Macrophage-Derived Exosomes in TLR9-/- Mice Ameliorate Sepsis-Induced Mitochondrial Oxidative Stress and Apoptosis in Cardiomyocytes

Li, Xiang; Luo, Junyu; Li, Yanmei; Lu, Jinping; Li, Yuejin; Ye, Shili; Liu, Lanlan; Yu, Yanxuan; Lu, Yutong; Luan, Yunpeng

doi:10.1155/2022/5719974

Cited by 14 publications

(14 citation statements)

References 40 publications

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“…3E ). The activation of classical JAK2/STAT3 signaling is known to occur during M2 polarization ( 32 ). The present study suggested that CX3CL1 elevated the phosphorylated levels of JAK2 and STAT3 in THP-1-derived macrophage, while incubation with JMS-17-2 almost reversed these ( Fig.…”

Section: Resultsmentioning

confidence: 99%

CX3CL1/CX3CR1 axis alleviates inflammation and apoptosis in human nucleus pulpous cells via M2 macrophage polarization

Gao

Xie

et al. 2023

Exp Ther Med

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CX3C chemokine ligand 1 (CX3CL1) belongs to the CX3C chemokine family and is involved in various disease processes. However, its role in intervertebral disc degeneration (IDD) remains to be elucidated. In the present study, western blotting, reverse transcription-quantitative PCR and ELISA assays were used to assess target gene expression. In addition, immunofluorescence and TUNEL staining were used to assess macrophage infiltration, monocyte migration and apoptosis. The present study aimed to reveal if and how CX3CL1 regulates IDD progression by exploring its effect on macrophage polarization and apoptosis of human nucleus pulposus cells (HNPCs). The data showed that CX3CL1 bound to CX3C motif chemokine receptor 1 (CX3CR1) promoted the M2 phenotype polarization via JAK2/STAT3 signaling, followed by increasing the secretion of anti-inflammatory cytokines from HNPCs. In addition, HNPC-derived CX3CL1 promoted M2 macrophage-derived C-C motif chemokine ligand 17 release thereby reducing the apoptosis of HNPCs. In clinic, the reduction of mRNA and protein levels CX3CL1 in degenerative nucleus pulposus tissues (NPs) was measured. Increased M1 macrophages and pro-inflammatory cytokines were found in NPs of IDD patients with low CX3CL1 expression. Collectively, these findings suggested that the CX3CL1/CX3CR1 axis alleviates IDD by reducing inflammation and apoptosis of HNPCs via macrophages. Therefore, targeting CX3CL1/CX3CR1 axis is expected to produce a new therapeutic approach for IDD.

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Section: Resultsmentioning

confidence: 99%

CX3CL1/CX3CR1 axis alleviates inflammation and apoptosis in human nucleus pulpous cells via M2 macrophage polarization

Gao

Xie

et al. 2023

Exp Ther Med

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“…Oxidative stress contributes to inflammation and organ injury during sepsis ( Kumar et al, 2022 ). Various studies have disclosed that inhibition of oxidative stress ameliorates sepsis and/or sepsis-induced multiple organ dysfunctions, including lung, liver, kidney, heart, etc ( Gong et al, 2022 ; He et al, 2022 ; Li X. et al, 2022 ; Li L. et al, 2022 ). The data of our study revealed that MALT1 overexpression increased the levels of serum proinflammatory cytokines, including TNF-α, IL-6, and IL-1β, while MALT1 knockdown decreased these proinflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 exaggerates multiple organ injury, inflammation, and immune cell imbalance by activating the NF-κB pathway in sepsis

et al. 2023

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ObjectiveMucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) modulates the inflammatory immune response and organ dysfunction, which are closely implicated in sepsis pathogenesis and progression. This study aimed to explore the role of MALT1 in sepsis-induced organ injury, immune cell dysregulation, and inflammatory storms.MethodsSeptic mice were constructed by intraperitoneal injection of lipopolysaccharide, followed by overexpression or knockdown of MALT1 by tail vein injection of the corresponding lentivirus. Mouse naïve CD4+ T cells and bone marrow-derived macrophages were treated with MALT1 overexpression/knockdown lentivirus plus lipopolysaccharide.ResultsIn the lungs, livers, and kidneys of septic mice, MALT1 overexpression exaggerated their injuries, as shown by hematoxylin and eosin staining (all p < 0.05), elevated cell apoptosis, as reflected by the TUNEL assay and cleaved caspase-3 expression (p < 0.05 in the lungs and kidneys), and promoted macrophage infiltration, as illustrated by CD68 immunofluorescence (p < 0.05 in the lungs and kidneys). Meanwhile, in the blood, MALT1 overexpression reduced T-helper (Th)1/Th2 cells, increased Th17/regulatory T-cell ratios (both p < 0.05), promoted systematic inflammation, as revealed by tumor necrosis factor-α, interleukin-6, interleukin-1β, and C-reactive protein (all p < 0.05), elevated oxidative stress, as shown by nitric oxide (p < 0.05), superoxide dismutase, and malondialdehyde (p < 0.05), and enhanced liver and kidney dysfunction, as revealed by an automatic animal biochemistry analyzer (all p < 0.05 except for aspartate aminotransferase). However, MALT1 knockdown exerted the opposite effect as MALT1 overexpression. Ex vivo experiments revealed that MALT1 overexpression promoted the polarization of M1 macrophages and naïve CD4+ T cells toward Th2 and Th17 cells (all p < 0.05), while MALT1 knockdown attenuated these effects (all p < 0.05). Mechanistically, MALT1 positively regulated the nuclear factor-κB (NF-κB) pathway both in vivo and ex vivo (p < 0.05).ConclusionMucosa-associated lymphoid tissue lymphoma translocation protein 1 amplifies multiple organ injury, inflammation, oxidative stress, and imbalance of macrophages and CD4+ T cells by activating the NF-κB pathway in sepsis.

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“…This is significant because immune-inflammatory cells communicate some aspects with MSCs-derived exosomes. 5 Natural sweroside, a Chinese traditional medicinal compound extracted from Swertia pseudochinensis Hara's plant, which said to have potent antioxidant, anti-inflammatory, anti-bacterial, anti-fungal, anti-diabetic, and hepatoprotective properties. 17,18 According to previous research, pre-treatment with sweroside prevented cardiomyocyte oxidative stress and intercellular ROS generation caused by aconitine.…”

Section: Introductionmentioning

confidence: 99%

“…4 According to previous reports, excessive inflammation, mitochondrial dysfunction, an imbalance of oxidants and antioxidants, increased apoptosis, and problems with the autonomic nervous system all contributed to sepsis-induced heart damage. 5 The myocardial injury and dysfunction after sepsis have been significantly lowered left ventricular ejection fraction, impaired myocardial contractility, and transient biventricular dilation in patients. Therefore, it is essential to find a specific biochemical process and mechanisms of SMI in order to create new therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

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Sweroside functionalized with Mesenchymal Stem cells derived exosomes attenuates sepsis-induced myocardial injury by modulating oxidative stress and apoptosis in rats

Wang

et al. 2023

J Biomater Appl

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Sepsis is a life-threatening problem by organ dysfunction influenced by negative inflammatory responses and stimulated oxidative stress, which most of sepsis patients about 40–60% are accompanied with myocardial injury. Recently, stem cells derived exosomes could effectively apply in the numerous diseases by combined with natural therapeutic agents. In the present investigation, Sweroside functionalized with exosomes to control inflammatory responses by sepsis and significantly proved the function of depreciated myocardial injury-induced by LPS. The sweroside could have effectively delivered to cardiomyocytes cells via exosome carriers. The induced-SMI rats exhibited severe myocardial injury and apoptosis by in vivo experiments and treatment of sweroside-functionalized exosomes (SWO/EX) reassured the phenotypes. Importantly, SWO/EX significantly downregulated the ROS generation in the SMI rat models. The SOD and GSH activity were also suppressed in SMI rat models, and treated models with SWO/EXO could have effective liberating activity in the Rats. Meanwhile, SWO/EXO treated LPS-induced cardiomyocytes displayed that significant reduction of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) levels and also increasing cell survival and prevented apoptosis. Thus, we demonstrate that MS-cells derived exosome with sweroside could have effectively impede sepsis-induced myocardial injury. SWO/EX formulations might be applied as a potent therapeutic agent for SMI therapy.

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Macrophage-Derived Exosomes in TLR9-/- Mice Ameliorate Sepsis-Induced Mitochondrial Oxidative Stress and Apoptosis in Cardiomyocytes

Cited by 14 publications

References 40 publications

CX3CL1/CX3CR1 axis alleviates inflammation and apoptosis in human nucleus pulpous cells via M2 macrophage polarization

CX3CL1/CX3CR1 axis alleviates inflammation and apoptosis in human nucleus pulpous cells via M2 macrophage polarization

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 exaggerates multiple organ injury, inflammation, and immune cell imbalance by activating the NF-κB pathway in sepsis

Sweroside functionalized with Mesenchymal Stem cells derived exosomes attenuates sepsis-induced myocardial injury by modulating oxidative stress and apoptosis in rats

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