TNF blockade requires 1,25(OH)2D3 to control human Th17-mediated synovial inflammation

Hamburg, Jan Piet van; Asmawidjaja, Patrick S.; Davelaar, Nadine; Mus, Anne‐Marie; Cornelissen, Ferry; Leeuwen, Johannes P.T.M. van; Hazes, Johanna M. W.; Dolhain, Radboud J E M; Bakx, Pieter A. G. M.; Colin, Edgar M.; Lubberts, Erik

doi:10.1136/annrheumdis-2011-200424

Cited by 79 publications

(59 citation statements)

References 43 publications

(57 reference statements)

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“…66 The importance of understanding the role of vitamin D in autoimmune diseases is enforced by the very high prevalence of hypovitaminosis D in this particular setting. 61,67 Relative hypovitaminosis D and secondary hyperparathyroidism in autoimmune rheumatic diseases An impairment of Vitamin D system has already been postulated as a concausal factor in the pathogenesis of osteoporosis in inflammatory arthritis.…”

Section: Vitamin D In Autoimmune Diseasesmentioning

confidence: 99%

Osteoporosis in rheumatoid arthritis: role of the vitamin D/parathyroid hormone system

Bellan

Pirisi

Sainaghi

2015

Revista Brasileira de Reumatologia (English Edition)

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RBRE-172; No. of Pages 8 r e v b r a s r e u m a t o l . 2 0 1 4;x x x(x x):xxx-xxx REVISTA BRASILEIRA DE REUMATOLOGIA w w w . r e u m a t o l o g i a . c o m . b r Available online xxx Keywords: Cholecalciferol PTH Osteoporosis Rheumatoid arthritis a b s t r a c t Osteoporosis is a well-established extra-articular feature of rheumatoid arthritis (RA). Systemic inflammation seems to play a crucial role in causing an alteration of multiple homeostatic systems implied in bone health, such as the RANK/RANKL/Osteoprotegerin and Wnt/␤ catenin pathways; several other causal factors have been called into question, including the chronic use of corticosteroids. Since vitamin D exerts important immune-regulatory roles, it has been claimed that derangement of the vitamin D/parathyroid hormone (PTH)system, a well-known determinant of bone health, may play a pathogenic role in autoimmunity; animal models and clinical data support this hypothesis. Furthermore, RA patients seem to be relatively refractory to vitamin D-induced PTH suppression. Therefore, the link between RA and osteoporosis might in part be due to alterations in the vitamin D/PTH system. A better understanding of the pathophysiology of this system may be crucial to prevent and cure osteoporosis in patients with inflammatory/autoimmune diseases. A major clinical correlate of the strict cooperation and interdependence between vitamin D and PTH is that correction of the vitamin D deficiency, at least in autoimmune diseases, should be targeted to PTH suppression. Osteoporose na artrite reumatoide: papel do sistema vitamina D/HPTPalavras chave: Colecalciferol HPT Osteoporose Artrite reumatoide r e s u m o A osteoporose é uma característica extra-articular bem estabelecida da artrite reumatoide (AR). A inflamação sistêmica parece ser essencial para causar uma alteração em múltiplos sistemas homeostáticos implicados na saúde óssea, como as vias RANK/RANKL/osteoprotegerina e Wnt/␤ catenina; vários outros fatores causais têm sido implicados, como o uso crônico de corticosteroides. Como a vitamina D exerce funç ões RBRE-172; No. of Pages 8 2 r e v b r a s r e u m a t o l . 2 0 1 4;x x x(x x):xxx-xxx imunorreguladoras importantes, tem-se afirmado que o desarranjo do sistema vitamina D/hormônio paratireóideo (HPT), um determinante bem conhecido da saúde óssea, pode desempenhar um papel patogênico na autoimunidade; estudos com animais e dados clíni-cos apoiam essa hipótese. Além disso, os pacientes com AR parecem ser relativamente refratários à supressão de HPT induzida pela vitamina D. Portanto, a ligação entre a AR e a osteoporose pode ser em parte causada por alteraç ões no sistema vitamina D/HPT. Uma melhor compreensão da fisiopatologia desse sistema pode ser crucial para prevenir e curar a osteoporose em pacientes com doenças inflamatórias/autoimunes. A maior evidência da correlação clínica de cooperação e interdependência entre a vitamina D e o HPT é que a correção da deficiência de vitamina D, pelo menos nas doenças autoimunes, deve ser orientada para a supressão do H...

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Section: Vitamin D In Autoimmune Diseasesmentioning

confidence: 99%

Osteoporosis in rheumatoid arthritis: role of the vitamin D/parathyroid hormone system

Bellan

Pirisi

Sainaghi

2015

Revista Brasileira de Reumatologia (English Edition)

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“…Recently, we showed that besides IL-17A, TNF-a was involved in the induction of the proinflammatory loop in Th17-RASF cultures (18,19). Furthermore, the combination of TNF-a and IL-17A blockade more strongly suppressed IL-6, IL-8, MMP-1, and MMP-3 production in these Th17-RASF cultures than blocking only IL-17A or only TNF-a (18).…”

Section: Combining Celecoxib and Tnf-a Blockade In Th17-rasf Culturesmentioning

confidence: 99%

“…This loop may be an important pathway in the progression of arthritis and possibly in other Th17 diseases as well. The autocrine IL-17A production by Th17 cells is critical to sustain the proinflammatory loop (18,19), but the mechanism underlying the autocrine IL-17A induction is still unknown.…”

mentioning

confidence: 99%

Synovial Fibroblasts Directly Induce Th17 Pathogenicity via the Cyclooxygenase/Prostaglandin E2 Pathway, Independent of IL-23

Paulissen

Hamburg

Davelaar

et al. 2013

The Journal of Immunology

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Th17 cells are critically involved in autoimmune disease induction and severity. Recently, we showed that Th17 cells from patients with rheumatoid arthritis (RA) directly induced a proinflammatory loop upon interaction with RA synovial fibroblasts (RASF), including increased autocrine IL-17A production. To unravel the mechanism driving this IL-17A production, we obtained primary CD4+CD45RO+CCR6+ (Th17) cells and CD4+CD45RO+CCR6− (CCR6−) T cells from RA patients or healthy individuals and cocultured these with RASF. IL-1β, IL-6, IL-23p19, and cyclooxygenase (COX)-2 expression and PGE2 production in Th17–RASF cultures were higher than in CCR6− T cell–RASF cultures. Cytokine neutralization showed that IL-1β and IL-6, but not IL-23, contributed to autocrine IL-17A induction. Importantly, treatment with celecoxib, a COX-2 inhibitor, resulted in significantly lower PGE2 and IL-17A, but not IFN-γ, production. Combined celecoxib and TNF-α blockade more effectively suppressed the proinflammatory loop than did single treatment, as shown by lower IL-6, IL-8, matrix metalloproteinase-1 and matrix metalloproteinase-3 production. These findings show a critical role for the COX-2/PGE2 pathway in driving Th17-mediated synovial inflammation in an IL-23– and monocyte-independent manner. Therefore, it would be important to control PGE2 in chronic inflammation in RA and potentially other Th17-mediated autoimmune disorders.

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“…However, when an inflammatory response occurs, FLS become hyperplastic, invasive, and highly migratory, contributing to cartilage destruction and thus, RA [6, 7]. Van Hamburg et al reported that the combination of neutralizing TNF activity and 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ) contribute to controlling human Th17 activity, which induces a pro-inflammatory feedback loop on RA synovial fibroblast interactions and inhibits synovial inflammation [8]. However, the specific mechanism of this function requires a further investigation.…”

Section: Introductionmentioning

confidence: 99%

Effect of 1,25-(OH)2D3 on Proliferation of Fibroblast-Like Synoviocytes and Expressions of Pro-Inflammatory Cytokines through Regulating MicroRNA-22 in a Rat Model of Rheumatoid Arthritis

Fan

He²,

Hu³

et al. 2017

Cell Physiol Biochem

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Objective: This study aims to investigate the regulatory mechanism of 1,25-(OH)₂D₃ on the proliferation of fibroblast-like synoviocytes (FLS) and expressions of pro-inflammatory cytokines in rheumatoid arthritis (RA) rats via microRNA-22 (miR-22). Methods: A rat model of RA was established with a subcutaneous injection of type II collagen. After treated with different concentrations of 1,25-(OH)₂D₃ the proliferation of FLS was estimated by the MTT method, and the optimal concentration of 1,25-(OH)₂D₃ was selected for further experiments. Cell proliferation was detected by MTT. Cell cycle and apoptosis were analyzed by FCM. The IL-1β, IL-6, IL-8, and PGE2 protein expressions were determined by ELISA, and MMP-3, INOS, and Cox-2 mRNA expressions were measured by qRT-PCR. Results: The rat model of RA was successfully established. Compared with the blank group, the 1,25-(OH)₂D₃ and miR-22 inhibitors groups exhibited higher proliferation inhibition and apoptosis rates, lower levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and PGE2), and decreased mRNA expressions of MMP-3, INOS, and Cox-2. The miR-22 mimics group had lower proliferation inhibition and apoptosis rates, elevated expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 than the blank group. In contrast to the 1,25-(OH)₂D₃ group, the proliferation inhibition and apoptosis rates were down-regulated, and the expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 were up-regulated in the 1,25-(OH)₂D₃ + miR-22 mimics group. Conclusion: Our study demonstrated that 1,25-(OH)₂D₃ inhibits the proliferation of FLS and alleviates inflammatory response in RA rats by down-regulating miR-22.

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TNF blockade requires 1,25(OH)2D3 to control human Th17-mediated synovial inflammation

Cited by 79 publications

References 43 publications

Osteoporosis in rheumatoid arthritis: role of the vitamin D/parathyroid hormone system

Osteoporosis in rheumatoid arthritis: role of the vitamin D/parathyroid hormone system

Synovial Fibroblasts Directly Induce Th17 Pathogenicity via the Cyclooxygenase/Prostaglandin E2 Pathway, Independent of IL-23

Effect of 1,25-(OH)2D3 on Proliferation of Fibroblast-Like Synoviocytes and Expressions of Pro-Inflammatory Cytokines through Regulating MicroRNA-22 in a Rat Model of Rheumatoid Arthritis

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