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.
Citations
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TL;DR: The pathogenic role of uncontrolled JAK-STAT signaling in the aggressive and passive responses of RA-FLS that are critical for RA progression is confirmed.
28 citations
Cites result from "Measurement of interleukin-33 (IL-3..."
..., 2015), found at higher levels in the synovial fluid of RA compared with OA patients (Altobelli et al., 2017; Hong et al., 2011; Kurowska et al., 2002; Matsuyama et al., 2012; Moon et al., 2012)....
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TL;DR: It is shown that red blood cells (RBCs) are one of the major sources of plasma IL- 33 and circulating RBCs represent a major source of IL-33 that is released upon hemolysis.
Abstract: Interleukin-33 (IL-33) is a member of the IL-1 cytokine superfamily that potently drives production of a variety of cytokines and contributes to the pathogenesis of inflammatory diseases. The IL-33 is a nuclear protein and is released from apoptotic or necrotic cells. Serum IL-33 levels are increased in various diseases, such as atopic dermatitis, chronic hepatitis C infection, and asthma. Here, we show that red blood cells (RBCs) are one of the major sources of plasma IL-33. The IL-33 levels are significantly increased in supernatants from lysed RBCs. Plasma IL-33 levels are increased in patients during hemolysis, and plasma IL-33 levels show a positive correlation with degree of hemolysis. The IL-33 protein and messenger RNA levels were detected in the late stages of differentiation in ex vivo primary human erythroid progenitor cell cultures, suggesting that IL-33 is expressed during maturation of RBCs. Furthermore, hemoglobin depleted red cell lysates induced IL-8 expression in human epithelial cells. This effect was attenuated in IL-33 decoy receptor expressing cells and was enhanced in IL-33 receptor expressing cells. These results suggest that erythroid progenitor cells produce IL-33 and circulating RBCs represent a major source of IL-33 that is released upon hemolysis.
27 citations
TL;DR: IL-33 could be associated with the pathogenesis of periodontal disease after increased expression of IL-33 and RANKL compared with the healthy group and there was a positive correlation between these expressions.
Abstract: Background and Objective
Interleukin-33 (IL-33) controls T-helper type 2 (Th2) cytokines and the development of mast cells. This study aimed to investigate the expression of IL-33 and its association with RANKL and osteoprotegerin (OPG) in periodontal health and experimental periodontitis.
Material and Methods
Eighteen Wistar rats were assigned to two study groups of nine animals each: ligature only (LO) and nonligated (NL). Silk sutures were placed subgingivally, surrounding the right lower first molars. The animals were killed on day 11 after ligature placement, and the alveolar bone loss at the first molars was determined histometrically. Periodontal tissues were examined histopathologically to evaluate the differences between the groups. The expression of IL-33, RANKL and OPG was detected immunohistochemically.
Results
The LO group showed significantly greater alveolar bone loss compared with the NL group (p < 0.05). The numbers of osteoclasts, osteoblasts and inflammatory cells were significantly higher in the LO group compared with the NL group (p < 0.05). Osteoblastic activity was significantly lower in the LO group than in the NL group (p < 0.05). There was significantly higher expression of IL-33 and RANKL and a greater number of OPG-positive cells in the LO group (p < 0.05). IL-33 expression showed a positive correlation with RANKL expression and with the number of mast cells (p < 0.05).
Conclusion
The experimental periodontitis group exhibited increased expression of IL-33 and RANKL compared with the healthy group. Additionally, there was a positive correlation between these expressions. According to these results, IL-33 could be associated with the pathogenesis of periodontal disease.
27 citations
TL;DR: The clinical potential of the expression, regulation and function of IL-33/ST2 pathway in predicting disease activity and severity and offer possible future therapeutic alternatives are discussed.
26 citations
TL;DR: IL-33/sST2 may be involved in the pathogenesis of pSS and partly contribute to the ILD in pSS patients, especially in patients with ILD.
25 citations
References
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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
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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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)....
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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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