scholarly journals 20S-Hydroxyvitamin D3, a Secosteroid Produced in Humans, Is Anti-Inflammatory and Inhibits Murine Autoimmune Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Arnold E. Postlethwaite ◽  
Robert C. Tuckey ◽  
Tae-Kang Kim ◽  
Wei Li ◽  
Syamal K. Bhattacharya ◽  
...  
Keyword(s):  
T Cells ◽  
Inflammatory Cytokines ◽  
Lymphocyte Subsets ◽  
Clinical Signs ◽  
Joint Damage ◽  
Type Ii Collagen ◽  
Autoimmune Arthritis ◽  
Type Ii ◽  
Cytochrome P450scc ◽  
Pro Inflammatory Cytokines

The ability to use large doses of vitamin D3 (D3) to chronically treat autoimmune diseases such as rheumatoid arthritis (RA) is prohibitive due to its calcemic effect which can damage vital organs. Cytochrome P450scc (CYP11A1) is able to convert D3 into the noncalcemic analog 20S-hydroxyvitamin D3 [20S(OH)D3]. We demonstrate that 20S(OH)D3 markedly suppresses clinical signs of arthritis and joint damage in a mouse model of RA. Furthermore, treatment with 20S(OH)D3 reduces lymphocyte subsets such as CD4+ T cells and CD19+ B cells leading to a significant reduction in inflammatory cytokines. The ratio of T reg cells (CD4+CD25+Foxp3+ T cells) to CD3+CD4+ T cells is increased while there is a decrease in critical complement-fixing anti-CII antibodies. Since pro-inflammatory cytokines and antibodies against type II collagen ordinarily lead to destruction of cartilage and bone, their decline explains why arthritis is attenuated by 20(OH) D3. These results provide a basis for further consideration of 20S(OH)D3 as a potential treatment for RA and other autoimmune disorders.

scholarly journals Comparison of the effects of triamcinolone acetonide or platelet-rich plasma on expression of extracellular matrix-related genes in equine healthy chondrocytes in vitro

2019 ◽  
Vol 49 (7) ◽  
Author(s):  
Heloisa Einloft Palma ◽  
Miguel Gallio ◽  
Gabriele Biavaschi da Silva ◽  
Camila Cantarelli ◽  
Kalyne Bertolin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Collagen Synthesis ◽  
Platelet Rich Plasma ◽  
Joint Damage ◽  
Type Ii Collagen ◽  
Control Group ◽  
Type Ii ◽  
Healthy Cartilage ◽  
Pro Inflammatory Cytokines

ABSTRACT: In healthy cartilage, chondrocytes maintain an expression of collagens and proteoglycans and are sensitive to growth factors and cytokines that either enhance or reduce type II collagen synthesis. In osteoarthritis, pro-inflammatory cytokines, such as IL-6, induce overexpression of metalloproteinases (MMP) and decreasing synthesis of aggrecan. Use of chondroprotectors agents, such as Platelet-Rich Plasma (PRP) and triamcinolone (TA) are alternatives to reduce the progression of joint damage. In this study, we used chondrocytes extracted from metacarpophalangeal joints of healthy horses as the experimental model. Cells were treated in vitro with PRP or TA. No differences were observed between these treatments in comparison to the control group when the expressions of MMP9, MMP13, IL-6 and ACAN genes were evaluated (P<0.05). With these results, we can suggest that the treatments were not deleterious to equine cultured chondrocyte, once they did not stimulate MMPs and IL-6 synthesis or caused changes in ACAN.

scholarly journals Characterization of inhibitory T cells induced by an analog of type II collagen in an HLA-DR1 humanized mouse model of autoimmune arthritis

2012 ◽  
Vol 14 (3) ◽  
pp. R107 ◽  
Author(s):  
Masaru Kimata ◽  
David L Cullins ◽  
Monica L Brown ◽  
David D Brand ◽  
Edward F Rosloniec ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Type Ii Collagen ◽  
Autoimmune Arthritis ◽  
Type Ii ◽  
Humanized Mouse ◽  
Humanized Mouse Model

scholarly journals T cells stimulated with an analog peptide of type II collagen require the Fc receptor γ-chain to secrete interleukin-4 and suppress autoimmune arthritis in mice

2011 ◽  
Vol 63 (9) ◽  
pp. 2661-2670 ◽  
Author(s):  
Linda K. Myers ◽  
David L. Cullins ◽  
David D. Brand ◽  
Sandra Kleinau ◽  
John M. Stuart ◽  
...  
Keyword(s):  
T Cells ◽  
Type Ii Collagen ◽  
Fc Receptor ◽  
Interleukin 4 ◽  
Autoimmune Arthritis ◽  
Type Ii ◽  
Analog Peptide

scholarly journals Anti-arthritic effect of total anthraquinone from Polygonum cuspidatum on type II collagen-induced arthritis in rats

2017 ◽  
Vol 16 (10) ◽  
pp. 2453-2459
Author(s):  
Feng Wang ◽  
Yan-hong Qiao ◽  
Hui-min Niu ◽  
Hong Zhao
Keyword(s):  
Inflammatory Cytokines ◽  
Type Ii Collagen ◽  
Serum Levels ◽  
Underlying Mechanism ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type Ii ◽  
Polygonum Cuspidatum ◽  
Collagen Induced Arthritis ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Purpose: To study the anti-arthritic effect of total anthraquinone from Polygonum  cuspidatum (TAPC) on type II collagen-induced arthritis (CIA) in rats, and to  investigate the underlying mechanism(s).Methods: CIA rats were prepared and treated orally with TAPC at doses of 50, 100 and 200 mg/kg/day, for 24 days. Paw volume and arthritis score were measured prior to TAPC treatment, and subsequently at 3-day intervals on days 3, 6, 9, 12, 15, 18, 21 and 24. Serum levels of TNF-α, IL-6 and IL-17 were determined by enzyme-linked immunosorbent assay (ELISA), while synovial tissue TNF-α, IL-6 and IL-17mRNA expressions were assayed by real time-polymerase chain reaction (RT-PCR). Thymus and spleen indices were also determined.Results: TAPC (50, 100 and 200 mg/kg) significantly alleviated paw swelling (p < 0.05), arthritis scores (p < 0.05) and thymus and spleen indices (p < 0.05) of CIA rats, when compared with the control rats. In addition, TAPC significantly decreased serum levels of the pro-inflammatory cytokines TNF-α, IL-6 and IL-17 (p < 0.01); and down-regulated their mRNA expressions in synovial tissues (p < 0.01).Conclusion: These results suggest that TAPC exerts good anti-arthritic activity in rats, most probably via suppression of inflammatory responses.Keywords: Polygonum cuspidatum, Anthraquinone, Type II collagen-induced  arthritis, Pro-inflammatory cytokines

PART III. AutoimmunityAn Altered Peptide Ligand of Type II Collagen Suppresses Autoimmune Arthritis

2007 ◽  
Vol 27 (4) ◽  
pp. 345-356 ◽  
Author(s):  
Linda K. Myers ◽  
Bo Tang ◽  
Edward F. Rosioniec ◽  
John M. Stuart ◽  
Andrew H. Kang
Keyword(s):  
Type Ii Collagen ◽  
Peptide Ligand ◽  
Autoimmune Arthritis ◽  
Altered Peptide Ligand ◽  
Type Ii

scholarly journals Dexamethasone Preconditioning Improves the Response of Collagen-Induced Arthritis to Treatment with Short-Term Lipopolysaccharide-Stimulated Collagen-Loaded Dendritic Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Corina Peña ◽  
David Gárate ◽  
Juan Contreras-Levicoy ◽  
Octavio Aravena ◽  
Diego Catalán ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Combined Treatment ◽  
Type Ii Collagen ◽  
Cytokine Profile ◽  
Clinical Disease ◽  
Type Ii ◽  
Collagen Induced Arthritis ◽  
Short Term

Background. Pharmacologically modulated dendritic cells (DCs) have been shown to restore tolerance in type II collagen-(CII-) induced arthritis (CIA). We examined the effect of dexamethasone (DXM) administration as a preconditioning agent, followed by an injection of lipopolysaccharide-(LPS-) stimulated and CII-loaded DCs on the CIA course.Methods. After CIA induction, mice pretreated with DXM were injected with 4-hour LPS-stimulated DCs loaded with CII (DXM/4hLPS/CII/DCs).Results. Mice injected with DXM/4hLPS/CII/DCs displayed significantly less severe clinical disease compared to animals receiving 4hLPS/CII/DCs alone or those in which only DXM was administered. Cytokine profile evaluation showed that CD4+ T cells from DXM/4hLPS/CII/DCs and 4hLPS/CII/DCs groups release higher IL-10 levels than those from mice receiving DXM alone or CIA mice. CD4+ T cells from all DC-treated groups showed less IL-17 release when compared to the CIA group. On the contrary, CD4+ T cells from DXM/4hLPS/CII/DCs and 4hLPS/CII/DCs groups released higher IFN-γlevels than those from CIA group.Conclusion. A combined treatment, including DXM preconditioning followed by an inoculation of short-term LPS-stimulated CII-loaded DCs, provides an improved strategy for attenuating CIA severity. Our results suggest that this benefit is driven by a modulation in the cytokine profile secreted by CD4+ T cells.

Abstract 252: Interleukin-27 Signaling Regulates Myeloid Cells Activation in Atherosclerosis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Iuliia Peshkova ◽  
Aliia Fatkhullina ◽  
Ekaterina Koltsova
Keyword(s):  
T Cells ◽  
T Cell ◽  
Inflammatory Cytokines ◽  
Antigen Presenting Cells ◽  
Atherosclerotic Lesions ◽  
Mediators Of Inflammation ◽  
Antigen Presenting ◽  
Deficient Mice ◽  
Pro Inflammatory Cytokines

Atherosclerosis is a lipid-driven inflammatory disease characterized by the progressive plaque growth in the vessels. Cytokines are important mediators of inflammation and atherosclerosis. While pro-inflammatory cytokines were extensively investigated, little is known about the role of anti-inflammatory cytokines as to their ability to control vascular inflammation. We tested whether immunoregulatory IL-27R signaling is important to control inflammation in mouse models of atherosclerosis. We found that atherosclerosis-prone mice with hematopoietic deficiency of IL-27R ( Ldlr -/- mice reconstituted with bone marrow from Il27ra -/- ) or global deficiency ( Il27ra -/- x Apoe -/- ) developed significantly larger atherosclerotic lesions compared to controls. Atherosclerotic lesions in IL-27R deficient mice contained more CD45 + leukocytes and CD4 + T cells, which produced pro-atherogenic cytokines IL-17A and TNF-α. These cytokines normally suppressed by IL-27, regulated the expression of CCL2 and other chemokines, which in turn led to accumulation of myeloid CD11b + and CD11c + cells in atherosclerotic aortas. Using two-photon microscopy, we found enhanced interactions between antigen presenting cells and T cells in the aortas of IL-27R deficient mice accompanied by enhanced CD4 T cell proliferation. Moreover, macrophages in Il27ra -/- aortas also demonstrated enhanced ability to produce pro-inflammatory cytokines, including IL-1. The blockade of IL-1R signaling, however, strongly suppressed atherosclerosis progression in IL-27R deficient but not control mice, suggesting an important role of IL-27 in the regulation of IL-1 production in atherosclerosis. Overall, our data demonstrate that IL-27R signaling in atherosclerosis is required to control function of antigen presenting cells modulating subsequent T cell activation in the aortas. Moreover, it controls macrophage activation and pro-inflammatory myeloid cell-derived cytokine production. These mechanisms altogether curb pathogenic T cell lineage differentiation and, thus, atherosclerosis, suggesting potent anti-atherogenic role of IL-27.

T cells are involved in the development of arthritis induced by anti-type II collagen antibody

2007 ◽  
Vol 7 (10) ◽  
pp. 1360-1368 ◽  
Author(s):  
Mana Mitamura ◽  
Nami Nakano ◽  
Taeko Yonekawa ◽  
Lihua Shan ◽  
Toshihiko Kaise ◽  
...  
Keyword(s):  
T Cells ◽  
Type Ii Collagen ◽  
Type Ii
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