Natural molecule Munronoid I attenuates LPS-induced acute lung injury by promoting the K48-linked ubiquitination and degradation of TAK1 - 16/04/21
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Abstract |
Acute lung injury (ALI) is a severe lung disease with limited therapeutic strategies. Munronoid I, a limonoid, which is extracted and purified from Munronia sinica, exhibits effective anti-neoplastic activities. In this study, we attempted to determine the anti-inflammatory effects of Munronoid I using both the lipopolysaccharide (LPS)-induced in vivo murine ALI models and in vitro assays. Our results demonstrated that Munronoid I treatment ameliorated LPS-induced ALI and inflammation in mice. Moreover, it also significantly inhibited LPS-induced pathological injuries, infiltration of inflammatory cells, and production of IL-1β and IL-6. Furthermore, the in vitro assay showed that Munronoid I could inhibit the LPS-induced expression of inflammatory mediators such as iNOS, COX2, and production of pro-inflammatory cytokines by suppressing the activation of NF-κB signaling pathway in mouse peritoneal macrophages. Munronoid I reduced the LPS-, tumor necrosis factor alpha (TNF-α)- or interleukin 1 beta (IL-1β)-induced transforming growth factor beta-activated kinase 1 (TAK1) phosphorylation and protein expression. Furthermore, the Munronoid I also promoted K48-linked ubiquitination and proteasomal degradation of TAK1. Taken together, these results demonstrated that Munronoid I exhibited anti-inflammatory activities both in vitro and in vivo, which might be a potential therapeutic candidate for the treatment of ALI and pulmonary inflammation.
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Highlights |
• | Munronoid I relieves LPS-induced acute lung injury (ALI) in mice. |
• | Munronoid I inhibits LPS-induced inflammatory responses in macrophages. |
• | Munronoid I suppresses LPS-, TNF-α- or IL-1β-induced TAK1 phosphorylation. |
• | Munronoid I promotes the ubiquitination and proteasomal degradation of TAK1. |
Abbreviations : ALI, ARDS, IL-1β, LPS, TLR4, LBP, MD-2, CD14, MyD88, TIR domain, IRAK4, TNF-α, TRAF6, TGF-β, TAK1, TAB, NF-κB, MAPKKK, IL-1R, TNFR1, K63, Itch, Cyld, TMV, DMSO, BALF, iNOS, COX-2, MTT, CHX, MG132, CQ, CETSA, H&E, SFA, TRIF, NEMO, RBCK1, DUB, USP19, P38IP
Keywords : Munronoid I, Inflammation, Acute lung injury, TAK1, Ubiquitination
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Vol 138
Artículo 111543- juin 2021 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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