scholarly journals The balance of proinflammatory cytokines and Treg cells in chronic glomerulonephritis

2020 ◽  
Vol 92 (6) ◽  
pp. 46-52
Author(s):  
Natalya V. Chebotareva ◽  
Anatoly A. Vinogradov ◽  
Alla A. Gindis ◽  
Irina N. Bobkova ◽  
Wenjing Cao ◽  
...  

Chronic glomerulonephritis (CGN) is a disease with a steadily progressing course, which is based on inflammation with the activation of immune cells. The severity of the inflammatory reaction in the kidney tissue is determined by the balance of locally pro-inflammatory factors and protective mechanisms, which include anti-inflammatory cytokines and T-regulatory lymphocytes (Treg). The study of processes that can modulate the severity of inflammation in the kidney is of particular interest for understanding the basic patterns of CGN progression. Aim. To determine the clinical significance of the Th17, Th1, and Treg cytokines in urine to assess the activity and progression of chronic glomerulonephritis with nephrotic syndrome (NS). Materials and methods. The study included 98 patients with CGN 37 women and 61 men. Patients were divided into two groups according to the degree of CGN activity. Group I consisted of 51 patients with NS. In 21 subjects, a decrease in GFR60 ml/min was revealed. Group II included 47 patients with proteinuria from 1 to 3 g/day without NS. GFR60 ml/min/1.73 m2 was observed in 26 patients. A kidney biopsy was performed in 65 patients and the hystological diagnosis was verified: 20 had mesangioproliferative GN, 16 had membranous nephropathy, 18 had focal segmental glomerulosclerosis, and 11 had membranoproliferative GN. The control group consisted of 15 healthy people. The levels of IL-6, IL-10, IL-17, tumor necrosis factor a (TNF-a) in the urine were determined using enzyme-linked immunosorbent assay. The number of FoxP3-positive cells in the inflammatory interstitial infiltrate of the cortical layer was determined in 39 patients (in a biopsy sample in a 1.5 mm2 area). Results. In group of patients with CGN, there was an increase in the levels of Th17, Th1, and Treg cytokines in urine TNF-a and IL-10 compared with healthy individuals. An increase in the levels of IL-6 in the urine of patients with high clinical activity of CGN (with NS and renal dysfunction) was more pronounced than in patients with NS and normal renal function. There was a decrease in the number of Treg cells in the interstitium of the kidney and a decrease in the production of anti-inflammatory IL-10 in CGN patients with NS, compared with patients without NS. The most pronounced changes in the cytokine profile were observed in patients with FSGS with an increase in pro-inflammatory cytokines and a decrease in Treg in the kidney tissue/anti-inflammatory IL-10 in the urine. Conclusion. An imbalance of cytokines characterized by an increased levels of pro-inflammatory IL-17, IL-6, TNF-a, and a reduced levels of anti-inflammatory IL-10 and T-regulatory cells in the kidney tissue is noted in patients with NS, especially with FSGS. Imbalance of cytokines reflects the high activity of CGN and the risk of the progression of the disease.

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Somayeh Moradi ◽  
Vahid Nikoui ◽  
Muhammad Imran Khan ◽  
Shayan Amiri ◽  
Farahnaz Jazaeri ◽  
...  

Considering the cardioprotective and anti-inflammatory properties of clofibrate, the aim of the present experiment was to investigate the involvement of local and systemic inflammatory cytokines in possible antiarrhythmic effects of clofibrate in ouabain-induced arrhythmia in rats. Rats were orally treated with clofibrate (300 mg/kg), and ouabain (0.56 mg/kg) was administered to animals intraperitoneally. After induction of anesthesia, the atria were isolated and the onset of arrhythmia and asystole was recorded. The levels of inflammatory cytokines in atria were also measured. Clofibrate significantly postponed the onset of arrhythmia and asystole when compared to control group (P≤0.05andP≤0.01, resp.). While ouabain significantly increased the atrial beating rate in control group (P≤0.05), same treatment did not show similar effect in clofibrate-treated group (P>0.05). Injection of ouabain significantly increased the atrial and systemic levels of all studied inflammatory cytokines (P≤0.05). Pretreatment with clofibrate could attenuate the ouabain-induced elevation of IL-6 and TNF-αin atria (P≤0.01andP≤0.05, resp.), as well as ouabain-induced increase in IL-6 in plasma (P≤0.05). Based on our findings, clofibrate may possess antiarrhythmic properties through mitigating the local and systemic inflammatory factors including IL-6 and TNF-α.


2021 ◽  
Vol 55 (3) ◽  
pp. 131-141
Author(s):  
Vitaliy Shcherba ◽  
Inna Krynytska ◽  
Mariya Marushchak ◽  
Mykhaylo Korda

Abstract Objective. The aim of the present study was to investigate the presence of inflammatory mediators in rats with only periodontitis and periodontitis in a setting of hyper- and hypo-thyroidism and to analyze the correlative linkages between inflammatory mediators and thyroid hormones. Methods. White male 12–14 weeks old inbred rats (n=48) weighing 180–200 g were employed in the experiment. They were randomly divided into the following groups: Group I – control group, Group II – group with a model of periodontitis, Group III – group with a periodontitis in a setting of hyperthyroidism, and Group IV – group with periodontitis in a setting of hypothyroidism. The presence of tumor-necrosis factor-α (TNF-α) and interleukins IL-1β and IL-10 in the periodontal homogenate supernatant was studied by a solid-phase enzyme-linked immunosorbent assay. Results. It was shown that experimental lipopolysaccharide (LPS)-induced periodontitis is accompanied by hyperproduction of pro-inflammatory cytokines (TNF-α, IL-1β) and reduction of anti-inflammatory cytokines (IL-10), whereas TNF-α underwent to maximum changes. Thyroid dysfunction exacerbates cytokine imbalance and severity of inflammation in experimental LPS-induced periodontitis, especially pronounced at hyperthyroidism, as evidenced by the predominance of TNF-α and IL-1β levels in the periodontal homogenate supernatant by 38.5% (р<0.01) and 75.6% (p<0.001), respectively, hyperthyroid over the euthyroid, and by 20.1% (p<0.05) and 24.1% (p<0.05), respectively, over the hypothyroid rats. Conclusions. Thyroid dysfunction, especially hyperthyroidism, may play an important role in the pro-inflammatory response in periodontitis. Hyperproduction of inflammatory mediators in thyroid dysfunction can induce a noticeable damage in the whole apparatus of the periodontium, thereby causing progression of periodontitis.


2021 ◽  
Author(s):  
Mohammad Amin Mombeini ◽  
Hadi Kalantar ◽  
Elahe Sadeghi ◽  
Mehdi Goudarzi ◽  
Hamidreza Khalili ◽  
...  

Abstract Purpose Cyclophosphamide is an alkylating agent with nephrotoxicity that constraints its clinical application. Berberine is an isoquinoline derivative alkaloid with biological functions like antioxidant and anti-inflammatory. The current research intended to examine the nephroprotective impacts of berberine against cyclophosphamide-stimulated nephrotoxicity. Methods Forty animal subjects were randomly separated into five categories of control (Group I). Cyclophosphamide (200 mg/kg, i.p., on 7th day) (Group II), and groups III and IV that received berberine 50 and 100 mg/kg orally for seven days and a single injection of cyclophosphamide on 7th day. Group V as berberine (100 mg/kg, alone). On day 8, blood samples were drawn from the retro-orbital sinus to determine serum levels of blood urea nitrogen (BUN), creatinine (Cr), Neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) as biomarkers for kidney injury. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities as oxidative stress factors, tumor necrosis factor- α (TNF-α) and interleukin 1 beta (IL-1β) levels as inflammatory mediators were assessed in kidney tissue. Results The results of this study demonstrated that berberine was able to protect remarkably the kidney from CP-induced injury through decreasing the level of BUN, Cr, NGAL, KIM-1, NO, MDA TNF-α, IL-1β and increasing the level of GSH, CAT, SOD and GPx activities. Conclusion Berberine may be employed as a natural agent to prevent cyclophosphamide-induced nephrotoxicity through anti-oxidant and anti-inflammatory effects.


2020 ◽  
Vol 45 (2) ◽  
pp. 209-221 ◽  
Author(s):  
Ye Zhu ◽  
Sheng-Wei Wei ◽  
Ao Ding ◽  
Wei-Ping Zhu ◽  
Mei-Fang Mai ◽  
...  

Background/Aims: The purpose of this study is to analyze the expression and biological function of lncRNA ANRIL, microRNA-199a, TLR4, and nuclear factor-kappa B (NF-κB) in acute renal injury (AKI) induced by lipopolysaccharide (LPS). Methods: The levels of ANRIL and microRNA-199a in mouse cells and kidneys were detected by quantitative-polymerase chain reaction. Western blot analysis was used for the NF-κB pathway protein. MTT assay was used for cell viability. Enzyme-linked immunosorbent assay was used for the secretion of inflammatory factors in mouse kidney tissue. Apoptosis was measured by flow cytometry and Western blotting. The potential binding region between ANRIL and miR-199a was verified by luciferase reporter assay. Results: The upregulation of ANRIL can reduce the expression of microRNA-199a and increases the number of apoptotic cells. The expression levels of ANRIL in LPS-induced AKI mice and LPS-treated HK2 cells were upregulated compared with the control group. Overexpression of ANRIL increased apoptosis and promoted TLR4 (Toll-like receptor 4), NF-κB phosphorylation, and downstream transcription factor production. Conclusion: ANRIL/NF-κB pathway in LPS-induced apoptosis provided theoretical guidance for ANRIL in the treatment of AKI.


2021 ◽  
Vol 23 (4) ◽  
pp. 536-540
Author(s):  
O. M. Bilyi ◽  
N. A. Mitriaieva ◽  
M. V. Krasnoselskyi ◽  
L. V. Hrebinyk

Secondary edematous breast cancer (SEBC), T4b, has a poor prognosis. The aim of this study is to examine the balance in serum levels of pro-inflammatory (TNFά, IL-8) and anti-inflammatory (IL-4) cytokines in patients with SEBC before special treatment. Materials and methods. A total of 87 patients with breast cancer (BC) were examined before treatment: 42 patients with SEBC in T4bN0-3M0 stage and 45 BC patients in T3-4N1-3M0 stage without edema. The control group consisted of 15 patients with fibroadenomas. The serum levels of cytokines (IL-4, IL-8, TNFά) in the patients was determined using the enzyme-linked immunosorbent assay. Results. In the SEBC patients as compared to the patients without cancer, the serum pro-inflammatory cytokine (IL-8, TNFά) levels were significantly increased and the anti-inflammatory cytokine (IL-4) level was slightly increased in 22 %. In BC without edema, an imbalance was noted in favor of pro-inflammatory cytokines, but in SEBC it was more pronounced (31.6 versus 12.4 and 5.6 versus 3.2, respectively). Conclusions. In the majority of SEBC patients, there is an imbalance in the cytokine profile in favor of the pro-inflammatory cytokines (IL-8, TNFά). SEBC patients with elevated levels of both pro- and anti-inflammatory cytokines before treatment are the highest risk group of tumor progression and metastasis. Inhibition of the IL-8 effects or related CXC chemokines, TNFά, and others may have important consequences for the systemic treatment of SEBC.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yingni Wang ◽  
Siyu Tao ◽  
Zeyun Yu ◽  
Yun Luo ◽  
Yuan Li ◽  
...  

Background. Rheumatoid arthritis (RA) is a systemic immunodeficiency disease characterized by persistent synovial inflammation, pannus formation, and bone and cartilage destruction, resulting in joint malformations and function decline. Objective. The purpose of this study is to evaluate the effect of moxibustion on clinical symptoms and levels of pain-related indicators beta-endorphin (β-EP) and dynorphin (Dyn) in patients with RA and to explore the potential anti-inflammatory and analgesic mechanisms of moxibustion in RA treatment. Methods. A total of 64 patients with RA who met the inclusion criteria were randomly and equally classified into the control and treatment groups. The control group received conventional treatment (oral methotrexate, folate, or leflunomide prescribed for a long time). The treatment group was treated with moxibustion at ST36 (Zusanli), BL23 (Shenshu), and Ashi points with respect to the control group. Patients’ clinical symptoms and routine inspection indexes (rheumatoid factor [RF], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]) were recorded before and after treatment. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), β-EP, and Dyn were determined by enzyme-linked immunosorbent assay (ELISA). The software SPSS24.0 was used for statistical analysis. Results. (1) Compared with the pretreatment result, both of the two groups’ clinical symptoms and routine inspection indexes (RF, ESR, and CRP) improved ( P  < 0.05), and the improvement of clinical symptoms in the treatment group outperformed that in the control group ( P  < 0.05). (2) TNF-α and IL-1β levels decreased significantly in the treatment group after treatment ( P  < 0.01), while no significant difference was observed in the control group ( P  > 0.05). (3) β-EP and Dyn levels in the treatment group were significantly increased after treatment ( P  < 0.01, P  < 0.01), but the control group showed no significant difference ( P  > 0.05, P  > 0.05). It is worth mentioning that the serum TNF-α, IL-1β, β-EP, and Dyn levels between the two groups were significantly different after 8 weeks of treatment ( P  < 0.05). (4) Differences in the serum β-EP and Dyn levels in the patients of the treatment group were correlated with TNF-α and IL-1β levels after treatment, and the correlation was mainly negative (r < 0). Conclusion. Moxibustion can improve joint pain in patients with RA using conventional western medicine. One of the mechanisms may affect the serum β-EP and Dyn levels by downregulating the inflammatory factors to play an anti-inflammatory and analgesic role.


2015 ◽  
Vol 35 (6) ◽  
pp. 685-692 ◽  
Author(s):  
B Prabhu ◽  
D Balakrishnan ◽  
S Sundaresan

Introduction: Chemoprevention may involve perturbation of a variety of steps in tumor initiation, promotion, and progression. Objective: To investigate the antiproliferative and anti-inflammatory potential effects of diindolylmethane (DIM) and lupeol on experimental bladder carcinogenesis. Methods: Sixty healthy male Wistar rats were selected and randomly divided into six groups, with 10 rats in each group. Group I: control; group II: N-butyl- N-(4-hydroxybutyl) nitrosamine (BBN; 150 mg/gavage/twice a week) for 8 weeks, and then they were given 100 ppm concentrations of dimethylarsenic acid (DMA) in the drinking water for 28 weeks; group III: BBN + DMA + DIM (5 mg/kg body weight (b.w.)/day) treatment was started after BBN treatment, and it was orally administered for 28 weeks); group IV: BBN + DMA + lupeol (50 mg/kg b.w./day) treatment was started after BBN treatment, and it was orally administered for 28 weeks); and groups V and VI: DIM and lupeol treatment alone for 36 weeks. Bladder tissues were collected after 36th week study protocol for further analysis. Results: Our results revealed that DIM and lupeol treatment showed inhibition of tumor growth in the bladder by histopathological confirmations as well as significantly ( p < 0.001) increased the expression of phosphotensin (PTEN) and significantly ( p < 0.001) decreased the expression of tumor necrosis factor α, nuclear factor κβ (p65) were quantified using Western blot analysis. DIM and lupeol treatment significantly ( p < 0.001) decreased the levels of Cox-2 in bladder tissue samples and NMP 22 in urine samples were quantified using enzyme-linked immunosorbent assay method. Conclusion: Preventive DIM and lupeol administration act as potent Cox-2 inhibitors, which activates the tumor suppressor protein PTEN against experimental bladder carcinogenesis by antiproliferative and anti-inflammatory properties.


2019 ◽  
Vol 22 (4) ◽  
pp. 232-237 ◽  
Author(s):  
Jihong An

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH). Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry. Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels. Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shengchao Zhang ◽  
Jiankai Fang ◽  
Zhanhong Liu ◽  
Pengbo Hou ◽  
Lijuan Cao ◽  
...  

Abstract Background Muscle stem cells (MuSCs) are absolutely required for the formation, repair, and regeneration of skeletal muscle tissue. Increasing evidence demonstrated that tissue stem cells, especially mesenchymal stem cells (MSCs), can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory properties. Human mesenchymal stem cells (hMSCs) treated with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were reported to possess anti-inflammatory functions by producing TNF-stimulated gene 6 (TSG-6). However, whether human muscle stem cells (hMuSCs) also possess TSG-6 mediated anti-inflammatory functions has not been explored. Methods The ulcerative colitis mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. hMuSCs were pretreated with IFN-γ and TNF-α for 48 h and were then transplanted intravenously at day 2 of DSS administration. Body weights were monitored daily. Indoleamine 2,3-dioxygenase (IDO) and TSG-6 in hMuSCs were knocked down with short hairpin RNA (shRNA) and small interfering RNA (siRNA), respectively. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR and Western blot analysis were performed to evaluate gene expression. Results hMuSCs treated with inflammatory factors significantly ameliorated inflammatory bowel disease (IBD) symptoms. IDO and TSG-6 were greatly upregulated and required for the beneficial effects of hMuSCs on IBD. Mechanistically, the tryptophan metabolites, kynurenine (KYN) or kynurenic acid (KYNA) produced by IDO, augmented the expression of TSG-6 through activating their common receptor aryl hydrocarbon receptor (AHR). Conclusion Inflammatory cytokines-treated hMuSCs can alleviate DSS-induced colitis through IDO-mediated TSG-6 production.


Author(s):  
Maciej Kwiatek ◽  
Tomasz Gęca ◽  
Anna Kwaśniewska

The advantage in response of Th2 over Th1 is observed in normal pregnancy in peripheral blood. A disturbance of this balance can lead to symptoms of miscarriage and pregnancy loss. The aim of this study was to evaluate the pro- and anti-inflammatory cytokines in sera of women who were diagnosed with missed miscarriage in the first trimester and to compare this systemic immune response to the response in women with normal pregnancy. The study group consisted of 61 patients diagnosed with missed miscarriage. In total, 19 healthy women with uncomplicated first trimester created the control group. Cytokines were determined in the maternal serum by ELISA. The analysis included INF-γ, TNF-α, Il-1β, Il-4, Il-5, Il-6, Il-9, Il-10, Il-13 and TGF-β1. Th1 cytokine levels in the study group reached slightly higher values for INF-γ, Il-1β and slightly lower for IL-6 and TNF-α. In turn, Th2 cytokine levels in the study group were slightly higher (Il-9, Il-13), significantly higher (Il4, p = 0.015; Il-5, p = 0.0003) or showed no differences with the control group (Il-10). Slightly lower concentration involved only TGF-β1. Analysis of the correlation between levels of pro- and anti-inflammatory cytokines resulted in some discrepancies, without showing predominance of a specific immune response. The results did not confirm that women with missed miscarriage had an advantage in any type of immune response in comparison to women with normal pregnancy.


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