caspase-8相互作用而不是TNFR-1-TRADD相互作用或TNFR-1-TRAF-2相互作用来抑制烟雾触发的DISC形成。总之，SOCS-1通过抑制ASK-1和DISC介导的上皮细胞凋亡来减轻烟吸入引起的肺损伤。