HO-1/autophagic flux axis alleviated sepsis-induced acute lung injury via inhibiting NLRP3 inflammasome

Li, Shutong; Jiang, Yu; Wang, Jia; Huafei, Deng; Yan, Shifan; Huili, Wen; Lianhong, Zou; Liu, Xiehong; Liu, Yanjuan; Chen, Fang

doi:10.1016/j.cellsig.2022.110473

Cited by 10 publications

(3 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is worth noting that sepsis is one of the causes of ALI/ARDS. Li et al found that Heme oxygenase-1 (HO-1) mitigated the inflammatory response in sepsis-induced ALI by activating the autophagy flux axis and inhibiting the NLRP3 inflammasome [ 23 ]. Although P62-mediated autophagy is implicated in ALI, its exact molecular mechanism remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Myeloid-specific Hdac10 deletion protects against LPS-induced acute lung injury via P62 acetylation at lysine 165

Xiang,

Zhong,

Lai

et al. 2024

Respir Res

View full text Add to dashboard Cite

Background Aberrant activation of macrophages is associated with pathogenesis of acute lung injury (ALI). However, the potential pathogenesis has not been explored. Objectives We aimed to identify whether histone deacetylase (HDAC) 10 is involved in lipopolysaccharide (LPS)-exposed ALI and reveal the underlying pathogenesis by which it promotes lung inflammation in LPS-exposed ALI via modifying P62 with deacetylation. Methods We constructed an ALI mice model stimulated with LPS to determine the positive effect of Hdac10 deficiency. Moreover, we cultured murine alveolar macrophage cell line (MH-S cells) and primary bone marrow-derived macrophages (BMDMs) to explore the pro-inflammatory activity and mechanism of HDAC10 after LPS challenge. Results HDAC10 expression was increased both in mice lung tissues and macrophage cell lines and promoted inflammatory cytokines production exposed to LPS. Hdac10 deficiency inhibited autophagy and inflammatory response after LPS stimulation. In vivo, Hdac10fl/fl-LysMCre mice considerably attenuated lung inflammation and inflammatory cytokines release exposed to LPS. Mechanistically, HDAC10 interacts with P62 and mediates P62 deacetylation at lysine 165 (K165), by which it promotes P62 expression and increases inflammatory cytokines production. Importantly, we identified that Salvianolic acid B (SAB), an HDAC10 inhibitor, reduces lung inflammatory response in LPS-stimulated ALI. Conclusion These results uncover a previously unknown role for HDAC10 in regulating P62 deacetylation and aggravating lung inflammation in LPS-induced ALI, implicating that targeting HDAC10 is an effective therapy for LPS-exposed ALI.

show abstract

Section: Discussionmentioning

confidence: 99%

Myeloid-specific Hdac10 deletion protects against LPS-induced acute lung injury via P62 acetylation at lysine 165

Xiang,

Zhong,

Lai

et al. 2024

Respir Res

View full text Add to dashboard Cite

show abstract

“…[27] In addition, excessive uncontrolled apoptosis and oxidative stress are characteristics of ALI, and lavender oil pretreatment can protect rats from sepsis-induced ALI by inactivating the NF-κB pathway. [28,29] Shutong et al [30] showed that sepsis-induced ALI can be alleviated by HO-1 autophagic flux through inhibition of the NLRP3 inflammasome. In addition, it has been reported that fine particulate matter in urban air can inhibit cell activity by activating the AMPK-Beclin1 pathway in ALI to induce ferroptosis.…”

Section: Tempol Affects Gsh Synthesis Through Nrf2 Inhibits Ferroptos...mentioning

confidence: 99%

Tempol alleviates acute lung injury by affecting glutathione synthesis through Nrf2 and inhibiting ferroptosis in lung epithelial cells

Ai,

Li,

Wang

et al. 2024

J Biochem & Molecular Tox

View full text Add to dashboard Cite

As a life‐threatening disease, acute lung injury (ALI) may progress to chronic pulmonary fibrosis. For the treatment of lung injury, Tempol is a superoxide dismutase mimetic and intracellular redox agent that can be a potential drug. This study investigated the regulatory mechanism of Tempol in the treatment of ALI. A mouse model of ALI was established, and HE staining was used to examine histomorphology. The CCK‐8 assay was used to measure cell viability, and oxidative stress was assessed by corresponding kits. Flow cytometry and dichlorodihydrofluorescein diacetate staining assays were used to detect reactive oxygen species (ROS) levels. Protein expression levels were measured by Western blot analysis and ELISA. Pulmonary vascular permeability was used to measure the lung wet/dry weight ratio. The level of oxidative stress was increased in ALI mice, and the level of ferroptosis was upregulated. Tempol inhibited this effect and alleviated ALI. The administration of Tempol alleviated the pathological changes in ALI, inhibited pulmonary vascular permeability, and improved lung injury in ALI mice. The upregulation of genes essential for glutathione (GSH) metabolism induced by lipopolysaccharide (LPS) was inhibited by Tempol. In addition, nuclear factor‐related factor 2 (Nrf2) is activated by Tempol therapy to regulate the de novo synthesis pathway of GSH, thereby alleviating LPS‐induced lung epithelial cell damage. The results showed that Tempol alleviated ALI by activating the Nrf2 pathway to inhibit oxidative stress and ferroptosis in lung epithelial cells. In conclusion, this study demonstrates that Tempol alleviates ALI by inhibiting ferroptosis in lung epithelial cells through the effect of Nrf2 on GSH synthesis.

show abstract

“…Autophagy modulation further proved promising for reducing acute lung injury in models of sepsis, ARDS, or lung fibrosis [30]. Autophagy activation has been implicated in lung protection by heme-oxygenase-1 or hydrogen sulfide in CLP-induced sepsis, where autophagy activation attenuated acute lung injury and autophagy inhibition showed the opposite effect [31 ▪ ,32 ▪ ]. Likewise, protection by aspirin against lung fibrosis in mice appeared mediated via autophagy activation, as it was abrogated by autophagy inhibition [33].…”

Section: Autophagy In Critical Illnessmentioning

confidence: 99%

Nutrition and autophagy deficiency in critical illness

Vanhorebeek

Casaer

Gunst

2023

Current Opinion in Critical Care

View full text Add to dashboard Cite

Purpose of review Critical illness imposes a severe insult on the body, with various stressors triggering pronounced cell damage. This compromises cellular function, leading to a high risk of multiple organ failure. Autophagy can remove damaged molecules and organelles but appears insufficiently activated during critical illness. This review discusses insight into the role of autophagy in critical illness and the involvement of artificial feeding in insufficient autophagy activation in critical illness. Recent findings Animal studies manipulating autophagy have shown its protective effects against kidney, lung, liver, and intestinal injury after several critical insults. Autophagy activation also protected peripheral, respiratory, and cardiac muscle function, despite aggravated muscle atrophy. Its role in acute brain injury is more equivocal. Animal and patient studies showed that artificial feeding suppressed autophagy activation in critical illness, particularly with high protein/amino acid doses. Feeding-suppressed autophagy may explain short and long-term harm by early enhanced calorie/protein feeding in large randomized controlled trials. Summary Insufficient autophagy during critical illness is at least partly explained by feeding-induced suppression. This may explain why early enhanced nutrition failed to benefit critically ill patients or even induced harm. Safe, specific activation of autophagy avoiding prolonged starvation opens perspectives for improving outcomes of critical illness.

show abstract

HO-1/autophagic flux axis alleviated sepsis-induced acute lung injury via inhibiting NLRP3 inflammasome

Cited by 10 publications

References 47 publications

Myeloid-specific Hdac10 deletion protects against LPS-induced acute lung injury via P62 acetylation at lysine 165

Myeloid-specific Hdac10 deletion protects against LPS-induced acute lung injury via P62 acetylation at lysine 165

Tempol alleviates acute lung injury by affecting glutathione synthesis through Nrf2 and inhibiting ferroptosis in lung epithelial cells

Nutrition and autophagy deficiency in critical illness

Contact Info

Product

Resources

About