scholarly journals Melatonin Reduces Neuroinflammation and Improves Axonal Hypomyelination by Modulating M1/M2 Microglia Polarization via JAK2-STAT3-Telomerase Pathway in Postnatal Rats Exposed to Lipopolysaccharide

2021 ◽  
Author(s):  
Qiuping Zhou ◽  
Lanfen Lin ◽  
Haiyan Li ◽  
Huifang Wang ◽  
Shuqi Jiang ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Inflammatory Mediators ◽  
Telomerase Reverse Transcriptase ◽  
Melatonin Receptor ◽  
Microglial Polarization ◽  
Proinflammatory Mediators ◽  
M2 Microglia ◽  
M1 Phenotype ◽  
Anti Inflammatory ◽  
Postnatal Rats

AbstractMicroglia activation and associated inflammation are implicated in the periventricular white matter damage (PWMD) in septic postnatal rats. This study investigated whether melatonin would mitigate inflammation and alleviate the axonal hypomyelination in the corpus callosum in septic postnatal rats. We further explored if this might be related to the modulation of microglial polarization from M1 phenotype to M2 through the JAK2/STAT3/telomerase pathway. We reported here that indeed melatonin not only can it reduce the neurobehavioral disturbances in LPS-injected rats, but it can also dampen microglia-mediated inflammation. Thus, in LPS + melatonin group, the expression of proinflammatory mediators in M1 phenotype microglia was downregulated. As opposed to this, M2 microglia were increased which was accompanied by upregulated expression of anti-inflammatory mediators along with telomerase reverse transcriptase or melatonin receptor 1(MT1). In parallel to this was decreased NG2 expression but increased expression of myelin and neurofilament proteins. Melatonin can improve hypomyelination which was confirmed by electron microscopy. In vitro in primary microglia stimulated by LPS, melatonin decreased the expression of proinflammatory mediators significantly; but it increased the expression of anti-inflammatory mediators. Additionally, the expression levels of p-JAK2 and p-STAT3 were significantly elevated in microglia after melatonin treatment. Remarkably, the effect of melatonin on LPS-treated microglia was blocked by melatonin receptor, JAK2, STAT3 and telomerase reverse transcriptase inhibitors, respectively. Taken together, it is concluded that melatonin can attenuate PWMD through shifting M1 microglia towards M2 via MT1/JAK2/STAT3/telomerase pathway. The results suggest a new therapeutic strategy whereby melatonin may be adopted to convert microglial polarization from M1 to M2 phenotype that would ultimately contribute to the attenuation of PWMD.

scholarly journals Melatonin reduces neuroinflammation and improves axonal hypomyelination by modulating M1/M2 microglia polarization via JAK2-STAT3-telomerase pathway in postnatal rats exposed to lipopolysaccharide

2021 ◽  
Author(s):  
Qiuping Zhou ◽  
Lanfen Lin ◽  
Haiyan Li ◽  
Shuqi Jiang ◽  
Huifang Wang ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Periventricular White Matter ◽  
Microglial Polarization ◽  
Proinflammatory Mediators ◽  
M2 Microglia ◽  
Microglia Polarization ◽  
M1 Phenotype ◽  
Anti Inflammatory ◽  
Postnatal Rats

Abstract Microglia activation and associated inflammation are implicated in the periventricular white matter damage (PWMD) in septic postnatal rats. This study investigated whether melatonin would mitigate inflammation and alleviate the axonal hypomyelination in the corpus callosum in septic postnatal rats. We further explored if this might be through modulating microglial polarization from M1 phenotype to M2 through JAK2/STAT3/telomerase pathway. We reported here that melatonin, indeed, not only can it reduce the neurobehavioral disturbances in LPS injected rats, but it can also dampen microglia mediated inflammation. Thus, in LPS + melatonin group, expression of proinflammatory mediators in M1 phenotype microglia was downregulated. As opposed to this, M2 microglia were increased which was accompanied by upregulated expression of anti-inflammatory mediators along with TERT or MT1. In parallel to this was decreased NG2 expression but increased expression of myelin and neurofilament proteins. That melatonin can improve hypomyelination was confirmed by electron microscopy. In vitro in primary microglia stimulated by LPS, melatonin decreased the expression of proinflammatory mediators significantly; but it increased expression of anti-inflammatory mediators. Additionally, the expression levels of p-JAK2 and p-STAT3 were significantly elevated in microglia after melatonin treatment. Remarkably, the melatonin effects on LPS treated microglia was blocked by melatonin receptor, JAK2, STAT3 and telomerase reverse transcriptase inhibitors, respectively. Taken together, it is concluded that melatonin can attenuate PWMD through shifting M1 microglia towards M2 via MT1/JAK2/STAT3/telomerase pathway. The results suggest a new therapeutic strategy whereby melatonin may be adopted to convert microglial polarization that would ultimately contribute to attenuation of PWMD.

scholarly journals Comparative Expression Analyses of Pro- versus Anti-Inflammatory Mediators within Synovium of Patients with Joint Trauma, Osteoarthritis, and Rheumatoid Arthritis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Mohammed A. Al-Madol ◽  
Mohammed Shaqura ◽  
Thilo John ◽  
Rudolf Likar ◽  
Reham Said Ebied ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Mediators ◽  
Inflammatory Process ◽  
Plasma Cells ◽  
Immune Cell ◽  
Proinflammatory Mediators ◽  
Diagnostic Arthroscopy ◽  
Anti Inflammatory ◽  
Joint Trauma ◽  
Specific Mrna

Synovial injury and healing are complex processes including catabolic effects by proinflammatory cytokines and anabolic processes by anti-inflammatory mediators. Here we examined the expression of pro- versus anti-inflammatory mediators in synovium of patients with diagnostic arthroscopy (control), joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). Synovial samples from these patients were subjected to RT-PCR and double immunofluorescence confocal microscopy of pro- and anti-inflammatory mediators as well as immune cell markers. Interestingly, pro- and anti-inflammatory mediators were expressed predominantly in granulocytes in patients with JT and in macrophages, lymphocytes, and plasma cells in patients with OA and RA. Interestingly, parallel to the severity of inflammation, proinflammatory mediators IL-1β, TNF-α, and 5-LOX specific mRNA as well as immunoreactive (IR) cells were significantly more abundant in patients with RA and JT than in those with OA. However, anti-inflammatory mediators 15-LOX, FPR2, and IL-10 specific mRNA as well as IR cells were significantly more abundant in patients with OA than in those with JT and RA. These findings show that upregulation of proinflammatory mediators contributes to the predominantly catabolic inflammatory process in JT and RA synovium, whereas upregulation of anabolic anti-inflammatory mediators counteracts inflammation resulting in the inferior inflammatory process in OA synovium.

scholarly journals Novel Analgesics with Peripheral Targets

2020 ◽  
Vol 17 (3) ◽  
pp. 784-825
Author(s):  
Cosmin I. Ciotu ◽  
Michael J. M. Fischer
Keyword(s):  
Sensory Neurons ◽  
Inflammatory Mediators ◽  
Inflammatory Process ◽  
Early Stage ◽  
Cellular Level ◽  
Proinflammatory Mediators ◽  
Inflammation Targeting ◽  
Anti Inflammatory ◽  
Current Stage ◽  
Inflammatory Effect

Abstract A limited number of peripheral targets generate pain. Inflammatory mediators can sensitize these. The review addresses targets acting exclusively or predominantly on sensory neurons, mediators involved in inflammation targeting sensory neurons, and mediators involved in a more general inflammatory process, of which an analgesic effect secondary to an anti-inflammatory effect can be expected. Different approaches to address these systems are discussed, including scavenging proinflammatory mediators, applying anti-inflammatory mediators, and inhibiting proinflammatory or facilitating anti-inflammatory receptors. New approaches are contrasted to established ones; the current stage of progress is mentioned, in particular considering whether there is data from a molecular and cellular level, from animals, or from human trials, including an early stage after a market release. An overview of publication activity is presented, considering a IuPhar/BPS-curated list of targets with restriction to pain-related publications, which was also used to identify topics.

scholarly journals Pomiferin Exerts Anti-Neuroinflammatory Effects Through Activating Akt /Nrf2 Pathway and Inhibiting NF-κB pathway

2021 ◽  
Author(s):  
Yan Zhao ◽  
Yuxuan Sang ◽  
Yanan Sun ◽  
Jie Wu
Keyword(s):  
Neurodegenerative Diseases ◽  
Quantitative Pcr ◽  
Inflammatory Mediators ◽  
Peripheral Tissues ◽  
Nrf2 Pathway ◽  
Proinflammatory Mediators ◽  
Bv2 Cells ◽  
Tnf Α ◽  
Wide Range ◽  
Anti Inflammatory

Abstract Background:Neurodegenerative diseases are associated with neuroinflammation. However, the pro-inflammatory mediators produced during the occurrence of neuroinflammation will damage neurons and aggravate the process of neurodegenerative diseases. Therefore, inhibiting neuroinflammation may be an effective way to alleviate neurodegenerative diseases. The orange mulberry brass has a wide range of anti - oxidation and anti - inflammatory effects in peripheral tissues. However, it is not clear whether it inhibits neuroinflammation. Methods:In our experiment, we studied the effect of Pomiferin on BV2 cell inflammation and its mechanism with Quantitative PCR, ELISA and western blot.Results:The results showed that Pomiferin inhibited the production of ROS, NO and proinflammatory mediators (IL-6, TNF-α, iNOS, COX2) in BV2 cells. Further mechanism studies showed that Pomiferin activated the Akt /Nrf2 pathway and inhibited the NF-κB pathway. Conclusion: Our study demonstrated that Pomiferin exerts anti-neuroinflammatory effects through activating Akt /Nrf2 pathway and inhibiting NF-κB pathway.

scholarly journals Dietary Short-Term Fiber Interventions in Arthritis Patients Increase Systemic SCFA Levels and Regulate Inflammation

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3207
Author(s):  
Kerstin Dürholz ◽  
Jörg Hofmann ◽  
Aida Iljazovic ◽  
Julian Häger ◽  
Sébastien Lucas ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Dietary Intervention ◽  
Inflammatory Diseases ◽  
Joint Damage ◽  
Short Chain Fatty Acids ◽  
Routine Care ◽  
Short Term ◽  
High Fiber ◽  
Proinflammatory Mediators ◽  
Anti Inflammatory

Chronic inflammatory diseases are often initiated and guided by the release of proinflammatory mediators. Rheumatoid arthritis (RA) is caused by an imbalance between the pro- and anti-inflammatory mediators in the joints, thereby favoring chronic inflammation and joint damage. Here, we investigate if short-term high-fiber dietary intervention shifts this towards anti-inflammatory mediators. Healthy controls (n = 10) and RA patients (n = 29) under routine care received daily high-fiber bars for 15 or 30 days, respectively. Stool and sera were analyzed for pro- and anti-inflammatory mediators. A high-fiber dietary intervention resulted in increased anti-inflammatory short-chain fatty acids (SCFA), decreased proarthritic cytokine concentrations, along with a durable shift in the Firmicutes-to-Bacteroidetes ratio. Together, these results further strengthen high-fiber dietary interventions as a practical approach complementing existing pharmacological therapies.

scholarly journals Anti-Inflammatory Effect of Recreational Exercise in TNBS-Induced Colitis in Rats: Role of NOS/HO/MPO System

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Zita Szalai ◽  
András Szász ◽  
István Nagy ◽  
László G. Puskás ◽  
Krisztina Kupai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physical Exercise ◽  
Inflammatory Mediators ◽  
Wheel Running ◽  
Treated Group ◽  
Mucosal Damage ◽  
Proinflammatory Mediators ◽  
Male Wistar Rats ◽  
Anti Inflammatory ◽  
Oxide Synthase

There are opposite views in the available literature: Whether physical exercise has a protective effect or not on the onset of inflammatory bowel disease (IBD). Therefore, we investigated the effects of recreational physical exercise before the induction of colitis. After 6 weeks of voluntary physical activity (running wheel), male Wistar rats were treated with TNBS (10 mg). 72 hrs after trinitrobenzene sulphonic acid (TNBS) challenge we measured colonic gene (TNF-α, IL-1β, CXCL1 and IL-10) and protein (TNF-α) expressions of various inflammatory mediators and enzyme activities of heme oxygenase (HO), nitric oxide synthase (NOS), and myeloperoxidase (MPO) enzymes. Wheel running significantly increased the activities of HO, constitutive NOS (cNOS) isoform. Furthermore, 6 weeks of running significantly decreased TNBS-induced inflammatory markers, including extent of lesions, severity of mucosal damage, and gene expression of IL-1β, CXCL1, and MPO activity, while IL-10 gene expression and cNOS activity were increased. iNOS activity decreased and the activity of HO enzyme increased, but not significantly, compared to the sedentary TNBS-treated group. In conclusion, recreational physical exercise can play an anti-inflammatory role by downregulating the gene expression of proinflammatory mediators, inducing anti-inflammatory mediators, and modulating the activities of HO and NOS enzymes in a rat model of colitis.

scholarly journals In vitro evaluation of selligueain A effects on the proinflammatory mediators production in RAW264.7 murine macrophages

2021 ◽  
Vol 10 (3) ◽  
pp. 313-318
Author(s):  
Deden Winda Suwandi ◽  
Tina Rostnawati ◽  
Muchtaridi Muchtaridi ◽  
Anas Subarnas
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Mediators ◽  
Cell Model ◽  
Inflammatory Activity ◽  
Raw264.7 Cells ◽  
Proinflammatory Mediators ◽  
Tnf Α ◽  
Anti Inflammatory

Introduction: Selligueain A derived from the roots of Polypodium feei was shown to have anti-inflammatory activity, which was tested in vivo on the rats’ paw edema induced by carrageenan. The aim of this study was to evaluate the anti-inflammatory mechanism of selligueain A in vitro against the production of pro-inflammatory mediators. Methods: In this study, RAW264.7 cells were used as an inflammatory cell model, and observations were made on the inflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), and tumour necrosis factor-α (TNF-α). The NO concentration was measured by the Griess reaction, and the iNOS enzyme and the TNF-α concentrations were determined by the ELISA method. Cell viability was assessed by the [3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] (MTS) test. Results: Selligueain A at concentrations of 100 and 150 µM suppressed the production of NO, iNOS, and TNF-α in RAW264.7 cells stimulated by lipopolysaccharide (LPS). The concentration of 150 µM showed the highest inhibition of NO, iNOS, and TNF-α mediators with the percentage inhibition of 64.85, 55.01, and 48.54%, respectively. Conclusion: This study shows that selligueain A has anti-inflammatory activity through inhibition of NO, iNOS, and TNF-α production in RAW264.7 macrophage cells.

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