SOCS-1 ameliorates smoke inhalation-induced acute lung injury through inhibition of ASK-1 activity and DISC formation

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...

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Published in:Clinical immunology (Orlando, Fla.) Fla.), 2018-06, Vol.191, p.94-99
Main Authors: Zhang, Leifang, Xu, Chenming, Ma, Yating, Zhu, Kairui, Chen, Xiaoming, Shi, Qiwen, Su, Weike, Zhao, Hang
Format: Article
Language:English
Subjects:
Acute Lung Injury - prevention & control
Apoptosis
Apoptosis signal-regulating kinase-1
Caspase 8 - physiology
Cells, Cultured
Death Domain Receptor Signaling Adaptor Proteins - antagonists & inhibitors
Death-inducing signaling complex
Humans
Lung - pathology
MAP Kinase Kinase Kinase 5 - antagonists & inhibitors
Small airway epithelial cells
Smoke Inhalation Injury - prevention & control
Smoke-induced ALI
Suppressor of Cytokine Signaling 1 Protein - physiology
Suppressor of cytokine signaling-1
TNF Receptor-Associated Death Domain Protein - physiology
TNF Receptor-Associated Factor 2 - physiology
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Summary: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. •SOCS-1 protects epithelium cellular viability, enhances ASK-1 degradation, diminishes pro-caspase-3 cleavage and represses DISC formation.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2017.10.014