The role of interleukin-17 in mediating joint destruction in rheumatoid arthritis

Li, Xia; Yuan, Feng-Lai; Lü, Weiguo; Zhao, Yiqing; Li, Chengwan; Li, Jianping; Xu, Ruirong

doi:10.1016/j.bbrc.2010.05.111

Cited by 81 publications

(53 citation statements)

References 58 publications

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“…Highly active proinflammatory cytokines, such as tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) initiate a cascade of events that results in pain and frank tissue damage in chronic inflammatory diseases of the joints. T cells and the cytokines IL-17A and TNFα have been shown to activate RA synovial fibroblasts (RASF), resulting in the expression of proinflammatory cytokines such as IL-6 and IL-8, mediators of joint bone and cartilage destruction, which induce persistent synthesis of proinflammatory cytokines and matrix metalloproteinases (MMPs) in the joint (5,6,7,8).…”

Section: Introductionmentioning

confidence: 99%

HDAC Inhibition in Rheumatoid Arthritis and Juvenile Idiopathic Arthritis

Vojinović

Damjanov²

2011

Mol Med

104

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Section: Introductionmentioning

confidence: 99%

HDAC Inhibition in Rheumatoid Arthritis and Juvenile Idiopathic Arthritis

Vojinović

Damjanov²

2011

Mol Med

104

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“…In IL-1-driven arthritis models such as collagen-induced arthritis, blockade of IL-17 is highly effective in inhibiting inflammation and structural damage to cartilage and bone [30][31][32][33][34][35]. Moreover, IL-17, like IL-1 can elicit cartilage degradation alone or in combination with other cytokines [36,37].…”

mentioning

confidence: 99%

Anti IL‐17A therapy inhibits bone loss in TNF‐α‐mediated murine arthritis by modulation of the T‐cell balance

et al. 2011

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Tumour necrosis factor alpha (TNF-a) is a major inducer for inflammation and bone loss. Here, we investigated whether interleukin (IL)-17 plays a role in TNF-a-mediated inflammation and bone resorption. Human TNF-a transgenic (hTNFtg) mice were treated with a neutralizing anti-IL-17A antibody and assessed for inflammation, cartilage and bone damage. T-cell transcription factors and lymphokine patterns were measured in the LNs. IL-17A inhibition in the absence of IL-1 was also evaluated by treating hTNFtg/IL-1 À/À mice with an IL-17A neutralizing antibody. IL-17A neutralization had only minor effects on TNF-a-induced inflammation but effectively reduced local and systemic bone loss by blocking osteoclast differentiation in vivo. Effects were based on a shift to bone-protective T-cell responses such as enhanced Th2 differentiation, IL-4 and IL-12 expression and Treg cell numbers. Whereas inflammation in hTNFtg/IL-1 À/À mice was highly sensitive to IL-17A blockade, no shift in the T-cell lineages and no additional benefit on bone mass were observed in response to IL-17A neutralization. We thus conclude that IL-17A is a key mediator of TNF-a-induced bone loss by closely interacting with IL-1 in blocking bone protective T-cell responses.Key words: Arthritis . Cytokine . IL-17 . Osteoclast . T cells IntroductionBone is continuously remodelled in life by the interaction between bone resorbing cells, termed osteoclasts, with boneforming cells, termed osteoblasts [1]. Bone resorption and bone formation are usually in physiological balance, maintaining a stable bone mass. An imbalance between bone resorption and bone formation leads to bone loss and several factors such as age, oestrogen deficiency or drug therapy alter this fine balance between osteoclasts and osteoblasts in favour of the former. Immune activation and inflammation is one the pivotal condi-Ã These authors contributed equally to this work. 413tions perturbing this fine balance of bone remodelling ultimately leading to enhanced bone loss [2]. Autoimmune inflammatory diseases, such as chronic arthritis are characterized by activation of the innate and adaptive immune system eliciting profound local and systemic bone loss. Progressive destruction of the joints is associated with pain, functional impairment and low quality of life. In addition, loss of systemic bone mass causes osteoporosis and increased fracture risk in patients with inflammatory arthritis [3]. This tight link between inflammation and bone loss is mediated by inducible expression of factors, such as M-CSF and RANKL, which are essential for osteoclast differentiation [4]. In addition, inflammatory cytokines produced by monocytes and resident mesenchymal cells are of key importance for osteoclast formation, as they regulate expression of RANKL and also sensitize monocytes for osteoclast differentiation. In this context, TNF-a, and IL-1 are of particular key importance for osteoclast formation and bone resorption in inflammatory tissue [5,6].Aside from classical pro-inflammatory mediators like ...

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“…IL-17 acts independently of TNF and IL-1 in humans, which might suggest a therapeutic role for its inhibition 13 . In animal models, and in humans, there is evidence that both Th17 cells and the IL-17 they produce contribute to cartilage and bone damage 14,15 . In fact, intraarticular injections of IL-17 generate joint damage in murine knees 16 .…”

Section: Rheumatologymentioning

confidence: 99%

Of Mice and Men: Defining the Role of Interleukin 17 in Rheumatoid Arthritis

Ruderman

2015

J Rheumatol

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The role of interleukin-17 in mediating joint destruction in rheumatoid arthritis

Cited by 81 publications

References 58 publications

HDAC Inhibition in Rheumatoid Arthritis and Juvenile Idiopathic Arthritis

HDAC Inhibition in Rheumatoid Arthritis and Juvenile Idiopathic Arthritis

Anti IL‐17A therapy inhibits bone loss in TNF‐α‐mediated murine arthritis by modulation of the T‐cell balance

Of Mice and Men: Defining the Role of Interleukin 17 in Rheumatoid Arthritis

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