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 POS1223 RAS GUANYL RELEASING PROTEIN 1 (RASGRP1) IN PERIPHERAL B CELLS LINKS RA TO COVID-19

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 895.2-895
Author(s):  
S. Hannawi ◽  
F. Alqutami ◽  
M. Y. Hachim
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Plasma Cells ◽  
Immune Cell ◽  
In Silico Analysis ◽  
Differentially Expressed ◽  
Transcriptional Enhancer ◽  
Activated T Cells

Background:Changes in the B cell subpopulations is a hallmark of the antiviral response against SARS-CoV-2 and is associated with COVID-19 severity (1). Recently our group showed common derangement observed in rheumatoid arthritis (RA) and COVID-19 (2). In RA, synovium attracts potentially autoreactive—B cells and plasma cells that play a central role in RA pathogenesis (3). We were interested to know the similarity in B cell’s transcriptomic changes specific to RA and COVID-19.Objectives:Identify similar upregulated genes in synovium and B cells in RA and at the same time are differentially expressed in B cells infected with SARS-CoV-2 or from COVID-19 patients.Methods:RNAseq dataset (GSE89408) of (218) samples isolated from joint synovial biopsies from subjects with and without rheumatoid arthritis were retrieved from GEO online database. Differentially expressed genes (DRGs) specific to RA were identified after exclusion of those upregulated in Osteoarthritis or other joint condition samples in the same dataset. The RA specific genes were intersected with DEGs between B cells from healthy versus RA as extracted from (GSE110999) dataset. The shortlisted genes specifically upregulated in B cells of RA were identified and were explored in B cells COVID-19 transcriptome datasets using (https://metascape.org/COVID).Results:60 genes were found to be specifically upregulated in RA synovium and B cells and are changed in B cells infected with SARS-CoV-2 or from COVID-19 patients, Figure (1-A). Those genes were involved in interferon signaling, antiviral and immune cell activation. RASGRP1 was common between B cells of RA and COVID-19 and might play a role in the pathogenesis of both, Figure (1-B). RASGRP1 controls ERK/MAPK kinase cascade needed in B-/T-cell differentiation and development. It is vital to protect against viral infection and the autoimmune associated proliferation of activated T-cells like RA (4). We checked its level in another dataset (GSE152641) of the whole blood RNASeq of 62 COVID-19 patients and 24 healthy controls. RASGRP1 was significantly down in COVID-19 compared to healthy control, Figure (1-C).Conclusion:SARS-CoV-2 impair B and T’s cells’ immune response through its action on RASGRP1 and that can be a novel mechanistic explanation of how the virus decreases immune cells and impair the B cell’s humoral immunity.References:[1]Sosa-Hernández VA, Torres-Ruíz J, Cervantes-Díaz R, Romero-Ramírez S, Páez-Franco JC, Meza-Sánchez DE, et al. B Cell Subsets as Severity-Associated Signatures in COVID-19 Patients. Frontiers in Immunology. 2020;11(3244).[2]Hachim MY, Hachim IY, Naeem KB, Hannawi H, Al Salmi I, Hannawi S. C-C chemokine receptor type 5 links COVID-19, rheumatoid arthritis, and Hydroxychloroquine: in silico analysis. Translational Medicine Communications. 2020;5(1):14.[3]Doorenspleet ME, Klarenbeek PL, de Hair MJ, van Schaik BD, Esveldt RE, van Kampen AH, et al. Rheumatoid arthritis synovial tissue harbours dominant B-cell and plasma-cell clones associated with autoreactivity. Ann Rheum Dis. 2014;73(4):756-62.[4]Molineros JE, Singh B, Terao C, Okada Y, Kaplan J, McDaniel B, et al. Mechanistic Characterization of RASGRP1 Variants Identifies an hnRNP-K-Regulated Transcriptional Enhancer Contributing to SLE Susceptibility. Frontiers in Immunology. 2019;10(1066).Disclosure of Interests:None declared

scholarly journals Prostanoid Receptor Subtypes and Its Endogenous Ligands with Processing Enzymes within Various Types of Inflammatory Joint Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Mohammed A. Al-Madol ◽  
Mohammed Shaqura ◽  
Thilo John ◽  
Rudolf Likar ◽  
Reham Said Ebied ◽  
...  
Keyword(s):  
Synovial Tissue ◽  
Expression Profile ◽  
Inflammatory Process ◽  
Plasma Cells ◽  
Immune Cell ◽  
Receptor Subtypes ◽  
Prostanoid Receptor ◽  
Processing Enzymes ◽  
Target Molecules ◽  
Cox 2

A complex inflammatory process mediated by proinflammatory cytokines and prostaglandins commonly occurs in the synovial tissue of patients with joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). This study systematically investigated the distinct expression profile of prostaglandin E2 (PGE2), its processing enzymes (COX-2), and microsomal PGES-1 (mPGES-1) as well as the corresponding prostanoid receptor subtypes (EP1-4) in representative samples of synovial tissue from these patients (JT, OA, and RA). Quantitative TaqMan®-PCR and double immunofluorescence confocal microscopy of synovial tissue determined the abundance and exact immune cell types expressing these target molecules. Our results demonstrated that PGE2 and its processing enzymes COX-2 and mPGES-1 were highest in the synovial tissue of RA, followed by the synovial tissue of OA and JT patients. Corresponding prostanoid receptor, subtypes EP3 were highly expressed in the synovium of RA, followed by the synovial tissue of OA and JT patients. These proinflammatory target molecules were distinctly identified in JT patients mostly in synovial granulocytes, in OA patients predominantly in synovial macrophages and fibroblasts, whereas in RA patients mainly in synovial fibroblasts and plasma cells. Our findings show a distinct expression profile of EP receptor subtypes and PGE2 as well as the corresponding processing enzymes in human synovium that modulate the inflammatory process in JT, OA, and RA patients.

Proinflammatory and Anti-inflammatory Genes in Stroke Pathogenesis

2020 ◽  
Vol 26 (34) ◽  
pp. 4220-4233
Author(s):  
Mengmeng Jiang ◽  
Penglin Yin ◽  
Xiaodan Bai ◽  
Liji Yang ◽  
Junping Zhang ◽  
...  
Keyword(s):  
Inflammatory Process ◽  
Ischemic Brain ◽  
Inflammatory Genes ◽  
Proinflammatory Mediators ◽  
Inflammatory Mechanism ◽  
Ischemic Brain Tissue ◽  
Anti Inflammatory ◽  
The Brain

The brain's response to ischemic injury is an acute and long-term inflammatory process. This process involves activation of resident cells (mainly microglia, hematogenous macrophages), production of proinflammatory mediators and infiltration of various proinflammatory cells (mainly neutrophils and lymphocytes). These cells play an essential role in ischemic brain tissue by releasing either proinflammatory or anti-inflammatory mediators at different time points. However, the exact pathogenesis of proinflammatory or anti-inflammatory genes in this process has not yet been elucidated. This review aims to investigate the inflammatory process of stroke, especially the role of proinflammatory and anti-inflammatory genes in the pathogenesis of stroke. We also summarize the current clinical trials of drugs that target the inflammatory mechanism for intervention.

scholarly journals The Immunomodulatory and Anti-Inflammatory Effect of Curcumin on Immune Cell Populations, Cytokines, and In Vivo Models of Rheumatoid Arthritis

2021 ◽  
Vol 14 (4) ◽  
pp. 309
Author(s):  
Sebastian Makuch ◽  
Kamil Więcek ◽  
Marta Woźniak
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Cells ◽  
Immune Cell ◽  
Autoimmune Disorder ◽  
Lymphoid Cells ◽  
In Vivo Models ◽  
Rheumatoid Arthritis Development ◽  
Bone Degradation ◽  
Anti Inflammatory

Rheumatoid arthritis (RA) is a widespread chronic autoimmune disorder affecting the joints, causing irreversible cartilage, synovium, and bone degradation. During the course of the disease, many immune and joint cells are activated, causing inflammation. Immune cells including macrophages, lymphocytes, neutrophils, mast cells, natural killer cells, innate lymphoid cells, as well as synovial tissue cells, like fibroblast-like synoviocytes, chondrocytes, and osteoclasts secrete different proinflammatory factors, including many cytokines, angiogenesis-stimulating molecules and others. Recent studies reveal that curcumin, a natural dietary anti-inflammatory compound, can modulate the response of the cells engaging in RA course. This review comprises detailed data about the pathogenesis and inflammation process in rheumatoid arthritis and demonstrates scientific investigations about the molecular interactions between curcumin and immune cells responsible for rheumatoid arthritis development to discuss this herbal drug’s immunoregulatory role in RA treatment.

scholarly journals Systemic anti-inflammatory mediators in COPD: increase in soluble interleukin 1 receptor II during treatment of exacerbations

Thorax ◽  
2001 ◽  
Vol 56 (9) ◽  
pp. 721-726
Author(s):  
M A Dentener ◽  
E C Creutzberg ◽  
A M W J Schols ◽  
A Mantovani ◽  
C van‘t Veer ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Inflammatory Process ◽  
Interleukin 1 ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Tumour Necrosis Factor Receptor ◽  
Obstructive Pulmonary Disease ◽  
Reactive Protein ◽  
Inflammatory Mechanism ◽  
Anti Inflammatory

BACKGROUNDThe aim of this study was to test the hypothesis that the chronic inflammatory process present in chronic obstructive pulmonary disease (COPD) is due to a defective endogenous anti-inflammatory mechanism.METHODSSystemic levels of the anti-inflammatory mediators soluble interleukin 1 receptor II (sIL-1RII), soluble tumour necrosis factor receptor p55 (sTNF-R55) and sTNF-R75, and of C reactive protein (CRP) and lipopolysaccharide binding protein (LBP) were analysed in 55 patients with stable COPD (median forced expiratory volume in one second (FEV1) 34% predicted (range 15–78)) and compared with levels in 23 control subjects. In addition, changes in these mediators were studied in 13 patients with COPD (median FEV1 34% predicted (range 19–51)) during the first 7 days in hospital with an exacerbation of the disease.RESULTSPatients with stable COPD were characterised by a systemic inflammatory process indicated by an increased leucocyte count (7.2 (4.7–16.4)v 4.8 (3.5–8.3) × 109/l), raised levels of CRP (11.8 (1.1–75.0) v 4.1 (0.6–75.0) μg/ml) and LBP (45.6 (8.1–200.0)v 27.9 (14.1–71.5) μg/ml), and moderate increases in both sTNF-Rs. In contrast, the sIL-1RII level did not differ between patients and controls (4.53 (2.09–7.60)v 4.63 (3.80–5.93) ng/ml). During treatment of disease exacerbations, systemic levels of both CRP (at day 3) and LBP (at day 7) were significantly reduced compared with day 1, whereas sIL-1RII levels increased.CONCLUSIONSThese data suggest an imbalance in systemic levels of pro- and anti-inflammatory mediators in patients with stable COPD. The increase in the anti-inflammatory mediator sIL-1RII during treatment of exacerbations may contribute to the clinical improvement.

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 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.

Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells

Blood ◽  
2011 ◽  
Vol 117 (16) ◽  
pp. 4273-4283 ◽  
Author(s):  
Thomas Weichhart ◽  
Michael Haidinger ◽  
Karl Katholnig ◽  
Chantal Kopecky ◽  
Marko Poglitsch ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Clinical Importance ◽  
Innate Immune ◽  
Negative Regulator ◽  
Innate Immune Cells ◽  
Myeloid Dendritic Cells ◽  
Mtor Inhibition ◽  
Proinflammatory Mediators ◽  
Anti Inflammatory

Abstract A central role for the mammalian target of rapamycin (mTOR) in innate immunity has been recently defined by its ability to limit proinflammatory mediators. Although glucocorticoids (GCs) exert potent anti-inflammatory effects in innate immune cells, it is currently unknown whether the mTOR pathway interferes with GC signaling. Here we show that inhibition of mTOR with rapamycin or Torin1 prevented the anti-inflammatory potency of GC both in human monocytes and myeloid dendritic cells. GCs could not suppress nuclear factor-κB and JNK activation, the expression of proinflammatory cytokines, and the promotion of Th1 responses when mTOR was inhibited. Interestingly, long-term activation of monocytes with lipopolysaccharide enhanced the expression of TSC2, the principle negative regulator of mTOR, whereas dexamethasone blocked TSC2 expression and reestablished mTOR activation. Renal transplant patients receiving rapamycin but not those receiving calcineurin inhibitors displayed a state of innate immune cell hyper-responsiveness despite the concurrent use of GC. Finally, mTOR inhibition was able to override the healing phenotype of dexamethasone in a murine lipopolysaccharide shock model. Collectively, these data identify a novel link between the glucocorticoid receptor and mTOR in innate immune cells, which is of considerable clinical importance in a variety of disorders, including allogeneic transplantation, autoimmune diseases, and cancer.

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.

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