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

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.

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

Ciência Rural ◽

10.1590/0103-8478cr20180262 ◽

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.

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

Arthritis Research & Therapy ◽

10.1186/ar3832 ◽

2012 ◽

Vol 14 (3) ◽

pp. R107 ◽

Cited By ~ 7

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

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Activated Type II Collagen Reactive T Cells are not Eliminated by in vivo Anti-CD4 Treatment. Implications for Therapeutic Approaches on Autoimmune Arthritis

Immunobiology ◽

10.1016/s0171-2985(11)80593-0 ◽

1992 ◽

Vol 184 (4-5) ◽

pp. 359-371 ◽

Cited By ~ 11

Author(s):

Tom J. Goldschmidt ◽

Mikael Andersson ◽

Vivianne Malmström ◽

Rikard Holmdahl

Keyword(s):

T Cells ◽

Type Ii Collagen ◽

Autoimmune Arthritis ◽

Type Ii ◽

Therapeutic Approaches

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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

Arthritis & Rheumatism ◽

10.1002/art.30454 ◽

2011 ◽

Vol 63 (9) ◽

pp. 2661-2670 ◽

Cited By ~ 4

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

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

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v16i10.20 ◽

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

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

Critical Reviews™ in Immunology ◽

10.1615/critrevimmunol.v27.i4.40 ◽

2007 ◽

Vol 27 (4) ◽

pp. 345-356 ◽

Cited By ~ 12

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

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

Clinical and Developmental Immunology ◽

10.1155/2013/296031 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 2

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.

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Decreased pro-inflammatory cytokines and increased CCR7 expression on T-lymphocyte subsets are predictive of response to extracorporeal photopheresis in patients with GvHD

British Journal of Haematology ◽

10.1111/j.1365-2141.2010.08515.x ◽

2011 ◽

Vol 154 (3) ◽

pp. 409-413 ◽

Cited By ~ 4

Author(s):

Masayuki Aoki ◽

Viviana Marin-Esteban ◽

Roman Weigl ◽

Dominique Charron ◽

Hildegard Greinix ◽

...

Keyword(s):

Inflammatory Cytokines ◽

T Lymphocyte ◽

Lymphocyte Subsets ◽

Extracorporeal Photopheresis ◽

T Lymphocyte Subsets ◽

Ccr7 Expression ◽

Pro Inflammatory Cytokines

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

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.252 ◽

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.

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