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- Title
5-Methoxytryptophan ameliorates endotoxin-induced acute lung injury in vivo and in vitro by inhibiting NLRP3 inflammasome-mediated pyroptosis through the Nrf2/HO-1 signaling pathway.
- Authors
Ma, Yang; Wang, Zhixue; Wu, Xiaoyang; Ma, Zijian; Shi, Jia; He, Simeng; Li, Shaona; Li, Xiangyun; Li, Xiangkun; Li, Yan; Yu, Jianbo
- Abstract
Background and aim: Endotoxin-induced acute lung injury (ALI) is a complicated and fatal condition with no specific or efficient clinical treatments. 5-Methoxytryptophan (5-MTP), an endogenous metabolite of tryptophan, was revealed to block systemic inflammation. However, the specific mechanism by which 5-MTP affects ALI still needs to be clarified. The purpose of this study was to determine whether 5-MTP protected the lung by inhibiting NLRP3 inflammasome-mediated pyroptosis through the Nrf2/HO-1 signaling pathway. Methods and results: We used lipopolysaccharide (LPS)-stimulated C57BL/6 J mice and MH-S alveolar macrophages to create models of ALI, and 5-MTP (100 mg/kg) administration attenuated pathological lung damage in LPS-exposed mice, which was associated with decreased inflammatory cytokines and oxidative stress levels, upregulated protein expression of Nrf2 and HO-1, and suppressed Caspase-1 activation and NLRP3-mediated pyroptosis protein levels. Moreover, Nrf2-deficient mice or MH-S cells were treated with 5-MTP to further confirm the protective effect of the Nrf2/HO-1 pathway on lung damage. We found that Nrf2 deficiency partially eliminated the beneficial effect of 5-MTP on reducing oxidative stress levels and inflammatory responses and abrogating the inhibition of NLRP3-mediated pyroptosis induced by LPS. Conclusion: These findings suggested that 5-MTP could effectively ameliorate ALI by inhibiting NLRP3-mediated pyroptosis via the Nrf2/HO-1 signaling pathway.
- Subjects
PYROPTOSIS; NLRP3 protein; CELLULAR signal transduction; LUNG injuries; ALVEOLAR macrophages; MACROPHAGE inflammatory proteins; TRYPTOPHAN
- Publication
Inflammation Research, 2023, Vol 72, Issue 8, p1633
- ISSN
1023-3830
- Publication type
Article
- DOI
10.1007/s00011-023-01769-1