scholarly journals Selected Uterine Immune Events Associated With the Establishment of Pregnancy in the Dog

2021 ◽  
Vol 7 ◽  
Author(s):  
Miguel Tavares Pereira ◽  
Renata Nowaczyk ◽  
Rita Payan-Carreira ◽  
Sonia Miranda ◽  
Selim Aslan ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Trophoblast Invasion ◽  
Tnf Receptors ◽  
Related Factors ◽  
Inflammatory Conditions ◽  
Inflammatory Signals ◽  
Anti Inflammatory ◽  
Uterine Glands ◽  
Post Implantation ◽  
Implantation Period

In the dog, implantation takes place at approximately 17 days of embryonal life and, while exposed to relatively high circulating progesterone concentrations, embryos presence is required for the formation of decidua. Furthermore, a balance between pro- and anti-inflammatory responses in conceptus-maternal communication is crucial for the onset of pregnancy. Strikingly, the understanding of such immune mechanisms in canine reproduction is still elusive. Here, canine uterine samples from pre-implantation (day 10–12, E+) and corresponding non-pregnant controls (E–), implantation (day 17, Imp) and post-implantation (day 18–25, Post-Imp) stages of pregnancy were used to investigate the expression and localization of several immune-related factors. The most important findings indicate increased availability of CD4, MHCII, NCR1, IDO1, AIF1, CD25, CCR7, and IL6 in response to embryo presence (E+), while FoxP3 and CCL3 were more abundant in E– samples. Implantation was characterized by upregulated levels of FoxP3, IL12a, ENG, and CDH1, whereas CD4, CCR7, IL8, and -10 were less represented. Following implantation, decreased transcript levels of TNFR1, MHCII, NCR1, TLR4, CD206, FoxP3, and IL12a were observed concomitantly with the highest expression of IL6 and IL1β. MHCII, CD86, CD206, CD163, TNFα, IDO1, and AIF1 were immunolocalized in macrophages, CD4 and Nkp46 in lymphocytes, and some signals of IDO1, AIF1, and TNF-receptors could also be identified in endothelial cells and/or uterine glands. Cumulatively, new insights regarding uterine immunity in the peri-implantation period are provided, with apparent moderated pro-inflammatory signals prevailing during pre-implantation, while implantation and early trophoblast invasion appear to be associated with immunomodulatory and rather anti-inflammatory conditions.

scholarly journals Trem2promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions

2018 ◽  
Author(s):  
Wenfei Liu ◽  
Orjona Taso ◽  
Rui Wang ◽  
Sevinc Bayram ◽  
Pablo Garcia-Reitboeck ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Inflammatory Responses ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Similar Expression Profile ◽  
Inflammatory Conditions ◽  
Phenotype Comparison ◽  
Inflammatory Phenotype ◽  
Similar Phenotype ◽  
Anti Inflammatory

AbstractGenome-wide association studies have reported that, amongst other microglial genes, variants inTREM2can profoundly increase the incidence of developing Alzheimer’s disease (AD). We have investigated the role of TREM2 in primary microglial cultures from wild type mice by using siRNA to decreaseTrem2expression, and in parallel from knock-in mice heterozygous or homozygous for theTrem2R47H AD risk variant. The prevailing phenotype ofTrem2R47H knock-in mice was decreased expression levels ofTrem2in microglia, which resulted in decreased density of microglia in the hippocampus. Overall, primary microglia with reducedTrem2expression, either by siRNA or from the R47H knock-in mice, displayed a similar phenotype. Comparison of the effects of decreasedTrem2expression under conditions of LPS pro-inflammatory or IL-4 anti-inflammatory stimulation revealed the importance ofTrem2in driving a number of the genes up-regulated in the anti-inflammatory phenotype. RNA-seq analysis showed that IL-4 induced the expression of a programme of genes includingArg1andAp1b1in microglia, which showed an attenuated response to IL-4 whenTrem2expression was decreased. Genes showing a similar expression profile toArg1were enriched for STAT6 transcription factor recognition elements in their promoter, andTrem2knockdown decreased levels of the transcription factor STAT6. LPS-induced pro-inflammatory stimulation suppressedTrem2expression, thus preventing TREM2’s anti-inflammatory drive. Given that anti-inflammatory signaling is associated with tissue repair, understanding the signaling mechanisms downstream ofTrem2in coordinating the pro- and anti-inflammatory balance of microglia, particularly mediating effects of the IL-4-regulated anti-inflammatory pathway, has important implications for fighting neurodegenerative disease.Graphical abstract

scholarly journals Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions

2020 ◽  
Vol 29 (19) ◽  
pp. 3224-3248
Author(s):  
Wenfei Liu ◽  
Orjona Taso ◽  
Rui Wang ◽  
Sevinc Bayram ◽  
Andrew C Graham ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Similar Expression Profile ◽  
Inflammatory Conditions ◽  
Genome Wide ◽  
Phenotype Comparison ◽  
Inflammatory Phenotype ◽  
Similar Phenotype ◽  
Anti Inflammatory

Abstract Genome-wide association studies have reported that, amongst other microglial genes, variants in TREM2 can profoundly increase the incidence of developing Alzheimer’s disease (AD). We have investigated the role of TREM2 in primary microglial cultures from wild type mice by using siRNA to decrease Trem2 expression, and in parallel from knock-in mice heterozygous or homozygous for the Trem2 R47H AD risk variant. The prevailing phenotype of Trem2 R47H knock-in mice was decreased expression levels of Trem2 in microglia, which resulted in decreased density of microglia in the hippocampus. Overall, primary microglia with reduced Trem2 expression, either by siRNA or from the R47H knock-in mice, displayed a similar phenotype. Comparison of the effects of decreased Trem2 expression under conditions of lipopolysaccharide (LPS) pro-inflammatory or IL-4 anti-inflammatory stimulation revealed the importance of Trem2 in driving a number of the genes up-regulated in the anti-inflammatory phenotype. RNA-seq analysis showed that IL-4 induced the expression of a program of genes including Arg1 and Ap1b1 in microglia, which showed an attenuated response to IL-4 when Trem2 expression was decreased. Genes showing a similar expression profile to Arg1 were enriched for STAT6 transcription factor recognition elements in their promoter, and Trem2 knockdown decreased levels of STAT6. LPS-induced pro-inflammatory stimulation suppressed Trem2 expression, thus preventing TREM2’s anti-inflammatory drive. Given that anti-inflammatory signaling is associated with tissue repair, understanding the signaling mechanisms downstream of Trem2 in coordinating the pro- and anti-inflammatory balance of microglia, particularly mediating effects of the IL-4-regulated anti-inflammatory pathway, has important implications for fighting neurodegenerative disease.

scholarly journals The Role of Maresins in Inflammatory Pain: Function of Macrophages in Wound Regeneration

2019 ◽  
Vol 20 (23) ◽  
pp. 5849 ◽  
Author(s):  
Sung-Min Hwang ◽  
Gehoon Chung ◽  
Yong Ho Kim ◽  
Chul-Kyu Park
Keyword(s):  
Inflammatory Pain ◽  
Inflammatory Responses ◽  
M2 Macrophage ◽  
Macrophage Phenotype ◽  
New Class ◽  
Inflammatory Conditions ◽  
Signaling Mechanisms ◽  
Macrophage Phagocytosis ◽  
Anti Inflammatory

Although acute inflammatory responses are host-protective and generally self-limited, unresolved and delayed resolution of acute inflammation can lead to further tissue damage and chronic inflammation. The mechanism of pain induction under inflammatory conditions has been studied extensively; however, the mechanism of pain resolution is not fully understood. The resolution of inflammation is a biosynthetically active process, involving specialized pro-resolving mediators (SPMs). In particular, maresins (MaRs) are synthesized from docosahexaenoic acid (DHA) by macrophages and have anti-inflammatory and pro-resolving capacities as well as tissue regenerating and pain-relieving properties. A new class of macrophage-derived molecules—MaR conjugates in tissue regeneration (MCTRs)—has been reported to regulate phagocytosis and the repair and regeneration of damaged tissue. Macrophages not only participate in the biosynthesis of SPMs, but also play an important role in phagocytosis. They exhibit different phenotypes categorized as proinflammatory M1-like phenotypes and anti-inflammatory M2 phenotypes that mediate both harmful and protective functions, respectively. However, the signaling mechanisms underlying macrophage functions and phenotypic changes have not yet been fully established. Recent studies report that MaRs help resolve inflammatory pain by enhancing macrophage phagocytosis and shifting cytokine release to the anti-inflammatory M2 phenotypes. Consequently, this review elucidated the characteristics of MaRs and macrophages, focusing on the potent action of MaRs to enhance the M2 macrophage phenotype profiles that possess the ability to alleviate inflammatory pain.

scholarly journals The Cholinergic Anti-Inflammatory Pathway as a Conceptual Framework to Treat Inflammation-Mediated Renal Injury

2019 ◽  
Vol 44 (4) ◽  
pp. 435-448 ◽  
Author(s):  
Jonas Jarczyk ◽  
Benito A. Yard ◽  
Simone Hoeger
Keyword(s):  
Vagus Nerve ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Kidney Injury ◽  
Organ Injury ◽  
Inflammatory Pathway ◽  
Inflammatory Conditions ◽  
Promising Strategy ◽  
Anti Inflammatory ◽  
The Brain

Background: The cholinergic anti-inflammatory pathway, positioned at the interface of the nervous and immune systems, is the efferent limb of the “inflammatory reflex” which mainly signals through the vagus nerve. As such, the brain can modulate peripheral inflammatory responses by the activation of vagal efferent fibers. Importantly, immune cells in the spleen express most cholinergic system components such as acetylcholine (ACh), choline acetyltransferase, acetylcholinesterase, and both muscarinic and nicotinic ACh receptors, making communication between both systems possible. In general, this communication down-regulates the inflammation, achieved through different mechanisms and depending on the cells involved. Summary: With the awareness that the cholinergic anti-inflammatory pathway serves to prevent or limit inflammation in peripheral organs, vagus nerve stimulation has become a promising strategy in the treatment of several inflammatory conditions. Both pharmacological and non-pharmacological methods have been used in many studies to limit organ injury as a consequence of inflammation. Key Messages: In this review, we will highlight our current knowledge of the cholinergic anti-inflammatory pathway, with emphasis on its potential clinical use in the treatment of inflammation-triggered kidney injury.

scholarly journals Necrotizing Fasciitis: Low-Dose Radiotherapy as a Potential Adjunct Treatment

Dose-Response ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 155932581987175 ◽  
Author(s):  
Gaurav Dhawan ◽  
Rachna Kapoor ◽  
Asha Dhamija ◽  
Ravinder Singh ◽  
Bharat Monga ◽  
...  
Keyword(s):  
Necrotizing Fasciitis ◽  
Low Dose ◽  
Inflammatory Responses ◽  
Low Cost ◽  
Adjunct Treatment ◽  
Inflammatory Conditions ◽  
Low Dose Radiotherapy ◽  
Cost Of Health Care ◽  
Anti Inflammatory ◽  
Effective Use

Necrotizing fasciitis (NF) is a rapidly spreading bacterial infection causing extensive tissue necrosis and destruction. Despite appropriate therapy, the disease results in significant morbidity/mortality and substantial treatment costs. Several studies published in the early 1900s demonstrated the effective use of low-dose X-ray radiotherapy (RT) for the treatment of many diverse inflammatory conditions and diseases (eg, gas gangrene, sinus infections, arthritis, tendonitis, and serious inflammatory lung conditions). The mechanism by which therapeutic RT doses produce positive patient outcomes is related at least in part to its capacity to induce tissue-based anti-inflammatory responses. This action is due to the polarization of macrophages to an anti-inflammatory or M2 phenotype via optimized low-dose RT. Low-dose RT has the potential to significantly reduce debilitating surgeries and aggressive treatments required for NF, providing a 3-prong benefit in terms of patient mortality, length of hospitalization stays, and cost of health care (both short term and long term). Low cost and easy availability of low-dose RT makes it a potentially useful option for patients of every age-group. In addition, low-dose RT may be a particularly useful option in countries treating many patients who are unable to afford surgeries, antibiotics, and hyperbaric oxygen.

scholarly journals Metabolic Reprogramming in Mitochondria of Myeloid Cells

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 5 ◽  
Author(s):  
Hao Zuo ◽  
Yihong Wan
Keyword(s):  
Fatty Acid ◽  
Oxidative Phosphorylation ◽  
Inflammatory Responses ◽  
Myeloid Cells ◽  
Metabolic Reprogramming ◽  
Glutamine Metabolism ◽  
Mitochondrial Morphology ◽  
Inflammatory Signals ◽  
Anti Inflammatory ◽  
Inflammatory Effect

The myeloid lineage consists of multiple immune cell types, such as macrophages, monocytes, and dendritic cells. It actively participates in both innate and adaptive immunity. In response to pro- or anti-inflammatory signals, these cells undergo distinct programmed metabolic changes especially in mitochondria. Pro-inflammatory signals induce not only a simple shift from oxidative phosphorylation to glycolysis, but also complicated metabolic alterations during the early and tolerant stages in myeloid cells. In mitochondria, a broken Krebs cycle leads to the accumulation of two metabolites, citrate and succinate, both of which trigger pro-inflammatory responses of myeloid cells. A deficient electron transport chain induces pro-inflammatory responses in the resting myeloid cells while it suppresses these responses in the polarized cells during inflammation. The metabolic reprogramming in mitochondria is also associated with altered mitochondrial morphology. On the other hand, intact oxidative phosphorylation is required for the anti-inflammatory functions of myeloid cells. Fatty acid synthesis is essential for the pro-inflammatory effect and glutamine metabolism in mitochondria exhibits the anti-inflammatory effect. A few aspects of metabolic reprogramming remain uncertain, for example, glycolysis and fatty acid oxidation in anti-inflammation. Overall, metabolic reprogramming is an important element of immune responses in myeloid cells.

scholarly journals The levels of circulating cytokines in the early post-implantation period

2017 ◽  
Vol 98 (6) ◽  
pp. 938-943 ◽  
Author(s):  
N A Panakhov ◽  
T G Makhmudo
Keyword(s):  
Blood Serum ◽  
Inflammatory Cytokines ◽  
Soft Tissues ◽  
Dental Implantation ◽  
Cytokine Levels ◽  
Before And After ◽  
Anti Inflammatory ◽  
Gingival Fluid ◽  
Post Implantation ◽  
Implantation Period

Aim. Analysis of cytokine levels in the blood and dentogingival fluid in patients before and after dental implantation. Methods. 164 patients with dental implants were examined, the average age was 54.6±4.17 years. Dental implantation was performed in one- and two-step procedures, osteoplastic materials Geistlich Bio-Oss spongiosa granules 0.5 g and Bio-Gide membranes 25×25 mm (Germany) were used. A total of 641 implants were installed. The course of post-implantation period was studied in all patients on days 1-3 and 6-7. Dental fluid was collected from each implant with sterile filter paper strips «F». The level of pro- and anti-inflammatory cytokines were measured in the blood serum and gingival fluid before and 6-7 days after intervention by the solid-phase ELISA method. Results. Immediately after implantation (1-2 days), all patients noted soreness, swelling and hyperemia, which on day 3 regressed in 139 (84.6%) patients, and 25 (15.2%) patients were diagnosed with acute mucositis, manifested by edema and hyperemia of soft tissues in the implant area. After dental implantation, imbalance of pro- and anti-inflammatory cytokines was observed, especially in complicated cases. The most pronounced changes were noted in the concentration of TNFα, IL-1β and IL-6. Predominance of hyperproduction of pro-inflammatory cytokines in acute mucositis was revealed. The ratio of pro- and anti-inflammatory cytokines in acute mucositis was increased by 5.5 times (p <0.001) in the blood and by 5.0 times (p <0.001) in gingival fluid. Conclusion. Time course of cytokine levels in blood serum and gingival fluid before and after dental implantation indicate changes in the balance of pro- and anti-inflammatory cytokines; an increase of the production of anti-inflammatory cytokines is especially pronounced against the background of acute mucositis and changes in the level of anti-inflammatory interleukin-4 and -10 have multidirectional character.

scholarly journals Myeloid-Derived Suppressor Cells Evolve during Sepsis and Can Enhance or Attenuate the Systemic Inflammatory Response

2012 ◽  
Vol 80 (6) ◽  
pp. 2026-2034 ◽  
Author(s):  
Laura Brudecki ◽  
Donald A. Ferguson ◽  
Charles E. McCall ◽  
Mohamed El Gazzar
Keyword(s):  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Cecal Ligation ◽  
Suppressor Cells ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Myeloid Derived Suppressor Cells ◽  
Inflammatory Conditions ◽  
Anti Inflammatory

ABSTRACTMyeloid-derived suppressor cells (MDSCs) are a heterogeneous Gr1+CD11b+population of immature cells containing granulocytic and monocytic progenitors, which expand under nearly all inflammatory conditions and are potent repressors of T-cell responses. Studies of MDSCs during inflammatory responses, including sepsis, suggest they can protect or injure. Here, we investigated MDSCs during early and late sepsis. To do this, we used our published murine model of cecal ligation and puncture (CLP)-induced polymicrobial sepsis, which transitions from an early proinflammatory phase to a late anti-inflammatory and immunosuppressive phase. We confirmed that Gr1+CD11b+MDSCs gradually increase after CLP, reaching ∼88% of the bone marrow myeloid series in late sepsis. Adoptive transfer of early (day 3) MDSCs from septic mice into naive mice after CLP increased proinflammatory cytokine production, decreased peritoneal bacterial growth, and increased early mortality. Conversely, transfer of late (day 12) MDSCs from septic mice had the opposite effects. Early and late MDSCs studiedex vivoalso differed in their inflammatory phenotypes. Early MDSCs expressed nitric oxide and proinflammatory cytokines, whereas late MDSCs expressed arginase activity and anti-inflammatory interleukin 10 (IL-10) and transforming growth factor β (TGF-β). Late MDSCs had more immature CD31+myeloid progenitors and, when treatedex vivowith granulocyte-macrophage colony-stimulating factor (GM-CSF), generated fewer macrophages and dendritic cells than early MDSCs. We conclude that as the sepsis inflammatory process progresses, the heterogeneous MDSCs shift to a more immature state and from being proinflammatory to anti-inflammatory.

scholarly journals Flavonoids: Nutraceuticals for Rheumatic Diseases via Targeting of Inflammasome Activation

2021 ◽  
Vol 22 (2) ◽  
pp. 488
Author(s):  
Young-Su Yi
Keyword(s):  
Rheumatic Diseases ◽  
Fruits And Vegetables ◽  
Inflammatory Responses ◽  
Protein Complexes ◽  
Cellular Damage ◽  
Inflammatory Rheumatic Diseases ◽  
Inflammasome Activation ◽  
Central Feature ◽  
Inflammatory Protein ◽  
Anti Inflammatory

Inflammation, an innate immune response that prevents cellular damage caused by pathogens, consists of two successive mechanisms, namely priming and triggering. While priming is an inflammation-preparation step, triggering is an inflammation-activation step, and the central feature of triggering is the activation of inflammasomes and intracellular inflammatory protein complexes. Flavonoids are natural phenolic compounds predominantly present in plants, fruits, and vegetables and are known to possess strong anti-inflammatory activities. The anti-inflammatory activity of flavonoids has long been demonstrated, with the main focus on the priming mechanisms, while increasing numbers of recent studies have redirected the research focus on the triggering step, and studies have reported that flavonoids inhibit inflammatory responses and diseases by targeting inflammasome activation. Rheumatic diseases are systemic inflammatory and autoimmune diseases that primarily affect joints and connective tissues, and they are associated with numerous deleterious effects. Here, we discuss the emerging literature on the ameliorative role of flavonoids targeting inflammasome activation in inflammatory rheumatic diseases.

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