Decreased Circulating mtDNA Levels in Professional Male Volleyball Players

2016 ◽  
Vol 11 (1) ◽  
pp. 116-121 ◽  
Author(s):  
Milena Nasi ◽  
Alessandro Cristani ◽  
Marcello Pinti ◽  
Igor Lamberti ◽  
Lara Gibellini ◽  
...  
Keyword(s):  
High Plasma ◽  
Sterile Inflammation ◽  
Clinical Parameters ◽  
Anthropometric Parameters ◽  
Inflammatory Conditions ◽  
Volleyball Players ◽  
Anti Inflammatory ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Inflammatory Effect

Purpose:Exercise exerts various effects on the immune system, and evidence is emerging on its anti-inflammatory effects; the mechanisms on the basis of these modifications are poorly understood. Mitochondrial DNA (mtDNA) released from damaged cells acts as a molecule containing the so-called damage-associated molecular patterns and can trigger sterile inflammation. Indeed, high plasma levels of mtDNA are associated to several inflammatory conditions and physiological aging and longevity. The authors evaluated plasma mtDNA in professional male volleyball players during seasonal training and the possible correlation between mtDNA levels and clinical parameters, body composition, and physical performance.Methods:Plasma mtDNA was quantified by real-time PCR every 2 mo in 12 professional volleyball players (PVPs) during 2 consecutive seasons. As comparison, 20 healthy nonathlete male volunteers (NAs) were analyzed.Results:The authors found lower levels of mtDNA in plasma of PVPs than in NAs. However, PVPs showed a decrease of circulating mtDNA only in the first season, while no appreciable variations were observed during the second season. No correlation was observed among mtDNA, hematochemical, and anthropometric parameters.Conclusions:Regular physical activity appeared associated with lower levels of circulating mtDNA, further confirming the protective, anti-inflammatory effect of exercise.

scholarly journals Selective packaging of mitochondrial proteins into extracellular vesicles prevents the release of mitochondrial DAMPs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kiran Todkar ◽  
Lilia Chikhi ◽  
Véronique Desjardins ◽  
Firas El-Mortada ◽  
Geneviève Pépin ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mitochondrial Proteins ◽  
Control Mechanisms ◽  
Mitochondrial Content ◽  
Sorting Nexin ◽  
Inflammatory Conditions ◽  
Selective Targeting ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Insight Into

AbstractMost cells constitutively secrete mitochondrial DNA and proteins in extracellular vesicles (EVs). While EVs are small vesicles that transfer material between cells, Mitochondria-Derived Vesicles (MDVs) carry material specifically between mitochondria and other organelles. Mitochondrial content can enhance inflammation under pro-inflammatory conditions, though its role in the absence of inflammation remains elusive. Here, we demonstrate that cells actively prevent the packaging of pro-inflammatory, oxidized mitochondrial proteins that would act as damage-associated molecular patterns (DAMPs) into EVs. Importantly, we find that the distinction between material to be included into EVs and damaged mitochondrial content to be excluded is dependent on selective targeting to one of two distinct MDV pathways. We show that Optic Atrophy 1 (OPA1) and sorting nexin 9 (Snx9)-dependent MDVs are required to target mitochondrial proteins to EVs, while the Parkinson’s disease-related protein Parkin blocks this process by directing damaged mitochondrial content to lysosomes. Our results provide insight into the interplay between mitochondrial quality control mechanisms and mitochondria-driven immune responses.

scholarly journals Immunopathogenesis of Acute Kidney Injury

2018 ◽  
Vol 46 (8) ◽  
pp. 930-943 ◽  
Author(s):  
Zaher A. Radi
Keyword(s):  
Acute Kidney Injury ◽  
T Cells ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Drug Induced ◽  
Inflammatory Damage ◽  
Anti Inflammatory ◽  
Renal Tubular ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Pathophysiologically, the classification of acute kidney injury (AKI) can be divided into three categories: (1) prerenal, (2) intrinsic, and (3) postrenal. Emerging evidence supports the involvement of renal tubular epithelial cells and the innate and adaptive arms of the immune system in the pathogenesis of intrinsic AKI. Pro-inflammatory damage-associated molecular patterns, pathogen-associated molecular patterns, hypoxia inducible factors, toll-like receptors, complement system, oxidative stress, adhesion molecules, cell death, resident renal dendritic cells, neutrophils, T and B lymphocytes, macrophages, natural killer T cells, cytokines, and secreted chemokines contribute to the immunopathogenesis of AKI. However, other immune cells and pathways such as M2 macrophages, regulatory T cells, progranulin, and autophagy exhibit anti-inflammatory properties and facilitate kidney tissue repair after AKI. Thus, therapies for AKI include agents such as anti-inflammatory (e.g., recombinant alkaline phosphatase), antioxidants (iron chelators), and apoptosis inhibitors. In preclinical toxicity studies, drug-induced kidney injury can be seen after exposure to a nephrotoxicant test article due to immune mechanisms and dysregulation of innate, and/or adaptive cellular immunity. The focus of this review will be on intrinsic AKI, as it relates to the immune and renal systems cross talks focusing on the cellular and pathophysiologic mechanisms of AKI.

scholarly journals Different DOACs Control Inflammation in Cardiac Ischemia-Reperfusion Differently

2020 ◽  
Author(s):  
Ihsan Gadi ◽  
Sameen Fatima ◽  
Ahmed Elwakiel ◽  
Sumra Nazir ◽  
Mohd Mohanad Al-Dabet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Sterile Inflammation ◽  
Inflammasome Activation ◽  
Differential Effects ◽  
Anti Inflammatory ◽  
Anticoagulant Function ◽  
Inflammatory Effect

Rationale: While thrombin is the key protease in thrombus formation, other coagulation proteases, such as fXa or activated protein C (aPC), independently modulate intracellular signaling via partially distinct receptors. Objective: To study the differential effects of fXa or fIIa inhibition on gene expression and inflammation in myocardial ischemia-reperfusion injury (IRI). Methods and Results: Mice were treated with a direct fIIa inhibitor (fIIai) or direct fXa inhibitor (fXai) at doses that induced comparable anticoagulant effects ex vivo and in vivo (tail bleeding assay and FeCl3-induced thrombosis). Myocardial IRI was induced via LAD ligation. We determined infarct size and in vivo aPC generation, analyzed gene expression by RNAseq, and performed immunoblotting and ELISA. The signaling-only 3K3A-aPC variant and inhibitory antibodies that blocked all or only the anticoagulant function of aPC were used to determine the role of aPC. Doses of fIIai and fXai that induced comparable anticoagulant effects resulted in a comparable reduction in infarct size. However, unbiased gene expression analyses revealed marked differences, including pathways related to sterile inflammation and inflammasome regulation. fXai but not fIIai inhibited sterile inflammation by reducing the expression of proinflammatory cytokines (IL-1beta, IL-6, and TNFalpha) as well as NF-κB and inflammasome activation. This anti-inflammatory effect was associated with reduced myocardial fibrosis 28 days post myocardial IRI. Mechanistically, in vivo aPC generation was higher with fXai than with fIIai. Inhibition of the anticoagulant and signaling properties of aPC abolished the anti-inflammatory effect associated with fXai, while inhibiting only the anticoagulant function of aPC had no effect. Combining 3K3A-aPC with fIIai reduced the inflammatory response, mimicking the fXai-associated effect. Conclusions: We showed that specific inhibition of coagulation via DOACs had differential effects on gene expression and inflammation, despite comparable anticoagulant effects and infarct sizes. Targeting individual coagulation proteases induces specific cellular responses unrelated to their anticoagulant effect.

DAMPs, PAMPs, and LAMPs in Immunity and Sterile Inflammation

2020 ◽  
Vol 15 (1) ◽  
pp. 493-518 ◽  
Author(s):  
Joel Zindel ◽  
Paul Kubes
Keyword(s):  
Immune Cell ◽  
Inflammatory Diseases ◽  
Sterile Inflammation ◽  
Lifestyle Choices ◽  
Inflammatory Site ◽  
Specific Receptors ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Killer T Cells ◽  
Invariant Natural Killer

Recognizing the importance of leukocyte trafficking in inflammation led to some therapeutic breakthroughs. However, many inflammatory pathologies remain without specific therapy. This review discusses leukocytes in the context of sterile inflammation, a process caused by sterile (non-microbial) molecules, comprising damage-associated molecular patterns (DAMPs). DAMPs bind specific receptors to activate inflammation and start a highly optimized sequence of immune cell recruitment of neutrophils and monocytes to initiate effective tissue repair. When DAMPs are cleared, the recruited leukocytes change from a proinflammatory to a reparative program, a switch that is locally supervised by invariant natural killer T cells. In addition, neutrophils exit the inflammatory site and reverse transmigrate back to the bloodstream. Inflammation persists when the program switch or reverse transmigration fails, or when the coordinated leukocyte effort cannot clear the immunostimulatory molecules. The latter causes inappropriate leukocyte activation, a driver of many pathologies associated with poor lifestyle choices. We discuss lifestyle-associated inflammatory diseases and their corresponding immunostimulatory lifestyle-associated molecular patterns (LAMPs) and distinguish them from DAMPs.

scholarly journals Effects of aqueous and ethanolic extracts of Aegle marmelos (BAEL) leaves on chronic inflammation in rats

2016 ◽  
Vol 9 (2) ◽  
pp. 52-54
Author(s):  
Sharmin Rahman ◽  
Eliza Omar Eva ◽  
Rezaul Quader ◽  
Muqbula Tasrin ◽  
Md Ismail Khan
Keyword(s):  
Chronic Inflammation ◽  
Granuloma Formation ◽  
Aegle Marmelos ◽  
Inflammatory Conditions ◽  
Flower Stem ◽  
Ethanolic Extracts ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Acute And Chronic Inflammation ◽  
Inflammatory Effect

Aegle Marmelos Linn (Rutaceae) is used as ethno medicine against various human ailments. Several curde extracts from various parts (Leaves, flower, stem, root etc) of the plant A. marmelos Linn have shown variable anti-inflammatory effects in acute and chronic inflammation in animal models. The anti-inflammatory effects of A marmelos linn may be of special advantage compared to conventional anti-inflammatory drugs. The present study has therefore been undertaken with the objective to evaluate the anti inflammatory effect of aqueous and ethanolic extracts of A. marmelos leaves, compared to a standard anti-inflammatory drug (indomethacin) in chronic inflammatory conditions. The anti-inflammatory effect was studied in rats using cotton pellet implantation, where granuloma formation was used as an index of chronic inflammation. Aqueous and ethanolic extracts of A. marmelos leaves were given orally for 7 days daily at doses of 100 mg/kg body weight. The percent inhibition of granuloma formation following treatment with aqueous and ethanolic extracts of A. marmelos leaves, and indomethacin compared to control were 16.5%, 25.72%, and 39.37% respectively. The differences were statistically significant (p<0.05 in case of aqueous and ethanolic extracts and p<0.001 in case of indomethacin). The results suggest that in case of chronic inflammation, both aqueous and ethanolic extracts of A. marmelos have significant anti- inflammatory effect. The ethanolic extracts compared to aqueous extract produced greater anti- inflammatory effects.Ibrahim Med. Coll. J. 2015; 9(2): 52-54

scholarly journals Nigella Sativa’s Anti-Inflammatory and Antioxidative Effects in Experimental Inflammation

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 921 ◽  
Author(s):  
Raluca Maria Pop ◽  
Octavia Sabin ◽  
Șoimița Suciu ◽  
Stefan Cristian Vesa ◽  
Sonia Ancuța Socaci ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Inflammation ◽  
Antioxidant Activities ◽  
Nigella Sativa ◽  
Control Group ◽  
Acute Administration ◽  
Inflammatory Conditions ◽  
Experimental Inflammation ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Nigella sativa (NS) has been used for centuries in various inflammatory conditions because of its anti-inflammatory and antioxidant activities. The study aimed to evaluate the anti-inflammatory, antinociceptive and antioxidant activity of Nigella sativa oil (NSO) in two models of acute (carrageenan-induced) and sub-acute inflammation (complete Freund’s adjuvant induced) in rats. Materials and Methods: NSO was administered orally 1, 2 and 4 mL/kg in the acute phase. For subacute phase, NSO was administered 4 mL/kg, 7 days before or after inflammation induction, or in association with diclofenac 5 mg/kg. Results: The gas chromatography coupled with mass spectroscopy (GC-MS) analysis showed that NSO is an important source of bioactive compounds, especially p-cymene and thymoquinone. In the acute phase, 1.5 h after administration, NSO (2 and 4 mL/kg) determined an anti-inflammatory effect comparable with that of diclofenac. In the sub-acute administration, NSO had no anti-inflammatory effect. The analgesic effect of NSO was observed only in the sub-acute inflammation in the analgesy-meter test. NSO as treatment proved its antioxidant effect through the reduction of malondialdehyde (MDA) and oxidized glutathione (GSSG), and increases in hydrogen donor capacity (DH) compared to the control group, but the effect was not as intense as that of diclofenac. Conclusion: The present study has proven inconstant anti-inflammatory, analgesic and antioxidative properties of NSO.

Pound the alarm: danger signals in rheumatic diseases

2014 ◽  
Vol 128 (5) ◽  
pp. 297-305 ◽  
Author(s):  
Steven O’Reilly
Keyword(s):  
Nuclear Factor Κb ◽  
Sterile Inflammation ◽  
Nuclear Factor ◽  
Danger Signals ◽  
Rheumatic Conditions ◽  
Molecular Patterns ◽  
Dying Cells ◽  
Damage Associated Molecular Patterns ◽  
Mediate Inflammation

Damage-associated molecular patterns (DAMPs) are chemically heterogeneous endogenous host molecules rapidly released from damaged or dying cells that incite a sterile inflammatory response mediated via pattern recognition receptors (PRRs). The sources of DAMPs are dead or dying cells or the extracellular matrix and can signal through the PRRs, the Toll-like receptors or cytosolic Nod-like receptors, culminating in nuclear factor κB (NF-κB) activation and pro-inflammatory cytokine secretion. Together, these molecules are involved in sterile inflammation and many are associated with rheumatic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythromatosus, psoriatic arthritis and systemic sclerosis. These diseases are associated with inflammation and many danger signals are found in sites of sterile inflammation and mediate inflammation. The present review examines the role of DAMPs in rheumatic conditions and suggests avenues for their therapeutic modulation.

scholarly journals Anti-inflammatory Effect of Semecarpus anacardium LINN. Nut Extract in Acute and Chronic Inflammatory Conditions

2004 ◽  
Vol 27 (12) ◽  
pp. 2028-2031 ◽  
Author(s):  
Vanu Ramkumar Ramprasath ◽  
Palanivelu Shanthi ◽  
Panchanatham Sachdanandam
Keyword(s):  
Semecarpus Anacardium ◽  
Inflammatory Conditions ◽  
Anti Inflammatory ◽  
Inflammatory Effect

scholarly journals Anti inflammatory effect of rhizome of Curcuma longa. Linn, in Albino rats by the method of Carrageenin induced paw oedema

2018 ◽  
Vol 7 (2) ◽  
pp. 229 ◽  
Author(s):  
Jayan Pariyani Savaringal ◽  
Lally M. S.
Keyword(s):  
Curcuma Longa ◽  
Ethanolic Extract ◽  
Inflammatory Activity ◽  
Albino Rats ◽  
Standard Drug ◽  
Medical College ◽  
Inflammatory Conditions ◽  
Anti Inflammatory ◽  
Animal House ◽  
Inflammatory Effect

Background: Curcuma longa or turmeric is a popular Ayurvedic herb, traditionally used for various inflammatory conditions including rheumatoid arthritis and spondylitis. Turmeric which containing phytochemical ingredient curcumin is used in India for centuries as a topical anti inflammatory agent. Many of the currently used anti inflammatory agents like NSAID’s and glucocorticoids have many undesirable adverse effects, especially when they are used for long period. In the present study, Curcuma longa, a plant belonging to the Zingiberaceae family was chosen for investigating its anti-inflammatory effects.Methods: The rhizomes of Curcuma longa were collected locally. The extract was prepared by soxlet extraction with 50% ethanol. Albino rats of Wistar strain (170-250grams) obtained from the animal house of medical college Thiruvananthapuram were used. Aspirin was purchased from sigma Labs, Mumbai. Anti-inflammatory effect of the extract was done in rats by the method of Carrageenin induced paw oedema.Results: The ethanolic extract of Curcuma longa inhibited the development of oedema at the end of 3 hours. The anti-inflammatory activity exhibited by the extract was dose dependent and statistically significant at dose levels of 1000-mg/kg and comparable to that of standard drug used Aspirin.Conclusions: The present study with extract of Curcuma longa revealed that it has significant anti-inflammatory activity.

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