Higher PGD2 production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via miR-199a-3p/prostaglandin synthetase 2 axis

AbstractWe previously reported that synovial mast cells (MCs) from patients with rheumatoid arthritis (RA) produced TNF-α in response to immune complexes via FcγRI and FcγRIIA. However, the specific functions of synovial MCs in RA remain unclear. This study aimed to elucidate those functions. Synovial tissues and fluid were obtained from RA and osteoarthritis (OA) patients undergoing joint replacement surgery. Synovium-derived, cultured MCs were generated by culturing dispersed synovial cells with stem cell factor. We performed microarray-based screening of mRNA and microRNA (miRNA), followed by quantitative RT-PCR-based verification. Synovial MCs from RA patients showed significantly higher prostaglandin systhetase (PTGS)1 and PTGS2 expression compared with OA patients’ MCs, and they produced significantly more prostaglandin D2 (PGD2) following aggregation of FcγRI. PGD2 induced IL-8 production by human group 2 innate lymphoid cells, suggesting that PGD2-producing MCs induce neutrophil recruitment into the synovium of RA patients. PTGS2 mRNA expression in RA patients’ MCs correlated inversely with miRNA-199a-3p expression, which down-regulated PTGS2. RA patients’ synovial fluid contained significantly more PGD2 compared with OA patients’ fluid. Synovial MCs might regulate inflammation in RA through hyper-production of PGD2 following FcRγ aggregation. Our findings indicate functional heterogeneity of human MCs among diseases.

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The Autophagy Level Is Increased in the Synovial Tissues of Patients with Active Rheumatoid Arthritis and Is Correlated with Disease Severity

Mediators of Inflammation ◽

10.1155/2017/7623145 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 22

Author(s):

Li Zhu ◽

Huaizhou Wang ◽

Yu Wu ◽

Zhengwen He ◽

Yanghua Qin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Tissue ◽

Active Rheumatoid Arthritis ◽

Synovial Fibroblasts ◽

Serum Levels ◽

Serum Markers ◽

Effector Cells ◽

Joint Replacement Surgery ◽

Replacement Surgery ◽

Synovial Tissues

Rheumatoid arthritis (RA) is a complex and not fully understood autoimmune disease associated with multijoint damage. The main effector cells, the synovial fibroblasts, are apoptosis resistant and hyperplastic which indicate that autophagy level is high in synovial tissue. Real-time PCR, immunocytochemistry, and western blotting were used in this paper to study the autophagy status of the synovial tissues obtained from RA and OA patients at the time of joint replacement surgery. We further evaluated the correlation between autophagy levels with RA activity-associated serum markers with SPSS. The results showed that the expression levels (both in mRNA and in protein level) of autophagy-related proteins (belcin1, Atg5, and LC3) in the synovial tissue of patients with active rheumatoid arthritis (n=20) were significantly higher than those in OA patients (n=16). We further showed that the LC3-II/β-actin relative gray value was strongly correlated with the serum levels of several RA activity-related markers: CRP, ESR, CCP, and RF. Our results indicate that evaluating the autophagy level of synovial biopsies might be a useful way to diagnose RA and to estimate the disease activity. Reducing the expression level of autophagy-related genes might become a new therapeutic target for active rheumatoid arthritis.

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The Function and Molecular Mechanism of MicroRNA-429 in Rheumatoid Arthritis

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2352 ◽

2020 ◽

Vol 10 (7) ◽

pp. 945-950

Author(s):

Pengdong Zhang ◽

Bailong Yu ◽

Bin Lei ◽

Changlin Li ◽

Xiaoqiang Yuan

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Molecular Mechanism ◽

Synovial Tissue ◽

Luciferase Assay ◽

Rt Pcr ◽

Tnf Α ◽

Tlr4 Gene ◽

Synovial Tissues ◽

D Model

Objective: To explain the function and molecular mechanism of miRNA-429 in Rheumatoid Arthritis development. Methods: Collecting synovial tissue of 36 RA patients and 36 traumatic amputation patients, the miRNA-429 and TLR4 gene expressions were measured by RT-PCR. The SD rats were divided into NC, 14 d Model and 28 d Model groups. The IL-1β and TNF-α concentrations of serum were measured by Elisa assay in difference rats groups; The synovial tissue pathology was evaluated by HE staining; the miRNA-429 gene expression of rats groups were measured by RT-PCR, the TLR4 and NF-κB proteins expressions of rats groups were evaluated by IHC staining; the correlation between miRNA-429 and TLR4 were evaluated by Double luciferase assay. Results: Compared with normal synovial tissues, the miRNA-429 and TLR4 gene expression of synovial tissues were significantly difference in RA patients. In rats vivo study, we found that IL-1 and TNF-α concentrations were significantly up-regulation with time increasing (P < 0 05, respectively); inflammation degree was serious by HE staining and miRNA-429 gene expression was significantly reduced (P < 0.05, respectively); TLR4 and NF-κB proteins expressions were significantly up-regulation (P < 0.05, respectively) with time increasing; TLR4 was the target gene of miRNA-429 by Double luciferase assay. Conclusion: miRNA-429 over-expression stimulated RA development.

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Psoralea corylifolia L. Ameliorates Collagen-Induced Arthritis by Reducing Proinflammatory Cytokines and Upregulating Myeloid-Derived Suppressor Cells

Life ◽

10.3390/life11060587 ◽

2021 ◽

Vol 11 (6) ◽

pp. 587

Author(s):

Fu-Tzu Pai ◽

Cheng-You Lu ◽

Chia-Hsin Lin ◽

John Wang ◽

Ming-Cheng Huang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Suppressor Cells ◽

Clinical Severity ◽

Histopathological Analysis ◽

Human Rheumatoid Arthritis ◽

Psoralea Corylifolia ◽

Collagen Induced Arthritis ◽

Tnf Α ◽

Synovial Tissues ◽

Orthopedic Diseases

Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies of its effects on rheumatoid arthritis. The purpose of the study was to investigate the effects and mechanisms of concentrated herbal granules of PCL on rheumatoid arthritis to provide some insights for future development of new drug for the treatment of rheumatoid arthritis. Methods: We used collagen-induced arthritis (CIA) DBA/1J mice as an experimental model to mimic human rheumatoid arthritis. The mice were immunized with collagen on days 0 and 21 and then orally administered 200 mg/kg/day PCL on days 22–49. Starch was used as a control. The mice were sacrificed on day 50. Clinical phenotypes, joint histopathology, and immunological profiles were measured. Results: Compared to the CIA or CIA + Starch group, the CIA + PCL group had significantly ameliorated clinical severity and decreased paw swelling. Histopathological analysis of the hind paws showed that PCL mitigated the erosion of cartilage and the proliferation of synovial tissues. There were significant differences in the levels of TNF-α, IL-6 and IL-17A, as measured by ELISA, and the percentages of CD4 + IL-17A+, CD4 + TNF-α+, CD4 + IFN-γ+ T cells. Furthermore, we also found that in mice treated with CIA + PCL, the percentage and number of bone marrow-derived suppressor cells (MDSCs; Gr1+ CD11b+) increased significantly. Conclusions: We provided evidence for the potential antiarthritic effects of PCL through the inhibition of inflammation and increase of MDSCs. These findings indicate that PCL may be a promising therapeutic herb for the treatment of rheumatoid arthritis.

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Comparative Study for Carrot Juice and Selenium Supplement in Many Physiological and Biochemical Parameters in Patients with Rheumatoid Arthritis in Kirkuk City

Bionatura ◽

10.21931/rb/2021.06.04.15 ◽

2021 ◽

Vol 6 (4) ◽

pp. 2228-2232

Author(s):

Wedad Mahmood Lahmood Al-obaidi ◽

Mohanad Hasan Mahmood Al-Izzi ◽

Aya Saad yaseen

Keyword(s):

Rheumatoid Arthritis ◽

Rheumatoid Arthritis Group ◽

Carrot Juice ◽

Blood Samples ◽

Reactive Protein ◽

Tnf Α ◽

Group 3 ◽

Group 2 ◽

Physiological And Biochemical ◽

Β Carotene

Carrot juice is a critical source of vitamins, selenium, and β-carotene, which is suggested to protect from Rheumatoid Arthritis (RA). The present study aimed to show the effect of carrot juice supplementation compared to selenium tablet supplementation, so our study includes (44) blood samples belonging to young men with RA. All patients aged (20-45) years, 44 blood samples were obtained before treatment at week (0), twenty-four men with RA were supplied with fresh carrot juice. The other group of 20 patients was given an artificial selenium supplement for 21 days as well, and the results were analyzed.The samples were collected from Kirkuk hospital, and external specialized clinical from October/2019 to September /2020; experimental groups were divided into three groups: Group 1 : (44) men Rheumatoid arthritis (RA) before treatment, Group 2: (24) men with RA+ Carrot juice, Group 3: (20) men with RA +Selenium Tab, We reach to following results: the patients who have RA consumption Carrot juice and patients take up Se tab. show significant decrease respectively in RBCs, WBCs, ERS, and RF compared with the Rheumatoid arthritis group, so as the results show a significant decrease in Leptin, IL-6, C-Reactive Protein, and TNF-α concentrations in comparison with the Rheumatoid arthritis group. In contrast, we found a significant increase in GSH, Selenium concentrations, and VD3 in men with RA administration carrot juice and patients' consumption Se tab. Respectively compared with the RA group and, finally, our finding shows no difference in Ceruloplasmin in experimental groups.

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435 Human group 2 innate lymphoid cells differentiate into interleukin-17A producing cells in psoriasis

Journal of Investigative Dermatology ◽

10.1016/j.jid.2019.07.437 ◽

2019 ◽

Vol 139 (9) ◽

pp. S289

Author(s):

M.B. Teunissen ◽

J.H. Bernink ◽

Y. Ohne ◽

L. Krabbendam ◽

M.A. de Rie ◽

...

Keyword(s):

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Human Group ◽

Interleukin 17A ◽

Group 2

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Butyrate and propionate regulated proliferation and activation of human group–2 innate lymphoid cells (ILC2s)

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2018.12.902 ◽

2019 ◽

Vol 143 (2) ◽

pp. AB295

Author(s):

Keisuke Orimo ◽

Masato Tamari ◽

Hirohisa Saito ◽

Kenji Matsumoto ◽

Hideaki Morita

Keyword(s):

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Human Group ◽

Group 2

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The Role of Histamine in the Pathophysiology of Asthma and the Clinical Efficacy of Antihistamines in Asthma Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms20071733 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1733 ◽

Cited By ~ 14

Author(s):

Kohei Yamauchi ◽

Masahito Ogasawara

Keyword(s):

Mast Cells ◽

Allergic Asthma ◽

Clinical Efficacy ◽

Critical Role ◽

Allergic Airway Inflammation ◽

Specific Ige ◽

Smooth Muscle Contraction ◽

Lymphoid Cells ◽

Group 2 ◽

Perennial Allergens

Mast cells play a critical role in the pathogenesis of allergic asthma. Histamine is a central mediator released from mast cells through allergic reactions. Histamine plays a role in airway obstruction via smooth muscle contraction, bronchial secretion, and airway mucosal edema. However, previous clinical trials of H1 receptor antagonists (H1RAs) as a treatment for asthma were not successful. In recent years, type 2 innate immunity has been demonstrated to be involved in allergic airway inflammation. Allergic asthma is defined by IgE antibody-mediated mast cell degranulation, while group 2 innate lymphoid cells (ILC2) induce eosinophilic inflammation in nonallergic asthma without allergen-specific IgE. Anti-IgE therapy has demonstrated prominent efficacy in the treatment of severe allergic asthmatics sensitized with specific perennial allergens. Furthermore, recent trials of specific cytokine antagonists indicated that these antagonists were effective in only some subtypes of asthma. Accordingly, H1RAs may show significant clinical efficacy for some subtypes of allergic asthma in which histamine is deeply associated with the pathophysiology.

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