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Journal ArticleDOI

Measurement of interleukin-33 (IL-33) and IL-33 receptors (sST2 and ST2L) in patients with rheumatoid arthritis.

01 Sep 2011-Journal of Korean Medical Science (Korean Academy of Medical Sciences)-Vol. 26, Iss: 9, pp 1132-1139
TL;DR: IL-33 is involved in the pathogenesis of RA and may reflect the degree of inflammation in patients with RA, and the levels of IL-33, sST2 and C-reactive protein decreased after conventional disease-modifying antirheumatic drugs treatment in 10 patients with treatment-naïve RA.
Abstract: The interleukin-33 (IL-33)/ST2 pathway has emerged as an intercellular signaling system that participates in antigen-allergen response, autoimmunity and fibrosis. It has been suggested that IL-33/ST2 signaling has been involved in the pathogenesis of rheumatoid arthritis (RA), because IL-33 and its receptor have been specifically mapped to RA synovium. The aim of this study was to determine the levels of IL-33 and sST2 in sera and synovial fluids in patients with RA. The serum level of IL-33 was significantly higher in patients with RA (294.9 ± 464.0 pg/mL) than in healthy controls (96.0 ± 236.9 pg/mL, P = 0.002). The synovial fluid level of IL-33 was significantly higher in RA patients than in osteoarthritis patients. The level of serum sST2 was higher in RA patients than in healthy controls (P = 0.042). A significant relationship was found between the levels of IL-33 and IL-1β (r = 0.311, P = 0.005), and IL-33 and IL-6 (r = 0.264, P = 0.017) in 81 RA patients. The levels of IL-33, sST2 and C-reactive protein decreased after conventional disease-modifying antirheumatic drugs treatment in 10 patients with treatment-naive RA. Conclusively, IL-33 is involved in the pathogenesis of RA and may reflect the degree of inflammation in patients with RA.

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Citations
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Journal ArticleDOI
TL;DR: IL‐13, a helper T cell type 2 (Th2) cytokine, transforms cultured airway epithelial cells to goblet cells, and this is not inhibited by corticosteroids, and the effect of IL‐33 onGoblet cell differentiation and cytokine secretion has not been described.
Abstract: SummaryBackground IL-13, a helper T cell type 2 (Th2) cytokine, transforms cultured airway epithelial cells to goblet cells, and this is not inhibited by corticosteroids. IL-33 stimulates Th2 cytokines and is highly expressed in airways of persons with asthma. The effect of IL-33 on goblet cell differentiation and cytokine secretion has not been described. Objective We examined the effect of IL-33 on CXCL8/IL-8 secretion from goblet or normally differentiated human bronchial epithelial (NHBE) cells and signalling pathways associated with IL-33 activation in these cells. Methods Normal human bronchial epithelial cells were grown to goblet or normally differentiated ciliated cell phenotype at air–liquid interface in the presence or absence of IL-13. After 14 days, differentiated cells were exposed to IL-33 for 24 h. Results CXCL8/IL-8 secretion into the apical (air) side of the goblet cells was greater than from normally differentiated cells (P < 0.01), and IL-33 stimulated apical CXCL8/IL-8 release from goblet cells, but not from normally differentiated cells (P < 0.01). IL-33 increased ERK 1/2 phosphorylation in goblet cells (P < 0.05), and PD98059, a MAPK/ERK kinase inhibitor, attenuated IL-33-stimulated CXCL8/IL-8 secretion from goblet cells (P < 0.001). IL-13 induced ST2 mRNA (P < 0.02) and membrane-bound ST2 protein expression on the apical side surface of goblet cells compared with normally differentiated cells, and neutralization with anti-ST2R antibody attenuated IL-33-induced apical CXCL8/IL-8 secretion from goblet cells (P < 0.02). Conclusions and Clinical Relevance Goblet cells secrete CXCL8/IL-8, and this is increased by IL-33 through ST2R-ERK pathway, suggesting a mechanism for enhanced airway inflammation in the asthmatic airway with goblet cell metaplasia.

43 citations

Journal ArticleDOI
TL;DR: Recent advances on the pathological roles of IL-33 in RA are summarized and the therapeutic significance of these new findings are discussed.

42 citations

Journal ArticleDOI
TL;DR: Circulating IL-1β concentrations are clinically meaningful in ADHF patients and interplay with the predictive ability of sST2, which may represent a therapeutic target in AD HF.

41 citations

Journal ArticleDOI
TL;DR: In advanced CHF, IL-33 may exert anti-oxidation effects, which may be overwhelmed by concurrently elevated levels of sST2, which is positively correlated with markers of CHF severity.
Abstract: Background: Interleukin-33 (IL-33) has been linked to chronic heart failure (CHF) in animal studies, but data on serum IL-33 levels in human CHF are not available. We analyzed levels of IL-33 in serum, and investigated the possible role of IL-33 in oxidative stress. Methods: A total of 191 subjects with advanced systolic CHF (CHF group), 175 patients with pre-existing cardiac diseases but no CHF (non-CHF group), and 177 healthy controls (HC group) were enrolled. Serum levels of IL-33, soluble ST2 (sST2) and N-terminal-pro-brain natriuretic peptide (NT-proBNP), malondialdehyde (MDA) content, erythrocyte superoxide dismutase (eSOD) activity, as well as left ventricular ejection fraction (LVEF), were determined. The exact form of IL-33 in serum was identified. Effects of IL-33 and sST2 on MDA content and SOD activity in angiotensin (Ang II)-stimulated AC16 cells were assessed. Results: Serum levels of IL-33 and sST2 were elevated in CHF patients, whereas IL-33/sST2 ratios were decreased. In CHF patients, pre-existing cardiac diseases and medications used upon hospital admission did not affect IL-33 concentrations or the IL-33/sST2 ratio. Full-length IL-33, which could not be detected in serum from HC and barely detected in non-CHF patients, was significantly up-regulated in CHF patients. IL-33 levels were positively correlated with markers of CHF severity. IL-33/sST2 ratios were slightly and negatively related to MDA concentrations. IL-33 directly reduced MDA and enhanced SOD activity in Ang II-stimulated AC16 cells, which were greatly attenuated by sST2. Conclusions: Serum levels of IL-33, especially the full-length form, were elevated in CHF patients whereas IL-33 bioactivity was reduced. In advanced CHF, IL-33 may exert anti-oxidation effects, which may be overwhelmed by concurrently elevated levels of sST2.

40 citations


Cites background from "Measurement of interleukin-33 (IL-3..."

  • ..., fibroblasts, endothelial cells, macrophages) may be the potential sources [28-30]....

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Journal ArticleDOI
01 Nov 2017-Cytokine
TL;DR: The IL‐33‐matured DCs enhanced the expression of an early T cell activation marker (CD69) and the Th17 master transcription factor (ROR&ggr;t), but IL‐ 33 did not directly affect CD4+ T cell differentiation or increase Th17 polarization.

38 citations


Cites background from "Measurement of interleukin-33 (IL-3..."

  • ...Because IL-33 is highly expressed in endothelial cells and epithelial cells in autoimmune diseases patients [2,4,5,18], we speculated that IL-33 may affect DCs recognizing self-antigens in inflamed tissues....

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  • ...IL-33 is significantly increased in patients with a variety of autoimmune diseases [18], by being expressed in epithelial cells or synovial fibroblasts [4,5]....

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References
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Journal ArticleDOI
TL;DR: The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA).
Abstract: The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a "classification tree" schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.

19,409 citations


"Measurement of interleukin-33 (IL-3..." refers methods in this paper

  • ...RA was diagnosed based on the American College of Rheumatology 1987 criteria (13)....

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Journal Article
TL;DR: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for the rheumatic diseases to date, and these new revised classified criteria for rheumatoid arthritis are very important as they should provide understanding of the possibly changing face of rheumatism.
Abstract: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for the rheumatic diseases to date. These new revised classification criteria for rheumatoid arthritis are very important as they should provide understanding of the possibly changing face of rheumatoid arthritis.

8,645 citations

Journal ArticleDOI
01 Nov 2005-Immunity
TL;DR: A member of theIL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T( H)2 cells is reported.

3,306 citations


"Measurement of interleukin-33 (IL-3..." refers background in this paper

  • ...It also increases the production of IL-5 and IL-13 by polarized Th2 cells (3) and interferon-γ (IFN-γ) production by both iNKT and NK cells (7)....

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  • ...Mature IL-33 has been reported to mediate its biologic effects via T1/ST2 binding by activating NF-κB and MAP kinase (3)....

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  • ...The expression of ST2L, a membrane-anchored long form, is restricted to the surface of Th2 cells and mast cells (3)....

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  • ...Although recombinant pro-IL-33 is cleaved by recombinant caspase-1 in vitro (3), the in vivo role of caspase-1 in the cleavage of pro-IL-33 remains controversial (27)....

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  • ...Therefore, synovial fibroblasts, endothelial cells, activated DCs, and macrophages may be the main source of IL-33 in synovial fluid from RA patients (3, 15)....

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Journal ArticleDOI
TL;DR: The current knowledge regarding the role of proinflammatory cytokines in the pathophysiology of OA is discussed and the potential of anticytokine therapy in the treatment of this disease is addressed.
Abstract: Osteoarthritis (OA) is associated with cartilage destruction, subchondral bone remodeling and inflammation of the synovial membrane, although the etiology and pathogenesis underlying this debilitating disease are poorly understood. Secreted inflammatory molecules, such as proinflammatory cytokines, are among the critical mediators of the disturbed processes implicated in OA pathophysiology. Interleukin (IL)-1β and tumor necrosis factor (TNF), in particular, control the degeneration of articular cartilage matrix, which makes them prime targets for therapeutic strategies. Animal studies provide support for this approach, although only a few clinical studies have investigated the efficacy of blocking these proinflammatory cytokines in the treatment of OA. Apart from IL-1β and TNF, several other cytokines including IL-6, IL-15, IL-17, IL-18, IL-21, leukemia inhibitory factor and IL-8 (a chemokine) have also been shown to be implicated in OA and could possibly be targeted therapeutically. This Review discusses the current knowledge regarding the role of proinflammatory cytokines in the pathophysiology of OA and addresses the potential of anticytokine therapy in the treatment of this disease.

1,962 citations


"Measurement of interleukin-33 (IL-3..." refers background in this paper

  • ...IL-1β, TNF and IL-6 seem to be the main proinflammatory cytokines involved in the pathophysiology of OA (19)....

    [...]

Journal ArticleDOI
TL;DR: IL-33 is host-protective against helminth infection and reduces atherosclerosis by promoting TH2-type immune responses but can also promote the pathogenesis of asthma by expanding TH2 cells and mediate joint inflammation, atopic dermatitis and anaphylaxis by mast cell activation.
Abstract: Interleukin-33 (IL-33), a newly described member of the IL-1 family, is expressed by many cell types following pro-inflammatory stimulation and is thought to be released on cell lysis. The IL-33 receptor, consisting of ST2 and IL-1 receptor accessory protein, is also widely expressed, particularly by T helper 2 (T(H)2) cells and mast cells. IL-33 is host-protective against helminth infection and reduces atherosclerosis by promoting T(H)2-type immune responses. However, IL-33 can also promote the pathogenesis of asthma by expanding T(H)2 cells and mediate joint inflammation, atopic dermatitis and anaphylaxis by mast cell activation. Thus IL-33 could be a new target for therapeutic intervention across a range of diseases.

925 citations


"Measurement of interleukin-33 (IL-3..." refers background in this paper

  • ...(24) also proposed that in established RA, IL-33 causes mast cell-mediated inflammation, which amplifies the Th17 cell response....

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  • ...(24) suggested that in early RA, IL-33 produced by synovial fibroblasts and synovial endothelial cells induces a Th2-type response....

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