scholarly journals Protectin DX restores Treg/Th17 cell balance in rheumatoid arthritis by inhibiting NLRP3 inflammasome via miR-20a

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Shengwei Jin ◽  
Siyuan Sun ◽  
Hanzhi Ling ◽  
Jinglan Ma ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Receptor Protein ◽  
Mice Model ◽  
T Helper 17 ◽  
Joint Injury ◽  
Potential Biomarker ◽  
Protectin Dx ◽  
Cell Balance

AbstractRegulatory T-cell (Treg)/T-helper 17 (Th17) cell balance plays an important role in the progression of rheumatoid arthritis (RA). Our study explored the protective effect of protectin DX (PDX), which restored Treg/Th17 cell balance in RA, and the role of the nucleotide-binding domain (NOD)–like receptor protein 3 (NLRP3) inflammasome pathway in this process. Using mass spectrometry, we discovered that level of PDX decreased in active-RA patients and increased in inactive-RA patients compared with HCs, and serum PDX was a potential biomarker in RA activity detection (area under the curve [AUC] = 0.86). In addition, a collagen-induced arthritis (CIA) mice model was constructed and PDX obviously delayed RA progression in the CIA model, upregulating Tregs and anti-inflammatory cytokines while downregulating Th17 cells and pro-inflammatory cytokines. Moreover, NLRP3 knockout and rescue experiments demonstrated that NLRP3 participated in PDX-mediated Treg/Th17 cell balance restoration, joint injury amelioration and inflammatory-response attenuation using Nlrp3−/− mice. Furthermore, microarray and verified experiments confirmed that PDX reduced NLRP3 expression via miRNA-20a (miR-20a). In summary, we confirmed for the first time that PDX could effectively ameliorate CIA progression by restoring Treg/Th17 cell balance, which was mediated by inhibition of the NLRP3 inflammasome pathway via miR-20a.

DAPK1 may be a potential biomarker for arterial aneurysm in clinical treatment and activated inflammation levels in arterial aneurysm through NLRP3 inflammasome by Beclin1

2021 ◽  
pp. 096032712110416
Author(s):  
Senyan Wu ◽  
Wei Lu ◽  
Guobing Cheng ◽  
Jiawen Wu ◽  
Sheng Liao ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Nlrp3 Inflammasome ◽  
Clinical Treatment ◽  
Arterial Aneurysm ◽  
Mice Model ◽  
Human Artery ◽  
Potential Biomarker ◽  
Death Associated Protein Kinase ◽  
Vitro Model ◽  
Underlying Mechanisms

Background Death-associated protein kinase (DAPK1) is one of the positive regulators of apoptosis, and it is widely involved in apoptosis induced by multiple pathways. We examined that the function of DAPK1 in Clinical treatment of arterial aneurysm and its underlying mechanisms. Arterial aneurysm is a common cerebrovascular disease with high disability and fatality rate. Objectives Male C57BL/6 mice or DAPK1−/− mice were injected with 50 mg/kg pentobarbital sodium and then were injected with angiotensin II (AngII) infusion for vivo model. hASMCs (Human artery smooth muscle cell) were treated with murine recombinant IL-6 (20  ng ml−1; Cell Signaling) for vitro model. Results DAPK1 gene, mRNA expression, and protein expression were induced in mice of arterial aneurysm. DAPK1 mRNA expression was increased and Area Under Curve was 0.9075 in patients with arterial aneurysm. Knockout of DAPK1 decreased inflammation and vascular injury in mice model of arterial aneurysm. Beclin1/NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) signal pathway is a critical downstream effector of DAPK1 by TAP production. The regulation of Beclin1 participated in the effects of DAPK1 on inflammation of arterial aneurysm by ATP-dependent NLRP3 inflammasome. The regulation of NLRP3 participated in the effects of DAPK1 on inflammation of arterial aneurysm. Conclusion Collectively, our data indicated that DAPK1 may be a potential biomarker for arterial aneurysm in clinical treatment and activated inflammation levels in arterial aneurysm through NLRP3 inflammasome by Beclin1. DAPK1 might be a key pathogenic event underlying excess inflammation of arterial aneurysm.

scholarly journals Datura Metel L. Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis and Inhibits Inflammatory Cytokines Production through TLR7/8–MyD88–NF-κB–NLRP3 Inflammasome Pathway

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2157 ◽  
Author(s):  
Bing-You Yang ◽  
Yan-Gang Cheng ◽  
Yan Liu ◽  
Yuan Liu ◽  
Jin-Yan Tan ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Protective Effect ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Primary Response ◽  
Intercellular Adhesion Molecule ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mice Model ◽  
Intercellular Adhesion Molecule 1 ◽  
Datura Metel

Background: Psoriasis is a chronic, immune-mediated inflammatory skin disease, and the inflammatory response plays an important role in its development and progression. Datura metel L. is a traditional Chinese medicine that exhibited a significant therapeutic effect on psoriasis in our previous study due to its remarkable anti-inflammatory effect. Meanwhile, the mechanism underlying its effects on psoriasis is still unclear. Methods: An imiquimod-induced psoriasis-like dermatitis mouse model was constructed to evaluate the protective effect of the effective part of Datura metel L. (EPD), which was verified by evaluations of the Psoriasis Area and Severity Index (PASI) score. Hematoxylin and eosin (H&E) staining, immunohistochemical examination, enzyme-linked immunosorbent assay (ELISA), and Western blot were used to measure the inflammatory cytokines and the protein expression associated with the Toll-like receptor 7– myeloid differentiation primary response gene 88–nuclear Factor-κB–nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (TLR7/8–MyD88–NF-κB–NLRP3) inflammasome pathway. Results: EPD significantly decreased the PASI, reduced epidermal thickness, and decreased the proliferation and differentiation of epidermal cells in psoriasis-like dermatitis C57BL/6 mice induced by imiquimod (IMQ). Furthermore, EPD reduced the infiltration of CD3+ cells to psoriatic lesions, as well as ameliorated the elevations of intercellular adhesion molecule 1 (ICAM-1) and inhibited the production of imiquimod-induced inflammatory cytokines, including IL-1β, IL-2, IL-6, IL-10, IL-12, IL-17, IL-22, IL-23, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and interferon-γ (IFN-γ). Besides, EPD decreased the imiquimod-induced expression levels of TLR7, TLR8, TRAF6, MyD88, p-IKKα, p-IKBα, p-NF-κB, NLRP3, apoptosis-associated speck-like protein contained a caspase recruitment domain (ASC), cysteinyl aspartate specific proteinase 1 (caspase-1), and IL-1β. Conclusion: This study demonstrated that EPD exhibited a protective effect on an imiquimod-induced psoriasis mice model by inhibiting the inflammatory response, which might be ascribed to the inhibition of the TLR7/8–MyD88–NF-κb–NLRP3 inflammasome pathway.

Evaluating the efficacy of intra-articular injections of platelet rich plasma (PRP) in rheumatoid arthritis patients and its impact on inflammatory cytokines, disease activity and quality of life.

2020 ◽  
Vol 16 ◽  
Author(s):  
Dalia S. Saif ◽  
Nagwa N. Hegazy ◽  
Enas S. Zahran
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Platelet Rich Plasma ◽  
Joint Inflammation ◽  
Monthly Interval ◽  
Post Injection ◽  
Tnf Α

Background: Among rheumatoid arthritis patients (RA), general disease activity is well regulated by diseasemodifying anti-rheumatic medications (DMARDS), but sometimes local inflammation still persists among a few joints. Adjuvant modern molecular interventions as Platelet Rich Plasma (PRP) with a suggested down regulating effect on inflammatory mediators has a proven effect in management of RA. We aim to evaluate the therapeutic effect of intra-articular PRP versus steroid in RA patients and their impact on inflammatory cytokines IL1B , TNF α, local joint inflammation, disease activity and quality of life (QL). Methods: Open labeled parallel randomized control clinical trial was carried out on 60 RA patients randomly divided into 2 groups, Group 1: included 30 patients received 3 intra-articular injections of PRP at monthly interval, Group 2: included 30 patients received single intra-articular injection of steroid. They were subjected to clinical, laboratory, serum IL1B and TNF α assessment at baseline and at 3, 6 months post injection. Results: Patients of both groups showed improvements in their scores of evaluating tools at 3months post injection and this improvement was persistent in the PRP group up to 6 months post injection while it was continued only for 3 months in the steroid group. Conclusions: PRP is a safe, effective and useful therapy in treating RA patients who had insufficient response and persistent pain and inflammation in just one or two joints through its down regulating effect on inflammatory cytokines IL1B, TNF α with subsequent improvement of local joint inflammation, disease activity and QL.

scholarly journals Serum IL-35 is decreased in overweight patients with rheumatoid arthritis: its correlation with Th1/Th2/Th17-related cytokines

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuxuan Li ◽  
Yang Jie ◽  
Xiaofei Wang ◽  
Jing Lu
Keyword(s):  
Rheumatoid Arthritis ◽  
Medical Records ◽  
Clinical Information ◽  
Serum Cytokines ◽  
Healthy Donors ◽  
Potential Biomarker ◽  
Tnf Α ◽  
Ifn Γ ◽  
Quantitative Changes ◽  
Anti Inflammatory Cytokine

Abstract Background Obesity is correlated with worse drug responses and high disease activity in patients with rheumatoid arthritis (RA). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that mainly produced by regulatory T (Treg). This study was performed to analyze whether IL-35 was correlated with obesity in RA and investigate the correlation between other Th1/Th2/Th17-related cytokines and obesity in RA. Results The serum IL-35 level was analyzed in RA (n = 81) and healthy donors (n = 53) by ELISA assay, and was compared between three groups (body mass index (BMI) < 18.5,≥18.5 to 25, > 25). Serum cytokines including IL-2, IL-4, IL-10, IL-17, INF-γ, TNF-α levels were measured using Flowcytometry assay. Clinical information was extracted from medical records. Serum IL-35 level in overweight patients were significantly decreased than those in lean patients. Furthermore, Th1/Th2/Th17-related cytokines from overweight patients with RA showed the characteristic immunological features. Serum IL-6, IL-17 and TNF-α levels were positively correlated with BMI. However, serum IL-2, IL-4, IL-10 and IFN-γ concentrations were not correlated with BMI. Conclusions Quantitative changes in serum IL-35 level were characteristic in overweight patients with RA. These findings indicate that IL-35 plays an important role in the development of RA and may prove to be a potential biomarker of active RA.

scholarly journals The Role of Collagen Triple Helix Repeat-Containing 1 Protein (CTHRC1) in Rheumatoid Arthritis

2021 ◽  
Vol 22 (5) ◽  
pp. 2426
Author(s):  
Askhat Myngbay ◽  
Limara Manarbek ◽  
Steve Ludbrook ◽  
Jeannette Kunz
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Targets ◽  
Triple Helix ◽  
Cancer Metastasis ◽  
Bone Erosion ◽  
Cartilage Destruction ◽  
Patient Treatment ◽  
Collagen Triple Helix ◽  
Potential Biomarker

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and is associated with cancer metastasis to the bone and poor patient prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression. We will discuss emerging evidence linking CTHRC1 to the pathogenic behavior of fibroblast-like synoviocytes and to cartilage and bone erosion through modulation of the balance between bone resorption and repair.

scholarly journals POS0567 HEPCIDIN IS POTENTIAL BIOMARKER TO DISTINGUISH BETWEEN IRON DEFICIENCY ANEMIA AND ANEMIA OF INFLAMMATION IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 518.2-518
Author(s):  
E. Galushko ◽  
A. Semashko ◽  
A. Gordeev ◽  
A. Lila
Keyword(s):  
Rheumatoid Arthritis ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Complete Blood Count ◽  
Deficiency Anemia ◽  
Reactive Protein ◽  
Potential Biomarker ◽  
Serum Hepcidin ◽  
Proper Diagnosis ◽  
Anemia Of Inflammation

Background:Anemia of inflammation (AI) and iron deficiency anemia (IDA) are the two most prevalent forms of anemia in patients with rheumatoid arthritis (RA). Diagnosis becomes challenging if AI is associated with true ID (AI/ID), as there is still a lack of a gold standard for differentiation between AI and AI/ID. However, as therapies to overcome anemia differ, proper diagnosis and understanding of underlying pathophysiological regulations are necessary.Objectives:The aim of the study was to evaluate the clinical efficiency of hepcidin, a key regulator of iron metabolism, in the diagnosis of IDA, as well as the differential diagnosis of AI/ID and AI in patients with RA.Methods:The study was undertaken 96 patients with RA, 67 of them were diagnosed anemia according to WHO criteria (104,3±21,4 g/l). Anemic patients and anemia-free patients with RA (n=29) were comparable (p>0.05) in age (44.4±14.8 and 49.8±9.3 years), disease duration (73.5±65.4 and 59.8±48.3 months) and DAS28 (6.3±1.6 and 5.9±1.9). All cases were subjected to following tests: complete blood count with peripheral smear, serum C-reactive protein, serum interleukin-6, iron studies, serum soluble transferrin receptor (sTfR), and serum hepcidin. Patients with RA and anemia were divided two groups: 25 patients with IDA and 42 - with AI. The AI cases were subdivided into pure AI and AI with coexistent ID (n=15).Results:The mean serum hepcidin concentration was significantly increased in pure AI patients (123.85±25.8 ng/mL) as compared to those in IDA patients (63.9±22.8 ng/mL, P < 0.05) and anemia-free patients with RA (88.1±39.09 ng/mL). Also, compared to pure AI patients [normal sTfR levels (<3 µg/mL)], the serum hepcidin concentration was reduced significantly in AI patients with ID [high sTfR levels (≥3 µg/mL)] with a mean of 79.0±23.97 ng/mL.Conclusion:Hepcidin measurement can provide a useful tool for differentiating AI from IDA and also help to identify an iron deficiency in AI patients. This might aid in the appropriate selection of therapy for these patients.Disclosure of Interests:None declared

scholarly journals AB0827 SERUM NESPHATIN-1 IN PATHOGENESIS RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1437.2-1438
Author(s):  
T. Kvlividze ◽  
V. Polyakov ◽  
В. Zavodovsky ◽  
Y. Polyakova ◽  
L. Seewordova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Serum ◽  
Inflammatory Cytokines ◽  
Inflammatory Markers ◽  
Healthy People ◽  
Healthy Individuals ◽  
Markers Of Inflammation ◽  
High Level ◽  
Pro Inflammatory Cytokines

Background:Interest in highly specialized tissue cytokines contributed to the discovery of new biologically active molecules. Nesfatin-1 (NF) - discovered in 2006 as an anorexigenic factor. NF-1 is believed to be involved in the regulation of energy homeostasis by regulating appetite and water intake. The role of NF-1 in the pathogenesis of inflammatory diseases is poorly understood. Recently, studies have found a relationship between an increased level of NF-1 and inflammatory markers in various pathologies.Objectives:Study of the level of nesfatin-1 in the blood serum of healthy people, determination of the correlation between the level of NF-1 with the severity of clinical symptoms and classic markers of inflammation in patients with RA.Methods:120 persons were examined: 90 patients with RA and 30 healthy people. All patients underwent a complete clinical and laboratory examination. Plasma NF-1 levels were determined using commercial test systems (RaiBiotech, cat # EIA-NESF) according to the manufacturer’s instructions. Patients with various forms of RA were comparable in age to the group of healthy individuals. Statistical processing of clinical examination data was carried out using the “STATISTICA 10.0 for Windows” software package. Quantitative data were processed statistically using the parametric Student’s t-test, qualitative data using the non-parametric chi-square test. The significance of differences between groups was determined using analysis of variance. The results were considered statistically significant at p <0.05.Results:The average level of NF-1 in blood serum in healthy individuals was 31.79 ± 3.21 ng / ml (M ± σ). The level of normal NF-1 values in healthy individuals, defined as M ± 2σ, ranged from 25.3 to 37.83 ng / ml. There was no significant difference in the levels of circulating NF-1 and BMI in healthy individuals and patients with RA (p> 0.05). The inverse relationship of a lower level of NF-1 with an increase in BMI was not significant.Group 1 (66 patients with RA) with increased serum NF-1 levels (> 37.83 ng / ml), and group 2 (44 patients) with normal values (<37.83 ng / ml). A high level of NF-1 was characteristic for patients with high activity according to DAS28, RF seropositive, ACCP-positive, with extra-articular manifestations, who had been ill for 10 years or more. A reliable relationship between the level of NF-1 in the blood serum and laboratory parameters of RA activity - ESR, CRP, was shown, and secondary synovitis was more common. Our data show a direct correlation between the NF-1 level of the pro-inflammatory markers of RA.Conclusion:The positive correlation between the level of NF-1 and classical markers of inflammation, such as CRP and ESR, confirms the involvement of NF-1 in the pathophysiology of inflammation in RA. This is also evidenced by the correlation of a high level of NF-1 in the blood serum with a more severe clinical picture of RA. It is known that NF-1 can promote the release of pro-inflammatory cytokines such as interleukin-8 (IL-8), interleukin-6 (IL-6), and macrophage inflammatory protein-1a (MIP-1a) in the chondrocytes of RA patients.It is necessary to further study the role of NF-1 in the pathogenesis of systemic inflammatory reactions and the possibility of targeting pro-inflammatory cytokines, the possibility of regulating the level of NF-1 by drugs.References:[1]Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R. Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R., Polyakova Yu.V., Sivordova L.E., Yakovlev A.T., Zborovskaya I.A. Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Klinicheskaya Laboratornaya Diagnostika (Russian Clinical Laboratory Diagnostics). 2019; 64 (1): 53-56 (in Russ.).Disclosure of Interests:None declared

scholarly journals AB0167 PECULIARITIES OF INTERACTION OF CHRONIC INFLAMMATION AND DEPRESSION IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1110.1-1110
Author(s):  
A. Aleksandrov ◽  
N. Aleksandrova
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Inflammatory Cytokines ◽  
Depressive Disorders ◽  
Severe Depression ◽  
Mild Depression ◽  
Group Iii ◽  
Group I ◽  
Severity Of Depression ◽  
Pro Inflammatory Cytokines

Background:In patients with rheumatoid arthritis (RA), a high prevalence of depression and anxiety is observed, and the severity of these conditions depends on the degree of vitamin D deficiency. The role of the main mediator, with the help of which psychological and physical stress factors can contribute to the development of depression and systemic diseases, has been attributed to inflammation in recent years.Objectives:to assess the dependence of depressive disorders on vitamin D deficiency and the level of pro-inflammatory cytokines in patients with RA.Methods:88 women with a reliable diagnosis of RA (mean age 54.2 ± 12.0 years old, disease duration 9.0 [3.5; 16.0] years) were under observation. Beck’s depression inventory (BDI-II) was used to assess the presence of depressive symptoms. ELISA test was used to measure serum cytokines (IL-1, IL-6) and serum 25(OH)D levels.Results:The presence of depression was found in 66% of patients with RA. An insufficient level of 25(OH)D (<30 ng / ml) was determined in 89.8% of cases. In RA patients with no signs of depression, the level of 25(OH)D showed maximum values and significantly differed from that in the groups of patients with moderate (p = 0.028) and severe depression (p <0.001). A negative correlation (r = -0.38, n = 88, p <0.05) was established between the level of 25(OH)D and the severity of depression. A positive relationship was also found between 25(OH)D and ESR (r = 0.29, n = 73, p <0.05) and a negative relationship with the number of painful joints (r = -0.29, n = 76, p <0.05). Probably, vitamin D is indirectly involved in inflammatory processes in joints and in central sensitization, which provokes chronic pain and psychological disorders in patients with RA.The level of IL-6 in patients with RA with moderate and severe depression (n=18; 14.6 ± 6.7 pg/ml) significantly exceeded the parameters of patients with RA without depressive disorders (n=30; 9.8 ± 3.7; p = 0.003). There was also a tendency to increase IL-6 in the group of patients with moderate and severe depression compared with patients with mild depression (p = 0.06). IL-1β values significantly increased with the progression of depression (without depression – mild depression, p = 0.034; mild – moderate, p <0.001; moderate – severe depression, p = 0.044). A positive correlation of average severity was revealed between the degree of depression (according to BDI-II) and the dose of glucocorticoids (GC) at the time of the study (r = 0.33, p = 0.002). An increase in the GC dose in the short term can aggravate depressive disorders in RA patients (Table 1).Table 1.Indicators of levels of depression and IL-1β depending on the dose of GCGroup I (n=26), without GCGroup II (n=45),GC <10 mg / dayGroup III (n=17),GC ≥10 mg / dayDepression level according to BDI-II, points (Me [P25; P75])8,5[5;16]14[9;17]19[14;29] *III-IIL-1β level, pg / ml (M ± SD)4,57 ± 1,83*I-II6,04 ± 3,276,52 ± 5,16* - intergroup differences are reliable, p <0.05Patients who used GC in a daily dose of ≥10 mg / day (group III) had a higher degree of depression compared to patients with RA from group I (z = -2.98; p = 0.003). In patients with RA in the first group, the level of IL-1β was significantly higher (pI-II = 0.039) than in patients with GC prescription in minimal doses (up to 10 mg / day) (Table 1). Glucocorticoid hormones suppress pro-inflammatory cytokines. As a rule, this effect is not observed in patients with depression. This fact may indicate a violation of homeostatic mechanisms. IL-1β is thought to be the first step in the pro-inflammatory response to psychological stress and is capable of inducing a subsequent cascade of other inflammatory cytokine responses.Conclusion:Restoring the normal level of 25(OH)D in the blood serum of patients with RA can positively affect psychological indicators by reducing the severity of depression and manifestations of pain. The activation of pro-inflammatory cytokines during stress and depression suggests that suppression of the inflammatory response can also reduce the symptoms of depression in RA patients.Disclosure of Interests:None declared

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