The role of mitophagy in pulmonary sepsis

Mohsin, Mohd; Tabassum, Gulnaz; Ahmad, Shaniya; Ali, Shakir; Syed, Mansoor Ali

doi:10.1016/j.mito.2021.04.009

Cited by 25 publications

(9 citation statements)

References 133 publications

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“…Other mechanisms may underlie the protective effects of HG in ALI rats, which require an in-depth exploration. Reactive oxygen species (ROS)-mediated NLRP3 inflammasome activation has been reported to play a role in the pathogenesis of septic ALI [ 58 ] [PMID: 33,894,359]. The changes of relevant indicators of oxidative stress (SOD, MDA, GSH) in the present study might be associated with increased formation ROS.…”

Section: Discussionmentioning

confidence: 56%

Suppression of NOD-like receptor protein 3 inflammasome activation and macrophage M1 polarization by hederagenin contributes to attenuation of sepsis-induced acute lung injury in rats

Wang

Zhao

2022

Bioengineered

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Acute lung injury (ALI) is a major leading cause of death in sepsis patients. Hederagenin (HG), derived from Hedera helix Linné , has anti-inflammatory effects, while its role in sepsis-induced ALI has not been elucidated. In vivo , rats were subjected to cecal ligation and puncture to induce ALI and then treated with HG (12.5, 25, or 50 mg/kg) by gavage. Administration of HG raised survival rate, ameliorated lung injury, and decreased lung wet/dry ratio and inflammatory cell accumulation in bronchoalveloar lavage fluid (BALF) of ALI rats. HG inhibited macrophage polarization toward the M1 phenotype as evidenced by decreased CD86 expression in rat lung tissues. Moreover, HG decreased the secretion of TNF-α, IL-6 and monocyte chemoattractant protein-1 (MCP-1) in BALF and the levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung tissues. In vitro , phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 macrophages were stimulated with 100 ng/mL lipopolysaccharide. HG treatment inhibited M1 macrophage polarization and the production of M1-related pro-inflammatory mediators (IL-6, MCP-1, iNOS, and COX-2). Mechanistically, HG inhibited NLRP3 inflammasome activation and subsequent release of IL-18 and IL-1β, and suppressed NF-κB signaling pathway both in vivo and in vitro . Notably, HG treatment further emphasized the inhibitory effect of NF-κB inhibitor BAY11-7082 on NLRP3 inflammasome activation and macrophage M1 polarization. Taken together, HG exerts a protective effect against sepsis-induced ALI by reducing the inflammatory response and macrophage M1 polarization, which may involve NF-κB pathway-modulated NLRP3 inflammasome activation.

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Section: Discussionmentioning

confidence: 56%

Suppression of NOD-like receptor protein 3 inflammasome activation and macrophage M1 polarization by hederagenin contributes to attenuation of sepsis-induced acute lung injury in rats

Wang

Zhao

2022

Bioengineered

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“…Other reports and our study show that KP-induced pyroptosis requires NLRP3 inflammasome [ 11 ]. Mitophagy, which is the selective autophagy of mitochondria that removes unwanted or damaged mitochondria, is considered a key factor in the negative regulation of NLRP3 inflammasome activation [ 47 ]. In models related to inflammation such as alcoholic liver disease and high-fat diet, previous studies demonstrated that anthocyanins could inhibit NLRP3 inflammasome activation [ 48 , 49 ], but the role of mitophagy of immune cells was not discussed.…”

Section: Discussionmentioning

confidence: 99%

Anthocyanin Extract from Purple Sweet Potato Exacerbate Mitophagy to Ameliorate Pyroptosis in Klebsiella pneumoniae Infection

Dong

Wang

et al. 2021

IJMS

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Given the rise of morbidity and mortality caused by Klebsiella pneumoniae (KP), the increasing number of strains resistant to antibiotics, and the emergence of hypervirulent Klebsiella pneumonia, treatment of KP infection becomes difficult; thus, novel drugs are necessary for treatment. Anthocyanins, or natural flavonoids, have an extensive effect against bacterial infection. However, few studies on anti-KP are identified. Here, we evaluated the therapeutic effect of purple sweet potato anthocyanins (PSPAs) on KP, containing 98.7% delphinidin 3-sambubioside. Results showed that KP-infected mice after PSPAs treatment manifested decreased mortality, weakened lung injury, dampened inflammatory responses, and reduced bacterial systemic dissemination in vivo. In Vitro, PSPAs significantly suppressed pyroptosis and restricted NLRP3 inflammasome activation in alveolar macrophages infected with KP. As for the mechanism, PSPAs promote mitophagy by recruiting Parkin to the mitochondria. PSPAs-conferred mitophagy increased mitochondrial membrane potential and decreased mitochondrial reactive oxygen species and mitochondrial DNA, resulting in impaired NLRP3 inflammasome activation. In addition, the promotion of mitophagy by PSPAs required the Nrf2 signaling pathway. Collectively, these findings suggest that PSPAs are a potential option for the treatment of KP infection.

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“…Mitophagy is a form of macrophagy, or selective autophagy, of damaged mitochondria ( Mohsin et al, 2021 ). It is usually divided into ubiquitin-dependent and nondependent pathways.…”

Section: Mitochondrial Dynamics and Mitophagymentioning

confidence: 99%

Mitochondrial DNA Release Contributes to Intestinal Ischemia/Reperfusion Injury

et al. 2022

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Mitochondria release many damage-associated molecular patterns (DAMPs) when cells are damaged or stressed, with mitochondrial DNA (mtDNA) being. MtDNA activates innate immune responses and induces inflammation through the TLR-9, NLRP3 inflammasome, and cGAS-STING signaling pathways. Released inflammatory factors cause damage to intestinal barrier function. Many bacteria and endotoxins migrate to the circulatory system and lymphatic system, leading to systemic inflammatory response syndrome (SIRS) and even damaging the function of multiple organs throughout the body. This process may ultimately lead to multiple organ dysfunction syndrome (MODS). Recent studies have shown that various factors, such as the release of mtDNA and the massive infiltration of inflammatory factors, can cause intestinal ischemia/reperfusion (I/R) injury. This destroys intestinal barrier function, induces an inflammatory storm, leads to SIRS, increases the vulnerability of organs, and develops into MODS. Mitophagy eliminates dysfunctional mitochondria to maintain cellular homeostasis. This review discusses mtDNA release during the pathogenesis of intestinal I/R and summarizes methods for the prevention or treatment of intestinal I/R. We also discuss the effects of inflammation and increased intestinal barrier permeability on drugs.

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The role of mitophagy in pulmonary sepsis

Cited by 25 publications

References 133 publications

Suppression of NOD-like receptor protein 3 inflammasome activation and macrophage M1 polarization by hederagenin contributes to attenuation of sepsis-induced acute lung injury in rats

Suppression of NOD-like receptor protein 3 inflammasome activation and macrophage M1 polarization by hederagenin contributes to attenuation of sepsis-induced acute lung injury in rats

Anthocyanin Extract from Purple Sweet Potato Exacerbate Mitophagy to Ameliorate Pyroptosis in Klebsiella pneumoniae Infection

Mitochondrial DNA Release Contributes to Intestinal Ischemia/Reperfusion Injury

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