The Inflammasome Contributes to Depletion of the Ovarian Reserve During Aging in Mice

Ovarian aging is a natural process characterized by follicular depletion and a reduction in oocyte quality, resulting in loss of ovarian function, cycle irregularity and eventually infertility and menopause. The factors that contribute to ovarian aging have not been fully characterized. Activation of the NLRP3 inflammasome has been implicated in age-associated inflammation and diminished function in several organs. In this study, we used Asc−/− and Nlrp3−/− mice to investigate the possibility that chronic low-grade systemic inflammation mediated by the inflammasome contributes to diminished ovarian reserves as females age. Pro-inflammatory cytokines, IL-6, IL-18, and TNF-α, were decreased in the serum of aging Asc−/− mice compared to WT. Within the ovary of reproductively aged Asc−/− mice, mRNA levels of major pro-inflammatory genes Tnfa, Il1a, and Il1b were decreased, and macrophage infiltration was reduced compared to age-matched WT controls. Notably, suppression of the inflammatory phenotype in Asc−/− mice was associated with retention of follicular reserves during reproductive aging. Similarly, the expression of intra-ovarian pro-inflammatory cytokines was reduced, and follicle numbers were significantly elevated, in aging Nlrp3−/− mice compared to WT controls. These data suggest that inflammasome-dependent inflammation contributes to the age-associated depletion of follicles and raises the possibility that ovarian aging could be delayed, and fertile window prolonged, by suppressing inflammatory processes in the ovary.

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Anti-inflammatory effect of piperine ameliorates insulin resistance in monosodium glutamate–treated obese mice

10.21203/rs.3.rs-16723/v1 ◽

2020 ◽

Author(s):

Chaolong Liu ◽

Yanting Yuan ◽

Ji Zhou ◽

Ruixin Hu ◽

Lixia Ji ◽

...

Keyword(s):

Insulin Resistance ◽

Inflammatory Cytokines ◽

Monosodium Glutamate ◽

Oral Glucose ◽

Low Grade ◽

Mrna Levels ◽

Obese Mice ◽

Adipose Tissues ◽

Metabolic Inflammation ◽

Pro Inflammatory Cytokines

Abstract Background: Metabolic inflammation has been considered as an essential event in obesity-induced diabetes and insulin resistance. In obesity, an increasing number of macrophages recruited into visceral adipose tissues undergo significant M 1 -like polarization, secreting variable amounts of pro-inflammatory cytokines and causing insulin resistance. Methods: In this study, we investigated the effect of piperine on adipose tissue inflammation and insulin resistance in monosodium glutamate (MSG)-induced obese mice. The 6-month-old MSG mice were divided into three groups, which were treated with piperine (40 mg/kg/day), metformin (150 mg/kg/day) and vehicle for successive 10 weeks, respectively. Normal mice at the same age as the normal control. Results: Our results showed that the 10-week administration of piperine (40 mg/kg/d) not only significantly decreased the elevated fasting blood glucose, serum TC and TG levels, but also enhanced infusion rate in hyperglycemic clamp experiment and improved the oral glucose intolerance as well as abnormal insulin tolerance in adult MSG obese mice. Additionally, piperine significantly decreased the total and differential white blood cell (WBC) count and the serum level of lipopolysaccharide (LPS), pro-inflammatory cytokines such as galectin-3 (Gal-3), interleukin-1β (IL-1β). Furthermore, piperine clearly down-regulated the mRNA levels of pro-inflammatory cytokines and the protein levels of CD11c and Gal-3 in adipose tissues. In addition, the in vitro study showed that piperine inhibited LPS- stimulated polarization of RAW 264.7 cells toward the M 1 phenotype. Conclusions: In summary, these findings demonstrated that piperine could significantly rectify glycolipid metabolism disorders, improve severe insulin resistance and ameliorates systemic metabolic inflammation in MSG obesity mice. Our study indicates that piperine, as a potential natural alkaloid, can be used in the treatment of obesity-associated diabetes by delaying the progression of obesity-induced insulin resistance. Keywords : Insulin resistance; Piperine; Chronic low-grade inflammation.

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Evaluation of the role of CD47 in sickle cell disease

Journal of Hematopathology ◽

10.1007/s12308-020-00433-5 ◽

2021 ◽

Author(s):

Basmah Eldakhakhny ◽

Hadeel Al Sadoun ◽

Nehal Bin Taleb ◽

Dunya Ahmed Nori ◽

Nawal Helmi ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Annexin V ◽

Cell Disease ◽

Phagocytic Cells ◽

Surface Marker Expression ◽

Inflammatory Phenotype ◽

Healthy Control ◽

Cell Surface Marker Expression ◽

Pro Inflammatory Cytokines

AbstractCD47 is a self-marker expressed on the surface of RBCs and work to prevent the process of phagocytosis. SIRPα is the ligand of CD47 that is expressed on the surface of phagocytic cells, such as macrophages, to control the removal of dead/diseased cells. This study aimed to examine the expression of CD47 on RBCs and SIRPα on PBMC cells in SCD patients and the apoptosis of SCD RBCs. We also measured the levels of pro-inflammatory cytokines in SCD patients and correlated it with the cell surface marker expression of CD47 and SIRPα to determine whether CD47 and/or SIRPα played a role in promoting the pro-inflammatory phenotype in SCD. Whole blood samples were drawn from SCD patients, and healthy control and PBMC were isolated and stained with SIRPα. Change in CD47, apoptosis by annexin V marker, and pro-inflammatory cytokines were measured and correlation among these variants was determined. The expression of CD47 was significantly decreased and the apoptosis was increased in RBCs of SCD patients. A higher level of pro-inflammatory cytokines, IL-6 and IL-1β, was found in SCD patients and IL-1β was found to be inversely correlated with SIRPα expression. Our data showed that CD47 of erythrocytes of SCD samples is reduced and that the apoptosis is increased in those patients. Based on the role of CD47, we suggest that increased apoptosis in SCD would be impacted by the reduced level of CD47. An inverse relationship was found between SIRPα marker on PBMC and the increased production of pro-inflammatory cytokines in SCD.

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Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study

Endocrine ◽

10.1007/s12020-021-02807-w ◽

2021 ◽

Author(s):

Francesca Coperchini ◽

Gianluca Ricci ◽

Laura Croce ◽

Marco Denegri ◽

Rubina Ruggiero ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Combination Treatment ◽

Primary Cultures ◽

Human Thyroid ◽

Thyroid Cell ◽

Mrna Levels ◽

Thyroid Cells ◽

Tnf Α ◽

Ifn Γ ◽

Pro Inflammatory Cytokines

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.

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Establishment of a Mouse Model of Premature Ovarian Failure Using Consecutive Superovulation

Cellular Physiology and Biochemistry ◽

10.1159/000495895 ◽

2018 ◽

Vol 51 (5) ◽

pp. 2341-2358 ◽

Cited By ~ 4

Author(s):

Xiaowei Nie ◽

Youjin Dai ◽

Yuan Zheng ◽

Dan Bao ◽

Qin Chen ◽

...

Keyword(s):

Mouse Model ◽

Premature Ovarian Failure ◽

Cell Apoptosis ◽

Quantitative Polymerase Chain Reaction ◽

Oocyte Quality ◽

Ovarian Failure ◽

Control Group ◽

Mrna Levels ◽

Primordial Follicles ◽

Ovarian Aging

Background/Aims: This study investigated the effect of consecutive superovulation on the ovaries and established a premature ovarian failure (POF) model in mice. Methods: The mouse POF model was induced by 5-15 consecutive superovulation treatments with pregnant mare serum gonadotropin (PMSG), human chorionic gonadotropin (HCG) and prostaglandin F2α (PGF2α). Normal adult mice were compared with mice displaying natural ovarian aging. The following serum biochemical parameters were measured: including follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), inhibin B (INH B), malondialdehyde (MDA), total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. Follicles were counted using H&E staining. Levels of 8-hydroxyguanosine (8-OhdG), 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), anti-Mullerian hormone (AMH) and CDKN2A/ p16 (p16) were detected using immunohistochemical staining. Reactive oxygen species (ROS) levels were measured using dihydroethidium (DHE) staining. Cell apoptosis was detected using an in situ TUNEL fluorescence staining assay. Levels of proteins involved in ROS-related pathways and the p16 protein were detected using Western blotting. Sod1, Sod2 and Sod3 mRNA levels were detected using quantitative polymerase chain reaction (Q-PCR). Oocyte quality was evaluated using in vitro fertilization (IVF) and zygote culture. Results: Consecutive superovulation groups presented lower P, E2, SOD, GSH-Px and INH B levels, significantly higher FSH, LH, MDA and ROS levels, and significantly fewer primordial follicles compared with the control group. Consecutive superovulation groups presented significantly increased levels of Sod2, 8-OhdG, 4-HNE, NTY, significantly increased levels of the SIRT1 and FOXO1 proteins, significantly increased levels of the senescence-associated protein p16, as well as decreased AMH, Sod1 and Sod3 levels and increased granulosa cell apoptosis compared with the control group. Conclusion: Consecutive superovulation significantly decreased ovarian function and oocyte quality and increased oxidative stress and apoptosis in the ovary via a mechanism involving the p16 and SIRT1/FOXO1 signaling pathways. These findings suggest that consecutive superovulation may be used to establish a mouse model of ovarian aging.

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Spirulina Lipids Alleviate Oxidative Stress and Inflammation in Mice Fed a High-Fat and High-Sucrose Diet

Marine Drugs ◽

10.3390/md18030148 ◽

2020 ◽

Vol 18 (3) ◽

pp. 148 ◽

Cited By ~ 3

Author(s):

Yuhong Yang ◽

Lei Du ◽

Masashi Hosokawa ◽

Kazuo Miyashita

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

Lipid Hydroperoxide ◽

Mrna Levels ◽

High Fat ◽

Inflammatory Status ◽

Sucrose Diet ◽

High Sucrose Diet ◽

High Sucrose ◽

Pro Inflammatory Cytokines

High-fat and high-sucrose diet (HFHSD)-induced obesity leads to oxidative stress and chronic inflammatory status. However, little is known about the beneficial effects of total lipids extracted from Spirulina. Hence, in the present study, Spirulina lipids were extracted with chloroform/methanol (SLC) or ethanol (SLE) and then their effects on oxidative stress and inflammation in the mice fed a HFHSD were investigated. The results show that the major lipid classes and fatty acid profiles of SLC and SLE were almost similar, but the gamma-linolenic acid (GLA) and carotenoid contents in SLE was a little higher than that in SLC. Dietary 4% SLC or SLE for 12 weeks effectively decreased the hepatic lipid hydroperoxide levels as well as increased the activities and mRNA levels of antioxidant enzymes in the mice fed a HFHSD. In addition, supplementation with SLC and SLE also markedly decreased the levels of serum pro-inflammatory cytokines and the mRNA expression of pro-inflammatory cytokines in the liver and epididymal white adipose tissue of mice fed a HFHSD, and the effects of SLC and SLE were comparable. These findings confirm for the first time that dietary Spirulina lipids could alleviate HFHSD-induced oxidative stress and inflammation.

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Alzheimer's disease and periodontitis - an elusive link

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.60.02.015 ◽

2014 ◽

Vol 60 (2) ◽

pp. 173-180 ◽

Cited By ~ 16

Author(s):

Abhijit N. Gurav

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Inflammatory Cytokines ◽

Critical Role ◽

Anaerobic Bacteria ◽

Systemic Infection ◽

Low Grade ◽

Inflammatory Status ◽

Pro Inflammatory Cytokines

Alzheimer's disease is the preeminent cause and commonest form of dementia. It is clinically characterized by a progressive descent in the cognitive function, which commences with deterioration in memory. The exact etiology and pathophysiologic mechanism of Alzheimer's disease is still not fully understood. However it is hypothesized that, neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease. Alzheimer's disease is marked by salient inflammatory features, characterized by microglial activation and escalation in the levels of pro-inflammatory cytokines in the affected regions. Studies have suggested a probable role of systemic infection conducing to inflammatory status of the central nervous system. Periodontitis is common oral infection affiliated with gram negative, anaerobic bacteria, capable of orchestrating localized and systemic infections in the subject. Periodontitis is known to elicit a "low grade systemic inflammation" by release of pro-inflammatory cytokines into systemic circulation. This review elucidates the possible role of periodontitis in exacerbating Alzheimer's disease. Periodontitis may bear the potential to affect the onset and progression of Alzheimer's disease. Periodontitis shares the two important features of Alzheimer's disease namely oxidative damage and inflammation, which are exhibited in the brain pathology of Alzheimer's disease. Periodontitis can be treated and hence it is a modifiable risk factor for Alzheimer's disease.

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Escin Increases the Survival Rate of LPS-Induced Septic Mice Through Inhibition of HMGB1 Release from Macrophages

Cellular Physiology and Biochemistry ◽

10.1159/000430320 ◽

2015 ◽

Vol 36 (4) ◽

pp. 1577-1586 ◽

Cited By ~ 14

Author(s):

Yajun Cheng ◽

Hongrui Wang ◽

Min Mao ◽

Chao Liang ◽

Yu Zhang ◽

...

Keyword(s):

Survival Rate ◽

Western Blot ◽

Inflammatory Cytokines ◽

Molecular Mechanisms ◽

Post Treatment ◽

Mrna Levels ◽

Treatment Methods ◽

Protein Levels ◽

Qrt Pcr ◽

Pro Inflammatory Cytokines

Background: Previous studies have described the effects of Escin on improving the survival rate of endotoxemic animals. The purpose of this study was to explore the molecular mechanisms of this potentially beneficial treatment. Methods: First, the survival rate of endotoxemic mice was monitored for up to 2 weeks after Escin pretreatment, Escin post-treatment, or Escin post-treatment + rHMGB1. The effects of Escin on the release of pro-inflammatory cytokines such as TNF-a, IL-1ß, IL-6 and HMGB1 in the serum of endotoxemic mice and LPS-induced macrophages were evaluated by ELISA. Furthermore, the mRNA and protein levels of HMGB1 in LPS-induced macrophages were measured by qRT-PCR and Western blot, respectively. Additionally, the release of pro-inflammatory cytokines such as TNF-a, IL-1ß, IL-6 was evaluated by ELISA in rHMGB1-induced macrophages. Finally, the protein levels and the activity of NF-κB in macrophages were checked by Western blot and ELISA, respectively. Results: Both pretreatment and post-treatment with Escin could improve the survival rate of endotoxemic mice, while exogenous rHMGB1 reversed this effect. In addition, Escin decreased the level of the pro-inflammatory cytokines TNF-a, IL-1ß, IL-6 and HMGB1 in endotoxemic mice and in LPS-induced macrophages. Escin could also inhibit the mRNA levels and activity of HMGB1. The release of the pro-inflammatory cytokines TNF-a, IL-1ß, IL-6 could be suppressed in rHMGB1-induced macrophages by Escin. Finally, Escin could suppress the activation of NF-κB in LPS-induced macrophages. Conclusion: Escin could improve the survival of mice with LPS-induced endotoxemia. This effect maybe meditated by reducing the release of HMGB1, resulting in the suppression of the release of pro-inflammatory cytokines.

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Pro-Inflammatory Cytokines as Potential Early Biomarkers and Therapeutic Targets to Combat Ischemic Stroke

Biotechnology Kiosk ◽

10.37756/bk.20.2.11.1 ◽

2020 ◽

Vol 2 (11) ◽

pp. 5-19

Author(s):

Megha Agrawal ◽

Keyword(s):

Ischemic Stroke ◽

Inflammatory Cytokines ◽

Time Window ◽

Medical Condition ◽

Brain Area ◽

Therapeutic Targets ◽

Ongoing Research ◽

Stroke Research ◽

Inflammatory Processes ◽

Pro Inflammatory Cytokines

Ischemic stroke is a serious medical condition and widely considered one of the most common causes of death and disability in the world today. There have been notable research advances in stroke so far and studies have shown that stroke’s complex pathophysiology process involves the oxidative stress and inflammatory reaction. However, despite the progress in stroke research, currently there are no established biochemical factors available that can be employed in the early diagnostics and intervention in stroke. Mostly, stroke diagnosis is based on neuroimaging, which is not a rapid tool to diagnose stroke. This decreases the survivability rate. Further, conventional therapeutic approaches for ischemic stroke management are based on restoring blood flow to the affected brain area and these therapies are effective only during a limited time window. Hence, this procedure results in benefiting only a very small percentage of patients. In view of these limitations, the ongoing research has focused on seeking alternative treatment methods that can reduce stroke brain damage and improve patients’ outcome. To this end, research goals are targeted towards gaining insights into the inflammatory response triggered by cerebral ischemia that is supposed to play an important role in the progression of stroke, and also the subsequent study of inflammatory molecules in the acute phase of stroke. In this mini-review, we describe the inflammatory processes occurring during ischemic stroke along with the potential for pro-inflammatory cytokines to become stroke biomarkers as well as interesting neuroprotective therapeutic targets that could be blocked or stimulated to modulate inflammation after stroke. Finally, we present a perspective briefly discussing some viewpoints on future studies in the ongoing field of stroke research.

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Ex Vivo Rumex Crispus and Cordyceps Sinensis Mixture Regulates Immune Cells Responses to Pro-inflammatory Cytokines inC57BL/6 mice Splenocytes

10.20944/preprints201807.0104.v1 ◽

2018 ◽

Cited By ~ 1

Author(s):

Eui-Seong Park ◽

Gyl-Hoon Song ◽

Seung-Min Lee ◽

Yong-Gyu Kim ◽

Kun-Young Park

Keyword(s):

Nitric Oxide ◽

Inflammatory Cytokines ◽

Immune Cells ◽

Cordyceps Sinensis ◽

No Production ◽

Mrna Levels ◽

Rumex Crispus ◽

Enhanced Production ◽

Cox 2 ◽

Pro Inflammatory Cytokines

We investigated the efficacy of a Rumex crispus and Cordyceps sinensis mixture made using the Beopje (Korea traditional processing method to remove anti-nutrients and enhance phytochemicals) method to regulate immune cell responses toward nitric oxide (NO) production, pro-inflammatory cytokines, and inflammation related genes in mice splenocytes. The six experimental groups were as follows: control (control), Rc-Cs (Rumex crispus (Rc) and Cordyceps sinensis (Cs) mixture, 6:4), TMC (Taemyeongcheong, commercial healthy drink containing Rc-Cs), LPS (lipopolysaccharide), LPS+Rc-Cs, and LPS+TMC. The Rc-Cs mixture reduced nitric oxide (NO) production in LPS-induced splenocytes. Moreover, Rc-Cs enhanced production of the pro-inflammatory cytokines TNF-α, IFN-γ, IL-1β, and IL-6 compared to the control (no treatment). However, Rc-Cs inhibited production of pro-inflammatory cytokines in LPS-induced splenocytes. In addition, LPS+Rc-Cs also significantly suppressed mRNA expression of IL-1β and IL-6 compared to LPS treatment. Interestingly, Rc-Cs did not increase mRNA levels of iNOS and COX-2, which are inflammation related genes compared to the control, while LPS+Rc-Cs reduced mRNA levels of iNOS and COX-2 compared LPS alone (p < 0.05). TMC showed a similar pattern compared to Rc-Cs. Therefore, Rc-Cs treatment in splenocytes enhanced NO production and pro-inflammatory cytokines compared to the control, whereas Rc-Cs treatment in LPS-induced splenocytes reduced NO production, pro-inflammatory cytokines, and inflammation related genes. Thus, Rc-Cs regulated immune cells responses by increasing pro-inflammatory cytokines in splenocytes and reducing toxin (LPS)-induced inflammation. These results indicate that a Rumex crispus and Cordyceps sinensis mixture (Rc-Cs) and TMC containing Rc-Cs promote immune cells responses and anti-inflammatory activities.

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COVID-19 and Obesity: Role of Ectopic Visceral and Epicardial Adipose Tissues in Myocardial Injury

Frontiers in Endocrinology ◽

10.3389/fendo.2021.726967 ◽

2021 ◽

Vol 12 ◽

Author(s):

Adèle Lasbleiz ◽

Bénédicte Gaborit ◽

Astrid Soghomonian ◽

Axel Bartoli ◽

Patricia Ancel ◽

...

Keyword(s):

Adipose Tissue ◽

Intensive Care ◽

Inflammatory Cytokines ◽

Visceral Adipose Tissue ◽

Cardiovascular Events ◽

Low Grade ◽

Viral Spread ◽

Visceral Adipose ◽

Pro Inflammatory Cytokines

In March 2020, the WHO declared coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic. Obesity was soon identified as a risk factor for poor prognosis, with an increased risk of intensive care admissions and mechanical ventilation, but also of adverse cardiovascular events. Obesity is associated with adipose tissue, chronic low-grade inflammation, and immune dysregulation with hypertrophy and hyperplasia of adipocytes and overexpression of pro-inflammatory cytokines. However, to implement appropriate therapeutic strategies, exact mechanisms must be clarified. The role of white visceral adipose tissue, increased in individuals with obesity, seems important, as a viral reservoir for SARS-CoV-2 via angiotensin-converting enzyme 2 (ACE2) receptors. After infection of host cells, the activation of pro-inflammatory cytokines creates a setting conducive to the “cytokine storm” and macrophage activation syndrome associated with progression to acute respiratory distress syndrome. In obesity, systemic viral spread, entry, and prolonged viral shedding in already inflamed adipose tissue may spur immune responses and subsequent amplification of a cytokine cascade, causing worse outcomes. More precisely, visceral adipose tissue, more than subcutaneous fat, could predict intensive care admission; and lower density of epicardial adipose tissue (EAT) could be associated with worse outcome. EAT, an ectopic adipose tissue that surrounds the myocardium, could fuel COVID-19-induced cardiac injury and myocarditis, and extensive pneumopathy, by strong expression of inflammatory mediators that could diffuse paracrinally through the vascular wall. The purpose of this review is to ascertain what mechanisms may be involved in unfavorable prognosis among COVID-19 patients with obesity, especially cardiovascular events, emphasizing the harmful role of excess ectopic adipose tissue, particularly EAT.

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