C1QTNF6 participates in the pathogenesis of PCOS by affecting the inflammatory response of granulosa cells

2021 ◽  
Author(s):  
Sisi Yan ◽  
Jinli Ding ◽  
Yi Zhang ◽  
Jiayu Wang ◽  
Sainan Zhang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mouse Models ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Low Grade ◽  
Reactive Protein ◽  
Reproductive Endocrine ◽  
Factor Α

Abstract Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease. It has been reported that chronic low-grade inflammation might participate in its pathogenesis. C1q and TNF related 6 (C1QTNF6) is a newly identified adiponectin paralog associated with inflammation. The aim of the present study was to investigate the role of C1QTNF6 in the development of chronic inflammation in PCOS and the underlying molecular mechanism. After analyzing the expression of C1QTNF6 in the serum and granulosa cells (GCs) of PCOS patients and healthy controls, we verified the roles of C1QTNF6 in inflammation through dehydroepiandrosterone-induced PCOS mouse models and cell models of lipopolysaccharide (LPS)-induced inflammation. The results demonstrated that C1QTNF6 expression in the serum and GCs of patients with PCOS was significantly elevated compared with those of the controls, and similar results were observed in the serum and ovary of PCOS mouse models. In PCOS mice and C1QTNF6-overexpressing PCOS mice, serum levels of pro-inflammatory factors including C-reactive protein (CRP), interleukin 6 (IL6) and tumor necrosis factor-α (TNFα) were increased, while the opposite effects were observed when C1QTNF6 was downregulated in PCOS mice. Furthermore, C1QTNF6 overexpression upregulated the levels of TNFα, IL6, and CRP and activated the AKT/NF-κB pathway in LPS-treated KGN cells, whereas C1QTNF6 knockdown and BAY-117082 (an NF-κB inhibitor) treatment resulted in the opposite effects. Taken together, our results indicate that C1QTNF6 is involved in the pathogenesis of PCOS by affecting the inflammatory response via the AKT/NF-κB signaling pathway.

Genetic Variation in TNF-α, its Relation with Inflammatory Biomarkers and Susceptibility to Rheumatoid Arthritis

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Khadiga Ahmed Ismail
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Level ◽  
Functional Disability ◽  
Serum Levels ◽  
Amplification Refractory Mutation System ◽  
Reactive Protein ◽  
Tnf Α ◽  
Mutation System ◽  
Potential Factor ◽  
Factor Α

Background: Tumor necrosis Factor-α (TNF-α) is encoded and controlled by TNF-α gene, which is involved in rheumatoid arthritis (RA) susceptibility. This research aimed to identify genetic variations of TNF-α (G308A) and to establish its association with inflammatory markers in Rheumatoid Arthritis predisposition. Methods: In the present study, fifty RA patients and fifty volunteers were involved and evaluated for the C-reactive protein, rheumatoid factor, and TNF-α were estimated by ELISA, Erythrocyte Sedimentation Rate (ESR) by Wintergreen method and for TNF-α-308 G>A polymorphism by polymerase chain reaction with amplification refractory mutation system (PCR-ARMS). Results: The CRP, RF, ESR and TNF-α were significantly elevated in RA patients relative to controls. The serum level TNF-α was also significantly elevated in female patients and in patients ≥50 years. Analysis of TNF-308 gene polymorphism revealed that GG genotypes were more prevalent in RA patients than in the healthy individuals and that GG genotype may be a potential factor to RA. The G allele was more common in RA than in the control. Elevated TNF-α serum levels were significantly associated the GG genotype and functional disability in RA patients. Conclusion: TNF-α promoter 308polymorphism GG genotype may be considered as a risk factor for RA and the TNF-α serum level was significantly related to the functional disability in the disease.

scholarly journals PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiayu Huang ◽  
Lin Liu ◽  
Chunyan Chen ◽  
Ying Gao
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary ◽  
Predictive Biomarker ◽  
Normal Weight ◽  
Inflammatory Factors ◽  
Low Grade ◽  
Model Assessment ◽  
Increased Risk ◽  
Homeostatic Model Assessment ◽  
Low Grade Inflammation

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, and its pathogenesis is still under debate. Trimethylamine-N-oxide (TMAO) is a small, organic compound generated by the gut microbiome with a hypothesized relation to insulin resistance (IR) and low-grade inflammation in PCOS. By comparing plasma TMAO levels in non-PCOS participants and PCOS patients without hyperandrogenism (HA), we aimed to determine whether plasma TMAO levels correlate with PCOS without HA and to analyze their relationship with low-grade inflammation and IR. Methods A total of 27 PCOS patients without HA and 23 non-PCOS participants were enrolled in this study and subdivided into “nonobese” and “obese” arms for each group. Levels of plasma TMAO were quantified, and basic clinical characteristics and plasma biomarkers of inflammation were assessed. Results First, plasma TMAO levels, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values were higher in PCOS patients without HA, especially in the obese subgroup. Second, the levels of the inflammatory factors interleukin (IL)-17A, IL-18 and interferon gamma (IFN-γ) were significantly increased in obese PCOS patients without HA. Third, plasma TMAO levels were associated with body mass index (BMI) in the normal-weight groups, and the obese groups had higher fasting plasma insulin (FINS) and HOMA-IR values. Finally, logistic regression showed that the plasma levels of TMAO and luteinizing hormone/follicle-stimulating hormone (LH/FSH) were independent predictors of PCOS and indicated an increased risk of PCOS. Conclusions Elevated plasma TMAO levels may be associated with the pathogenesis of PCOS without HA and correlated with increased systemic inflammation. Further studies are needed to determine the suitability of TMAO as a predictive biomarker and to identify possible therapies for PCOS.

scholarly journals Inflammatory and immunogenetic markers in correlation with pulmonary tuberculosis

2013 ◽  
Vol 39 (6) ◽  
pp. 719-727 ◽  
Author(s):  
Beatriz Lima Alezio Muller ◽  
Daniela Maria de Paula Ramalho ◽  
Paula Fernanda Gonçalves dos Santos ◽  
Eliene Denites Duarte Mesquita ◽  
Afranio Lineu Kritski ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Pulmonary Tuberculosis ◽  
Gene Polymorphisms ◽  
Serum Levels ◽  
Acute Inflammatory Response ◽  
Reactive Protein ◽  
Antituberculosis Treatment ◽  
Tnf Α ◽  
Referral Hospitals ◽  
Ifn Γ

OBJECTIVE: To describe serum levels of the cytokines IL-10, TNF-α, and IFN-γ, as well as polymorphisms in the genes involved in their transcription, and their association with markers of the acute inflammatory response in patients with pulmonary tuberculosis.METHODS: This was a descriptive, longitudinal study involving 81 patients with pulmonary tuberculosis treated at two referral hospitals. We collected data on sociodemographic variables and evaluated bacteriological conversion at the eighth week of antituberculosis treatment, gene polymorphisms related to the cytokines studied, and serum levels of those cytokines, as well as those of C-reactive protein (CRP). We also determined the ESR and CD4+ counts.RESULTS: The median age of the patients was 43 years; 67 patients (82.7%) were male; and 8 patients (9.9%) were infected with HIV. The ESR was highest in the patients with high IFN-γ levels and low IL-10 levels. IFN-γ and TNF-α gene polymorphisms at positions +874 and −238, respectively, showed no correlations with the corresponding cytokine serum levels. Low IL-10 levels were associated with IL-10 gene polymorphisms at positions −592 and −819 (but not −1082). There was a negative association between bacteriological conversion at the eighth week of treatment and CRP levels.CONCLUSIONS: Our results suggest that genetic markers and markers of acute inflammatory response are useful in predicting the response to antituberculosis treatment.

Investigation of the inflammatory biomarkers of metabolic syndrome in adolescents

2016 ◽  
Vol 0 (0) ◽  
Author(s):  
Ummugulsum Can ◽  
Muammer Buyukinan ◽  
Asuman Guzelant ◽  
Ayse Ugur ◽  
Adnan Karaibrahimoglu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Syndrome ◽  
Serum Levels ◽  
Inflammatory Biomarkers ◽  
Low Grade ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Hs Crp ◽  
Age And Sex

AbstractBackground:Metabolic syndrome (MetS) is a chronic and multifactorial syndrome characterized by a low-grade chronic inflammation, and a major risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In our study, we aimed to investigate the serum levels of high sensitive C-reactive protein (hs-CRP), haptoglobin (Hp), αMethods:This study was performed in 43 (18 males, 25 females) MetS adolescents between the ages of 13 and 17 years (14.70±1.15) and 43 lean controls were matched for age and sex. The serum levels of Hp, αResults:Serum Hp, fetuin-A (p<0.01) and PF-4, hs-CRP, SAP, AGP (p<0.001) values of the MetS subjects were significantly higher than those of the controls. No difference was found in serum αConclusions:This finding suggests the possibility of using these markers in diagnosis of MetS in adolescents to prevent future complications.

scholarly journals Effects of metformin treatment on serum levels of C-reactive protein and interleukin-6 in women with polycystic ovary syndrome

Medicine ◽  
2017 ◽  
Vol 96 (39) ◽  
pp. e8183 ◽  
Author(s):  
Jiao Wang ◽  
Lingyan Zhu ◽  
Kaixiang Hu ◽  
Yunliang Tang ◽  
Xiangxia Zeng ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Interleukin 6 ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Metformin Treatment ◽  
C Reactive Protein ◽  
Ovary Syndrome ◽  
Reactive Protein

scholarly journals Effects of budesonide and probiotics enemas on the systemic inflammatory response of rats with experimental colitis

2007 ◽  
Vol 22 (suppl 1) ◽  
pp. 40-45 ◽  
Author(s):  
Mardem Machado de Souza ◽  
José Eduardo de Aguilar-Nascimento ◽  
Diana Borges Dock-Nascimento
Keyword(s):  
Inflammatory Response ◽  
Experimental Colitis ◽  
Serum Levels ◽  
Systemic Inflammatory Response ◽  
Control Group ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Inflammatory Status ◽  
Male Wistar Rats ◽  
Group 5

PURPOSE: The aim of this study was to investigate the effect of enemas containing probiotics and budesonide on the systemic inflammatory response in experimental colitis. METHODS: Fifty male Wistar rats with experimental colitis induced by 10% acetic acid enema were randomized to five groups (10 rats each) according to the treatment: group 1 - saline solution, group 2 - budesonide (0.75 mg/kg/day), group 3 - probiotics (1mg/day), group 4 - probiotics plus budesonide, and group 5 - control, with not-treated rats. The following variables were studied: body weight, serum levels of albumin, C-reactive protein and interleucine-6 (IL-6). RESULTS: All animals lost weight between the beginning and the end of the experiment (280+ 16 mg versus 249+21 mg, p< 0.001). There was a significant decrease in the serum albumin between the normal pre-induction level (3.45 + 0.49mg/dL) and the 1st day after colitis induction (1.61+051mg/dL, p< 0.001) in all treated groups when compared to the control group. C- reactive protein increased after induction and diminished on the 7th day in all groups. In the control group there was an increase in the IL-6 after colitis induction. None of the treated groups significantly differed from IL-6 pre-colitis status (p>0.05). Only probiotic rats presented a significant decrease of IL-6 than controls (0,30±0,08 mg/dL vs. 0,19±0,03 mg/dL; p<0.01). CONCLUSION: Probiotic associated with budesonida Probiotics are effective to diminished inflammatory status mediated by IL-6 in experimental colitis.

scholarly journals Systemic Inflammation and Clinical Outcomes in COVID-19: a retrospective study

2020 ◽  
Author(s):  
Meijia Wang ◽  
Zhenli Huang ◽  
Kun Tang ◽  
Pengfei Gao ◽  
Yanjiao Lu ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Clinical Outcomes ◽  
Systemic Inflammation ◽  
Trial Registration ◽  
Inflammatory Factors ◽  
Reactive Protein ◽  
Tnf Α ◽  
Registration Number ◽  
Factor Α

Abstract Background：COVID-19 causes epidemics and pandemics worldwide, but the role of pathophysiological parameters particularly systemic inflammation in COVID-19 has not been understood. We aimed to investigate clinical outcomes in view of systemic inflammation in COVID-19.Methods：In this retrospective study, the demographic and clinical data of 225 confirmed COVID-19 cases on admission at Tongji Hospital from January 28 to February 15, 2020, were extracted and analyzed. These patients were categorized by inflammation state on the basis of the expression of inflammatory factors or classified as severe and non-severe according to 2019 American Thoracic Society / Infectious Disease Society of America guidelines.Results: Among 225 patients with confirmed COVID-19, 155 patients (68.9%) categorized into hyperinflammation group and 70 (31.1%) were non- hyperinflammation group. Compared to non-hyperinflammation group, hyperinflammation group more frequently had chest tightness/dyspnea and lymphopenia, aberrant multiple indexes of organ function including the heart, liver, kidney, and coagulation, with higher level of C-reactive protein (hsCRP) as well as interleukin (IL)-6, IL-8, tumour necrosis factor α (TNF-α), etc. Hyperinflammation group were more likely to admit to intensive care unit (ICU) (52.3% vs 5.7%), receive ventilation (84.5% vs 10.0%) and be with higher mortality (44.5% vs 5.7%) than non-hyperinflammation group. The mortality of severe patients with hyperinflammation (60/99, 60.6%) was significantly higher than without hyperinflammation (2/20, 10.0%). Non-severe patients with hyperinflammation even tended to have higher mortality (9/56, 16.1%) than those in severe cases without hyperinflammation (2/20, 10%).Conclusion: Excessive systemic inflammation was correlated highly with poor clinical outcomes in COVID-19, particularly in severe cases. Non-severe patients with hyperinflammation even tended to have higher mortality than those in severe cases without hyperinflammation.Trial registration: This is a retrospective observational study without a trial registration number.

The Role of Serum Procalcitonin and Interleukin-6 in the Differentiation and Surveillance of Sepsis and Non-Infectious Systemic Inflammatory Response Syndrome.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3792-3792 ◽  
Author(s):  
Xiaoli Liu ◽  
Bin Du ◽  
Jiaqi Pan ◽  
Baolai Hua
Keyword(s):  
Length Of Stay ◽  
Inflammatory Response ◽  
Interleukin 6 ◽  
Serum Levels ◽  
Serum Concentrations ◽  
Receiver Operating Characteristic Curves ◽  
Reactive Protein ◽  
Clinical Onset ◽  
Icu Length Of Stay

Abstract To evaluate the discrimination of serum procalcitonin (PCT) and interleukin-6 (IL-6) between patients with sepsis and non-infectious inflammatory response syndrome (SIRS) and the pridicton power of clinical outcome, a perspective study was performed in 27 patients with sepsis and 30 patients with non-infectious SIRS. The serum concentrations of PCT, IL-6, and C-reactive protein (CRP), white blood cell count, percentage of neutrophil, and maximal body temperature were obtained less than 24 hours after clinical onset of SIRS. The serum levels of PCT and IL-6, and percentage of neutrophil were significantly higher in patients of sepsis than in those of SIRS (PCT 5.54 [1.20, 32.74] μg/L vs 0.77 [0.22, 3.90] μg/L, P=0.001; IL-6 163.66 [33.60, 505.26] ng/L vs 37.72 [22.52,110.78] ng/L, P=0.004; CRP 15.28±8.41 g/L vs 9.51±7.65 g/L, P=0.010; and percentage of neutrophil 91%±4% vs 88%±4%, P=0.010). Receiver operating characteristic curves showed that the power of PCT and IL-6 were the best of all above. There was significant correlation between serum concentrations of PCT or IL-6 and the APACHE II or SOFA score, so was between serum PCT concentration and the ICU length of stay. Serum concentrations of PCT and IL-6 are more reliable indicators to differentiate sepsis and non-infectious SIRS than the conventional inflammatory markers, and correlate with the disease severity. And PCT levels were significantly correlated with ICU length of stay. (Supported by research grants from PUMCH, China)

scholarly journals Chronic Low Grade Inflammation in Pathogenesis of PCOS

2021 ◽  
Vol 22 (7) ◽  
pp. 3789
Author(s):  
Ewa Rudnicka ◽  
Katarzyna Suchta ◽  
Monika Grymowicz ◽  
Anna Calik-Ksepka ◽  
Katarzyna Smolarczyk ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Polycystic Ovary Syndrome ◽  
Chronic Inflammation ◽  
Polycystic Ovary ◽  
Low Grade ◽  
C Reactive Protein ◽  
Ovary Syndrome ◽  
Gene Markers ◽  
Reactive Protein ◽  
Inflammatory State

Polycystic ovary syndrome (PCOS) is a one of the most common endocrine disorders, with a prevalence rate of 5–10% in reproductive aged women. It’s characterized by (1) chronic anovulation, (2) biochemical and/or clinical hyperandrogenism, and (3) polycystic ovarian morphology. PCOS has significant clinical implications and can lead to health problems related to the accumulation of adipose tissue, such as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. There is also evidence that PCOS patients are at higher risk of cardiovascular diseases, atherosclerosis, and high blood pressure. Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation. According to known data, inflammatory markers or their gene markers are higher in PCOS patients. Correlations have been found between increased levels of C-reactive protein (CRP), interleukin 18 (IL-18), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), white blood cell count (WBC), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) in the PCOS women compared with age- and BMI-matched controls. Women with PCOS present also elevated levels of AGEs and increased RAGE (receptor for advanced glycation end products) expression. This chronic inflammatory state is aggravating by obesity and hyperinsulinemia. There are studies describing mutual impact of hyperinsulinemia and obesity, hyperandrogenism, and inflammatory state. Endothelial cell dysfunction may be also triggered by inflammatory cytokines. Many factors involved in oxidative stress, inflammation, and thrombosis were proposed as cardiovascular risk markers showing the endothelial cell damage in PCOS. Those markers include asymmetric dimethylarginine (ADMA), C-reactive protein (CRP), homocysteine, plasminogen activator inhibitor-I (PAI-I), PAI-I activity, vascular endothelial growth factor (VEGF) etc. It was also proposed that the uterine hyperinflammatory state in polycystic ovary syndrome may be responsible for significant pregnancy complications ranging from miscarriage to placental insufficiency. In this review, we discuss the most importance evidence concerning the role of the process of chronic inflammation in pathogenesis of PCOS.

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