Experimental lung research · 2026
IL-36G drives sepsis-induced lung injury via NF-κB-dependent activation of the NLRP3 inflammasome in macrophage pyroptosis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Yan Mingguo, Chen Zhixin, Song Yuan, Yuan Zheng
Аннотация
BACKGROUND: Sepsis is a critical illness marked by widespread inflammation and failure of multiple organs. Pyroptosis and NLRP3 inflammasome activation play critical roles in sepsis pathogenesis. However, the involvement of interleukin-36 gamma (IL-36G) in this process remains unclear. This work probe to clarify the role and mechanism of IL-36G in sepsis-induced inflammation and lung injury.
METHODS: RAW264.7 macrophages were exposed to lipopolysaccharide (LPS) to construct an in vitro model of sepsis. Cell viability, pyroptosis, and inflammatory cytokine expression were assessed by CCK-8 assay, flow cytometry, qPCR, and Western blot. The NF-κB pathway and NLRP3 inflammasome activation were evaluated following IL-36G overexpression or knockdown, with or without the NF-κB inhibitor BAY 11-7085. In vivo, a cecal ligation and puncture (CLP)-induced sepsis model was used in IL-36G knockout mice to assess lung injury and inflammatory responses.
RESULTS: LPS stimulation induced pyroptosis and upregulated IL-36G expression in RAW264.7 cells, accompanied by increased levels of IL-6, IL-1β, TNF-α, and IL-18. IL-36G knockdown attenuated LPS-induced pyroptosis, inflammatory cytokine production, and expression of pyroptosis-related proteins. IL-36G overexpression activated the NF-κB pathway and enhanced NLRP3 inflammasome activation, while BAY 11-7085 inhibited these effects. In CLP-induced septic mice, IL-36G expression was upregulated, and its knockout improved survival, reduced the lung wet/dry (W/D) weight ratio, alleviated lung tissue damage, reduced inflammatory cytokine levels, and suppressed NF-κB-mediated NLRP3 inflammasome activation.
CONCLUSION: IL-36G promoted pyroptosis and NLRP3 inflammasome activation via NF-κB signaling pathway, contributing to sepsis-induced lung injury. Knockdown of IL-36G mitigated inflammation and tissue damage, indicating the therapeutic potential of IL-36G in sepsis.
METHODS: RAW264.7 macrophages were exposed to lipopolysaccharide (LPS) to construct an in vitro model of sepsis. Cell viability, pyroptosis, and inflammatory cytokine expression were assessed by CCK-8 assay, flow cytometry, qPCR, and Western blot. The NF-κB pathway and NLRP3 inflammasome activation were evaluated following IL-36G overexpression or knockdown, with or without the NF-κB inhibitor BAY 11-7085. In vivo, a cecal ligation and puncture (CLP)-induced sepsis model was used in IL-36G knockout mice to assess lung injury and inflammatory responses.
RESULTS: LPS stimulation induced pyroptosis and upregulated IL-36G expression in RAW264.7 cells, accompanied by increased levels of IL-6, IL-1β, TNF-α, and IL-18. IL-36G knockdown attenuated LPS-induced pyroptosis, inflammatory cytokine production, and expression of pyroptosis-related proteins. IL-36G overexpression activated the NF-κB pathway and enhanced NLRP3 inflammasome activation, while BAY 11-7085 inhibited these effects. In CLP-induced septic mice, IL-36G expression was upregulated, and its knockout improved survival, reduced the lung wet/dry (W/D) weight ratio, alleviated lung tissue damage, reduced inflammatory cytokine levels, and suppressed NF-κB-mediated NLRP3 inflammasome activation.
CONCLUSION: IL-36G promoted pyroptosis and NLRP3 inflammasome activation via NF-κB signaling pathway, contributing to sepsis-induced lung injury. Knockdown of IL-36G mitigated inflammation and tissue damage, indicating the therapeutic potential of IL-36G in sepsis.