Systemic inflammatory response syndrome is triggered by mitochondrial damage (Review)

Kong, Can; Song, Wei; Fu, Tao

doi:10.3892/mmr.2022.12663

Cited by 25 publications

(19 citation statements)

References 83 publications

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“…When released into the cytosol, mtDNA activates the NLRP3 inflammasome further enhancing the production of pro-inflammatory cytokines, and once secreted into extracellular plasma enhances systemic inflammation. 28 The overall inflammation, in turn, promotes mtROS accumulation causing the development of a vicious cycle centered around the continuance of mitochondrial dysfunction. 29 Further, such sustained production of mtROS, and thus sustenance of a pro-inflammatory environment, can affect intra-organelle crosstalk potentially leading to the development of autoimmunity.…”

Section: Aberrant Oxphos Drives An Inflammatory Phenotypementioning

confidence: 99%

Mitochondrial bioenergetic changes in systemic lupus erythematosus immune cell subsets: Contributions to pathogenesis and clinical applications

Yennemadi

Keane

Leisching

2023

Lupus

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The association of dysregulated metabolism in systemic lupus erythematosus (SLE) pathogenesis has prompted investigations into metabolic rewiring and the involvement of mitochondrial metabolism as a driver of disease through NLRP3 inflammasome activation, disruption of mitochondrial DNA maintenance, and pro-inflammatory cytokine release. The use of Agilent Seahorse Technology to gain functional in situ metabolic insights of selected cell types from SLE patients has identified key parameters that are dysregulated during disease. Mitochondrial functional assessments specifically can detect dysfunction through oxygen consumption rate (OCR), spare respiratory capacity, and maximal respiration measurements, which, when coupled with disease activity scores could show potential as markers of disease activity. CD4+ and CD8 + T cells have been assessed in this way and show that oxygen consumption rate, spare respiratory capacity, and maximal respiration are blunted in CD8 + T cells, with results not being as clear cut in CD4 + T cells. Additionally, glutamine, processed by mitochondrial substrate level phosphorylation is emerging as a key role player in the expansion and differentiation of Th1, Th17, ϒδ T cells, and plasmablasts. The role that circulating leukocytes play in acting as bioenergetic biomarkers of diseases such as diabetes suggests that this may also be a tool to detect preclinical SLE. Therefore, the metabolic characterization of immune cell subsets and the collection of metabolic data during interventions is also essential. The delineation of the metabolic tuning of immune cells in this way could lead to novel strategies in treating metabolically demanding processes characteristic of autoimmune diseases such as SLE.

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Section: Aberrant Oxphos Drives An Inflammatory Phenotypementioning

confidence: 99%

Mitochondrial bioenergetic changes in systemic lupus erythematosus immune cell subsets: Contributions to pathogenesis and clinical applications

Yennemadi

Keane

Leisching

2023

Lupus

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“…The release of proinflammatory cytokines IL-6, IL-8, and IL-1β from monocytes is also mediated by the release of mtDAMPs ( Figure 1 ). The inflammatory response mediated by excessive mtDAMPs leads to MODS and poor clinical outcomes [ 42 – 44 ]. Since mtDAMPs play a critical role in SIRS, mtDAMPs may be used as biomarkers to evaluate the trauma severity and decide on treatment strategies.…”

Section: Damps Sirs and Traumamentioning

confidence: 99%

Translational and Clinical Significance of DAMPs, PAMPs, and PRRs in Trauma-induced Inflammation

Rai¹,

Mathews²,

Agrawal³

2022

Arch Clin Biomed Res

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Increased morbidity and mortality after polytrauma due to multiple organ failure (MOF) is a major concern for clinicians. Systemic inflammatory response syndrome (SIRS) and sepsis are the major underlying causes. Damage-associated molecular proteins (DAMPs) released after polytrauma induce an inflammatory immune response to repair the tissue, however, persistent inflammation finally results in immunosuppression and MOF. During immunosuppression, additional exposure of the traumatized tissue to pattern-associated molecular patterns (PAMPs) further adds to the continuum of inflammatory cascade causing sepsis. These two hits worsen the condition of the patient and increase morbidity and mortality. Thus, it is critical to stratify the patient based on trauma severity and inflammatory biomarkers levels and design treatment accordingly for a better clinical outcome. Although some of the molecular mechanisms involved in SIRS and MOF after polytrauma have been reported, there is limited information on the critical factors related to the study of DAMPs and PAMPs, including the timing of sampling (time elapsed after trauma), source of sampling (blood, urine, saliva), proteomics and metabolomics, multiplex plasma assay, comparative interpretation of the results from various sources and diagnostic value, and interpretation on the translational and clinical significance. Additionally, there is limited literature on DAMPs like heat shock proteins, mitochondrial DNA, neutrophil extracellular traps, and their role in SIRS and MOF. Further, it is also important to distinguish between the biomarkers of SIRS and sepsis in a time-bound window to have a better clinical outcome. This critical review focuses on these aspects to provide comprehensive information and thought-provoking discussion to design future investigation and clinical trials.

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“…Mitochondria are important organelles involved in energy metabolism ( 43 ). ATP produced by mitochondria cannot maintain the energy balance of neurocytes during ischemia and hypoxia after stroke, resulting in cell death ( 44 ).…”

Section: Molecular Pathological Hallmarks Of Ischemic Strokementioning

confidence: 99%

Venous stroke–a stroke subtype that should not be ignored

et al. 2022

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Based on the etiology, stroke can be classified into ischemic or hemorrhagic subtypes, which ranks second among the leading causes of death. Stroke is caused not only by arterial thrombosis but also by cerebral venous thrombosis. Arterial stroke is currently the main subtype of stroke, and research on this type has gradually improved. Venous thrombosis, the particular type, accounts for 0.5–1% of all strokes. Due to the lack of a full understanding of venous thrombosis, as well as its diverse clinical manifestations and neuroimaging features, there are often delays in admission for it, and it is easy to misdiagnose. The purpose of this study was to review the pathophysiology mechanisms and clinical features of arterial and venous thrombosis and to provide guidance for further research on the pathophysiological mechanism, clinical diagnosis, and treatment of venous thrombosis. This review summarizes the pathophysiological mechanisms, etiology, epidemiology, symptomatology, diagnosis, and treatment heterogeneity of venous thrombosis and compares it with arterial stroke. The aim is to provide a reference for a comprehensive understanding of venous thrombosis and a scientific understanding of various pathophysiological mechanisms and clinical features related to venous thrombosis, which will contribute to understanding the pathogenesis of intravenous stroke and provide insight into diagnosis, treatment, and prevention.

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Systemic inflammatory response syndrome is triggered by mitochondrial damage (Review)

Cited by 25 publications

References 83 publications

Mitochondrial bioenergetic changes in systemic lupus erythematosus immune cell subsets: Contributions to pathogenesis and clinical applications

Mitochondrial bioenergetic changes in systemic lupus erythematosus immune cell subsets: Contributions to pathogenesis and clinical applications

Translational and Clinical Significance of DAMPs, PAMPs, and PRRs in Trauma-induced Inflammation

Venous stroke–a stroke subtype that should not be ignored

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