TREM-1 inhibition or ondansetron administration ameliorates NLRP3 inflammasome and pyroptosis in traumatic brain injury-induced acute lung injury

TREM-1 抑制剂或昂丹司琼给药可改善创伤性脑损伤引起的急性肺损伤中的 NLRP3 炎症小体和细胞焦亡

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作者:Fen Li, Na Qin, Yiqin Yu, Rui Dong, Xiaojie Li, Shenhai Gong, Zhenhua Zeng, Lin Huang, Hong Yang

Conclusions

Ondansetron alleviated TBI-ALI. In terms of mechanism, TREM-1 promotes TBI-ALI via the NLRP3-related pyroptosis pathway, and the protective effect of ondansetron on TBI-ALI may be related to the inhibition of TREM-1.

Material and methods

A TBI-ALI rat model was constructed via lateral fluid percussion (LFP) brain injury, and either TREM-1 inhibitor (LP17) or ondansetron was administered as needed.

Methods

A TBI-ALI rat model was constructed via lateral fluid percussion (LFP) brain injury, and either TREM-1 inhibitor (LP17) or ondansetron was administered as needed.

Results

TBI induced NLRP3 inflammasome, pyroptosis, and TREM-1 activation in rat lung tissues in a time-dependent manner. Inhibition of TREM-1 activity attenuated TBI-ALI; this is evident from reduced pathological scores, wet/dry ratios, and bronchoalveolar lavage fluid protein levels and alleviated NLRP3 inflammasome/pyroptosis. In addition, ondansetron reduced NLRP3 inflammasome/pyroptosis and alleviated TBI-ALI. Moreover, ondansetron reduced TREM-1 activation in macrophages and lung tissue. Conclusions: Ondansetron alleviated TBI-ALI. In terms of mechanism, TREM-1 promotes TBI-ALI via the NLRP3-related pyroptosis pathway, and the protective effect of ondansetron on TBI-ALI may be related to the inhibition of TREM-1.

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