scholarly journals Baihu Jia Guizhi Decoction Improves Rheumatoid Arthritis Inflammation by Regulating Succinate/SUCNR1 Metabolic Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Huan Chen ◽  
Ting Pan ◽  
Panwang Liu ◽  
Ping Wang ◽  
Shijun Xu
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cell ◽  
Underlying Mechanism ◽  
Synovial Hyperplasia ◽  
Guizhi Decoction ◽  
Metabolic Signal ◽  
Anemarrhena Asphodeloides ◽  
Stimulation Of ◽  
Inflammatory Effect

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis. Succinate is an inflammatory metabolic signal that exacerbates RA synovitis by activating succinate receptor 1 (SUCNR1) to amplify the release of IL-1β. Thus, inhibition of succinate activation of SUCRN1 could be an effective method to inhibit the inflammation of RA. Baihu Jia Guizhi decoction (BHGZ), which is composed of Gypsum Fibrosum, Anemarrhena asphodeloides Bge., Cinnamomum cassia Presl., Glycyrrhiza uralensis Fisch., and Oryza sativa L., is a Traditional Chinese Medicine (TCM) prescription used to treat RA in clinic. In addition, TCM believes that damp and heat environment is one of the causes of RA. In this study, we tested the role of damp and heat environments in exacerbating RA inflammation and the anti-inflammatory effect of BHGZ, based on succinate/SUCNR1/IL-1β pathway in the adjuvant arthritis (AA) model with damp and heat environment (AA + DHE). Results showed that paw swelling and synovial pathology were significantly increased in AA rats, and these results were aggravated by stimulation in damp and heat environment. BHGZ improved AA + DHE rats’ paw swelling, synovial hyperplasia, and inflammatory cell infiltration and reduced IL-1β. In addition, AA rats significantly increased the expression of SUCNR1, and the stimulation of damp and heat environment not only increased the expression of SUCNR1 but also promoted the accumulation of succinate. BHGZ simultaneously reduced the concentration of succinate and the expression of SUCNR1. Finally, SDH activity was decreased in AA rats and AA + DHE rats, while BHGZ increased SDH activity and then reduced succinate concentration. Therefore, we prove that damp and heat environment deteriorated the inflammation of RA which is the activation of succinate/SUCNR1 pathway, while BHGZ regulates SDH activity to reduce the accumulation of succinate and inhibit the activation of SUCNR1 that is the underlying mechanism of its treatment of RA.

scholarly journals The Role of Simvastatin in the Therapeutic Approach of Rheumatoid Arthritis

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Lucia Cojocaru ◽  
Andrei Constantin Rusali ◽  
Cristina Şuţa ◽  
Anca Mihaela Rădulescu ◽  
Maria Şuţa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Active Rheumatoid Arthritis ◽  
Therapeutic Potential ◽  
Efficacy And Safety ◽  
Good Safety Profile ◽  
Study Support ◽  
Anti Inflammatory ◽  
Inflammatory Effect

The pleiotropic effects of statins, especially the anti-inflammatory and immunomodulatory ones, indicate that their therapeutic potential might extend beyond cholesterol lowering and cardiovascular disease to other inflammatory disorders such as rheumatoid arthritis. Therefore, we undertook a prospective cohort study to evaluate the efficacy and safety of simvastatin used for inflammation control in patients with rheumatoid arthritis. One hundred patients with active rheumatoid arthritis divided into two equal groups (the study one who received 20 mg/day of simvastatin in addition to prior DMARDs and the control one) were followed up over six months during three study visits. The results of the study support the fact that simvastatin at a dose of 20 mg/day has a low anti-inflammatory effect in patients with rheumatoid arthritis with a good safety profile.

scholarly journals Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Catarina Raposo ◽  
Ana Karolina de Santana Nunes ◽  
Rayana Leal de Almeida Luna ◽  
Shyrlene Meiry da Rocha Araújo ◽  
Maria Alice da Cruz-Höfling ◽  
...  
Keyword(s):  
Neuroprotective Effect ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
Wild Type ◽  
Glutathione S Transferase ◽  
Cox 2 ◽  
Inflammatory Regulation ◽  
Inos Inhibition ◽  
Inflammatory Effect

We recently demonstrated that sildenafil reduces the expression of cytokines, COX-2, and GFAP in a demyelinating model induced in wild-type (WT) mice. Herein, the understandings of the neuroprotective effect of sildenafil and the mediation of iNOS/NO system on inflammatory demyelination induced by cuprizone were investigated. The cerebella of iNOS−/−mice were examined after four weeks of treatment with cuprizone alone or combined with sildenafil. Cuprizone increased GFAP, Iba-1, TNF-α, COX-2, IL-1β, and IFN-γexpression, decreased expression of glutathione S-transferase pi (GSTpi), and damaged myelin in iNOS−/−mice. Sildenafil reduced Iba-1, IFN-γ, and IL-1βlevels but had no effect on the expression of GFAP, TNF-α, and COX-2 compared to the cuprizone group. Sildenafil elevated GSTpi levels and improved the myelin structure/ultrastructure. iNOS−/−mice suffered from severe inflammation following treatment with cuprizone, while WT mice had milder inflammation, as found in the previous study. It is possible that inflammatory regulation through iNOS-feedback is absent in iNOS−/−mice, making them more susceptible to inflammation. Sildenafil has at least a partial anti-inflammatory effect through iNOS inhibition, as its effect on iNOS−/−mice was limited. Further studies are required to explain the underlying mechanism of the sildenafil effects.

scholarly journals Pathogenesis and Function of Interleukin-35 in Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Pan Lin Xin ◽  
Li Fan Jie ◽  
Qian Cheng ◽  
Du Yi Bin ◽  
Cheng Wen Dan
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cell ◽  
T Regulatory Cells ◽  
Therapeutic Potential ◽  
Bone Destruction ◽  
Pathological Process ◽  
Interleukin 12 ◽  
Synovial Hyperplasia ◽  
And Function ◽  
Anti Inflammatory Cytokine

It is well known that RA (Rheumatoid arthritis) is an autoimmune disease characterized by multiple and symmetric arthropathy. The main pathological features of RA are synovial hyperplasia, angiogenesis, pannus formation, inflammatory cell infiltration, articular cartilage, bone destruction, and ultimately joint dysfunction, even deformity. IL-35 (Interleukin-35) is a new member of the IL-12 (Interleukin-12) family, which is an immunosuppressive and anti-inflammatory cytokine secreted mainly by Treg (T regulatory cells). There is evidence suggested that IL-35 can attenuate the progression of RA through influencing the immune and pathological process. It suggests that IL-35 played an important role in the pathogenesis of RA, and can be used as a potential target for the future treatment of RA. This review summarizes the recent advances of IL-35 in the pathological roles and the therapeutic potential roles in RA.

scholarly journals Regulation of osteoclastogenesis by mast cell in rheumatoid arthritis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Kyoung-Woon Kim ◽  
Bo-Mi Kim ◽  
Ji-Yeon Won ◽  
Hong-Ki Min ◽  
Kyung-Ann Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mast Cells ◽  
Osteoclast Differentiation ◽  
Serum Tryptase ◽  
Multinucleated Cells ◽  
Tnf Α ◽  
Concentration Levels ◽  
Gene Expression Levels ◽  
Stimulation Of

Abstract Background In the pathogenesis of rheumatoid arthritis (RA), the role of mast cells has not been revealed clearly. We aimed to define the inflammatory and tissue-destructive roles of mast cells in rheumatoid arthritis (RA). Methods Serum and synovial fluid (SF) concentration levels of tryptase, chymase, and histamine were quantified using ELISA. After activating mast cells using IL-33, the production of TNF-α, IL-1β, IL-6, IL-17, RANKL, and MMPs was determined using real-time PCR and ELISA. Osteoclastogenesis was assessed in CD14+ monocytes from peripheral blood and SF, which were cultured with IL-33-activated mast cells, by counting TRAP-positive multinucleated cells. Results The concentration levels of serum tryptase, chymase, and histamine and SF histamine were higher in patients with RA than in controls. FcεR1 and c-kit-positive mast cells were higher in RA synovium than in osteoarthritic (OA) synovium. Stimulation of mast cells by IL-33 increased the number of trypatse+chymase− and tryptase+chymase+ mast cells. IL-33 stimulation also increased the gene expression levels of TNF-α, IL-1β, IL-6, IL-17, RANKL, and MMP-9 in mast cells. Furthermore, IL-33 stimulated human CD14+ monocytes to differentiate into TRAP+ multinucleated osteoclasts. When CD14+ monocytes were co-cultured with mast cells, osteoclast differentiation was increased. Additionally, IL-33-activated mast cells stimulated osteoclast differentiation. The inhibition of intercellular contact between mast cells and monocytes using inserts reduced osteoclast differentiation. Conclusions IL-33 increased inflammatory and tissue-destructive cytokines by activation of mast cells. Mast cells stimulated osteoclast differentiation in monocytes. Mast cells could stimulate osteoclastogenesis indirectly through production of tissue-destructive cytokines and directly through stimulation of osteoclast precursors.

scholarly journals The role of calprotectin in rheumatoid arthritis

2019 ◽  
Vol 7 (4) ◽  
pp. 126-131 ◽  
Author(s):  
Qin Wang ◽  
Weiqian Chen ◽  
Jin Lin
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cell ◽  
Radiographic Progression ◽  
Inflammatory Factors ◽  
Acute Phase Reactants ◽  
Heterodimeric Complex ◽  
Inflammatory Autoimmune Disease ◽  
Fluid Levels ◽  
Clinical Disease Progression

Abstract Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by inflammatory cell infiltration, high levels of cytokines, and erosion of cartilage and bone in joints. Calprotectin (CLP), as a recently described member of S100 family proteins, is a heterodimeric complex of S100A8 and S100A9. Currently, plenty of studies have indicated significantly increased serum and synovial fluid levels of CLP in patients with RA. It was reported that CLP was related to cell differentiation, migration, apoptosis, and production of pro-inflammatory factors in RA. In addition, there are the positive relationships between serum, synovial CLP and traditional acute phase reactants, disease activity, ultrasound and radiographic progression of joints, and treatment response of RA. In this review, we mainly discuss the role of CLP in the pathogenesis of RA as well as its potential to estimate clinical disease progression of RA patients.

Perspective and Potential of A2A and A3 Adenosine Receptors as Therapeutic Targets for the Treatment of Rheumatoid Arthritis

2019 ◽  
Vol 25 (26) ◽  
pp. 2859-2874 ◽  
Author(s):  
Yogendra Pal ◽  
Nabamita Bandyopadhyay ◽  
Rashmi S. Pal ◽  
Sarfaraz Ahmed ◽  
Shantanu Bandopadhyay
Keyword(s):  
Rheumatoid Arthritis ◽  
Adenosine Receptors ◽  
Vital Role ◽  
Receptor Subtypes ◽  
Immune Disorder ◽  
Inflammatory Conditions ◽  
Tnf Α ◽  
Near Future ◽  
Inflammatory Effect

Adenosine is a purine nucleoside which is an effective controller of inflammation. The inflammatory effect of adenosine is expressed via its four receptor subtypes viz. A1, A2A, A2B and A3. The various inflammatory conditions including rheumatoid arthritis (RA) are initiated by adenosine receptors of which A2A and A3 play a vital role. RA primarily is an auto-immune disorder which is manifested as chronic inflammation in the synovial lining of joints. In order to develop an effective treatment, the role of cytokines, IL–1, TNF-α and IL–6 is crucial. Besides, the knowledge of PI3K-PKB/Akt and NF-kB signaling pathway is also important to understand the antiinflammatory targets. Methotrexate along with various other molecules like, NSAIDs and DMARDs are presently used as treatment lines for controlling RA. The enhanced knowledge of the preclinical stages and pathogenesis along with recent potent therapeutics raises the hopes that RA can be prevented in the near future.

scholarly journals Interluekin-35 in Asthma and Its Potential as an Effective Therapeutic Agent

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Peng Gao ◽  
Zhenzhong Su ◽  
Xuejiao Lv ◽  
Jie Zhang
Keyword(s):  
Rheumatoid Arthritis ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Inflammatory Cell ◽  
Allergic Inflammation ◽  
Negative Regulator ◽  
Current Evidence ◽  
Epstein Barr

Interleukin- (IL-) 35 is a member of the IL-12 cytokine family and a heterodimeric protein formed by Epstein-Barr-induced gene 3 (EBI3) and IL-12p35. Emerging evidence shows that IL-35 is a key player in the regulation of cellular communication, differentiation, and inflammation. Altered IL-35 expression has been found in disease conditions such as cancer, rheumatoid arthritis, and, more recently, asthma. In cancer, IL-35 is involved in the regulation of tumorigenesis, cancer progression, and metastasis. In rheumatoid arthritis, IL-35 acts as a negative regulator of inflammation. Similarly, IL-35 also appears to suppress allergic inflammation in asthma. In an in vivo murine model of asthma, transfer of adenovirus-mediated IL-35 markedly reduced the degree of airway hyperresponsiveness (AHR) and inflammatory cell infiltration. Many studies have shown the involvement of IL-35 in a number of aspects of allergic inflammation, such as eosinophil and neutrophil recruitment as well as inhibition of inflammatory mediators of the Th2 subtype. However, the exact molecular mechanisms underlying the role of IL-35 in human asthma have yet to be fully elucidated. This review describes the current evidence regarding the role of IL-35 in the pathophysiology of asthma and evaluates the potential of IL-35 as a biomarker for airway inflammation and a therapeutic target for the treatment of asthma.

scholarly journals Cytokines of the Th1 and Th2 type in sera of rheumatoid arthritis patients; correlations with anti-Hsp40 immune response and diagnostic markers.

2010 ◽  
Vol 57 (3) ◽  
Author(s):  
Stefan Tukaj ◽  
Agnieszka Kotlarz ◽  
Agnieszka Jóźwik ◽  
Zaneta Smoleńska ◽  
Ewa Bryl ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Healthy Controls ◽  
Flow Cytometric ◽  
Das 28 ◽  
Systemic Inflammatory Disease ◽  
Cytokine Levels ◽  
Shock Proteins ◽  
Cytometric Bead Array Assay ◽  
Inflammatory Effect

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease which affects approximately 1% of the population worldwide. Recent research on the role of heat shock proteins (Hsps) in RA development indicates that they may have pro- or anti-inflammatory effect, most probably via modulating cytokine secretion. We investigated type Th1 (INFγ, TNFα, IL-2) and type Th2 (IL-10, IL-6, IL-4) cytokine levels in sera of RA patients and healthy controls, using flow cytometric bead array assay, and searched for correlations between the cytokine levels and serum antibodies against bacterial (DnaJ) and human (Hdj1, Hdj2 and Hdj3) Hsp40 proteins, as well as clinical and laboratory parameters. The levels of all cytokines studied were significantly increased in RA patients; the highest increase relative to healthy controls (7-fold) was observed for IL-6 and its levels correlated positively with the antibodies directed to DnaJ and to the C-terminal domain of Hdj2, and with diagnostic parameters (DAS 28, Steinbrocker RTG criteria, ARA/7, ESR, TEN, SW and GH). INFγ levels correlated negatively with DAS 28, ESR, TEN and SW. No correlations were found for TNFα, IL-2 or IL-4. Our results support the hypothesis of Hsp40 involvement in RA as well as indicate that IL-6 serum level is a good marker of the RA activity.

scholarly journals Role of Inflammatory Cell Responses in Stimulating Fibroblasts in Diabetic Oral Ulcer after Treatment with Liquid Smoke of Coconut Endocarp: A Histological Assessment

2020 ◽  
Author(s):  
Diah Savitri Ernawati ◽  
Meircurius Dwi Condro Surboyo ◽  
Nurina Febriyanti Ayuningtyas ◽  
Ayu Anggraini Broto Nagoro
Keyword(s):  
Ulcer Healing ◽  
Inflammatory Cell ◽  
Oral Ulcer ◽  
Histological Assessment ◽  
Cell Responses ◽  
Liquid Smoke ◽  
Diabetic Model ◽  
Ulcer Model ◽  
Inflammatory Effect

Abstract Objective The liquid smoke of coconut endocarp (LS-CE) contains high antioxidants that promote oral ulcer healing in diabetics. This study reveals the profile of inflammatory cell responses to oral ulcer healing in diabetics under treatment with LS-CE. Materials and Methods A diabetic model was induced with alloxan. Treatment with LS-CE was performed on oral ulcer at a dose of 1 μL/g weight for 3, 5, and 7 days. The anti-inflammatory effect was tested on animal’s oral ulcer model by measuring the inflammatory cell responses of the neutrophils, macrophages, lymphocytes, and fibroblasts through histological assessment. Results The LS-CE stimulated the healing by simultaneously increasing the inflammatory cell responses. The numbers of neutrophils, macrophages, and fibroblasts after treatment for 7 days are higher than that after 3 days and 5 days (p < 0.01), but not for neutrophils. The LS-CE shows increase in the fibroblasts by hastening responses of macrophage recruitment by five times, but not neutrophil and lymphocyte recruitment. The higher phenolic compounds in LS-CE are responsible for increase in the proliferation of fibroblasts, as it hastens cellular responses of macrophages. Conclusions The application of LS-CE enables hastening of the healing of diabetic oral ulcer by stimulating the macrophages.

scholarly journals Activation of Extracellular Signal-Regulated Protein Kinases 1 and 2 (ERK1/2) by Free Fatty Acid Receptor 1 (FFAR1/GPR40) Protects from Palmitate-Induced Beta Cell Death, but Plays no Role in Insulin Secretion

2015 ◽  
Vol 35 (4) ◽  
pp. 1537-1545 ◽  
Author(s):  
Madhura Panse ◽  
Felicia Gerst ◽  
Gabriele Kaiser ◽  
Charlott-Amélie Teutsch ◽  
Rebecca Dölker ◽  
...  
Keyword(s):  
Cell Death ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Prolonged Exposure ◽  
Underlying Mechanism ◽  
Tunel Staining ◽  
Western Blots ◽  
Beta Cell Death ◽  
Stimulation Of

Aims: GPR40/FFAR1 mediates palmitate-induced stimulation of insulin secretion but its involvement in lipotoxicity is controversial. Our previous observations suggest that FFAR1/GPR40 agonists protect against lipotoxicity although the underlying mechanism remains elusive. The present study examines the role of ERK1/2 and GPR40/FFAR1 in palmitate-induced stimulation of insulin secretion and beta cell death. Methods: Insulin secretion of INS-1E cells was measured by radioimmunoassay. Protein phosphorylation was examined on Western blots. Apoptosis was assessed by TUNEL staining. Results: Palmitate and the GPR40/FFAR1 agonist TUG-469 increased phosphorylation of ERK1/2 at low (2.8 mmol/L) and high (12 mmol/L) glucose but stimulated insulin secretion only at high glucose. The MEK1 inhibitor PD98059 significantly reduced phosphorylation of ERK1/2 but did not reverse the stimulation of secretion induced by glucose, palmitate or TUG-469. PD98059 rather augmented glucose-induced secretion. Prolonged exposure to palmitate stimulated apoptosis, an effect counteracted by TUG-469. PD98059 accentuated palmitate-induced apoptosis and reversed TUG-469-mediated inhibition of cell death. Conclusions: Activation of ERK1/2 by palmitate and GPR40/FFAR1 agonist correlates neither with stimulation of insulin secretion nor with induction of apoptosis. The results suggest a significant anti-apoptotic role of ERK1/2 under conditions of lipotoxicity.

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