A Novel Therapy of Murine Collagen-Induced Arthritis with Soluble T1/ST2

Leung, Bernard P.; Xu, Damo; Culshaw, Shauna; McInnes, Iain B.; Liew, Foo Y.

doi:10.4049/jimmunol.173.1.145

Cited by 160 publications

(134 citation statements)

References 37 publications

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“…Increased serum levels of sST2 have been detected in a number of human diseases, including asthma and allergic airway inflammation, acute myocardial infarctions, and sepsis [10][11][12][13][14]. Although the biological significance for the increase in sST2 is not understood, several studies have demonstrated beneficial effects of sST2 treatment in animal models of diseases [2,4,6,15], suggesting that it may reduce inflammation. Intraperitoneal injection of IL-33 in mice resulted in splenomegaly, eosinophila and elevated serum IgE.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously demonstrated that treatment of mice with a soluble form of ST2 (sST2) which can neutralize the function of IL-33, significantly attenuated established septic shock [5] and collagen-induced arthritis [6]. Recently, it has been reported that IL-33 injected intraperitoneally led to splenomegaly, eosinophilia and elevated serum IgE levels.…”

Section: Introductionmentioning

confidence: 99%

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IL‐33 is a chemoattractant for human Th2 cells

et al. 2007

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IL‐33 is a novel cytokine of the IL‐1 family and mediates its biological effect via the receptor ST2, which is selectively expressed on Th2 cells but not Th1 cells. IL‐33 drives production of Th2‐associated cytokines including IL‐5 and IL‐13 and thereby promotes defense and pathology in mucosal organs. Cell locomotion is crucial to the induction of an effective immune response. We report here the chemoattraction of Th2 cells by IL‐33. Recombinant IL‐33 increased the proportion of human Th2 cells, but not Th1 cells, in polarized morphology in vitro and stimulated their subsequent invasion into collagen gels in an IL‐33 concentration‐dependent manner. Injection of recombinant IL‐33 into the footpad of ST2–/– mice which had been adoptively transferred with polarized Th2 cells, led to local accumulation of the transferred Th2 cells. These data therefore demonstrate that IL‐33 is a selective Th2 chemoattractant associated with the pro‐inflammatory property of this novel cytokine.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

IL‐33 is a chemoattractant for human Th2 cells

et al. 2007

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“…Some evidence suggests that sST2 could act as an anti-inflammatory mediator, through a mechanism that involves the inhibition of Toll-like receptor signaling by sequestration of MyD88 and Mal adapter proteins [45,46] or inhibition of I-κB degradation [47] resulting in down-regulation of NF-κB. In vitro and in vivo experiments have shown that sST2 protein or an ST2-fusion protein is able to attenuate the production of pro-inflammatory cytokines IL-1β, TNF-α, IL-6, and IL-12 [30,45,48]. In two mouse models of ischemia/reperfusion, pretreatment with an sST2-Fc fusion protein decreased the inflammatory response [49,50].…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of soluble ST2 protein in dengue virus infected patients

et al. 2008

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Levels of the soluble form of the interleukin-1 receptor like 1 protein (IL-1RL-1 / ST2) are elevated in the serum of patients with diseases characterized by an inflammatory response. The objective of this study was to determine the concentration of soluble ST2 (sST2) in dengue infected patients during the course of the disease. Twenty four patients with confirmed dengue infection, classified as dengue fever, and eleven patients with other febrile illness (OFI) were evaluated. Levels of sST2 in serum and laboratory variables usually altered during dengue infections were measured. Dengue infected patients had higher serum sST2 levels than OFI at the end of the febrile stage and at defervescence (p=0.0088 and p=0.0004 respectively). Patients with secondary dengue infections had higher serum sST2 levels compared with patients with primary dengue infections (p=0.047 at last day of fever and p=0.030 at defervescence). Furthermore, in dengue infected patients, we found a significant negative correlation of sST2 with platelet and WBC counts, and positive correlation with thrombin time and transaminases activity. We suggest that sST2 could be a potential marker of dengue infection, could be associated with severity or could play a role in the immune response in secondary dengue virus infection.

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“…4a). It has been previously reported that pre-treatment with sST2/Fc inhibits cytokine production induced by LPS in macrophages [15][16][17]. We thus examined whether sST2/Fc could also affect the response to LPS in BMMC.…”

Section: Il-33 Induces Il-6 Production By Bmmcmentioning

confidence: 99%

Interleukin (IL)-33 induces the release of pro-inflammatory mediators by mast cells

Donzé²,

et al. 2007

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IL-33 (or IL-1F11) was recently identified as a ligand for the previously orphaned IL-1 family receptor T1/ST2. Previous studies have established that IL-33 and T1/ST2 exert key functions in Th2 responses. In this study, we demonstrate that IL-33 induces the production of pro-inflammatory mediators in mast cells. IL-33 dose and time-dependently stimulated IL-6 secretion by P815 mastocytoma cells and primary mouse bone marrow-derived mast cells (BMMC). This effect was dependent on T1/ST2 binding. In addition, IL-33 also induced IL-1b, TNF-a, MCP-1, and PGD2 production in BMMC. By RNase protection assay, we demonstrated that IL-33 increased IL-6 and IL-1b mRNA expression. These effects of IL-33 appeared to occur independently of mast cell degranulation, The results of this study show for the first time that IL-33, a novel member of the IL-1 family of cytokines, stimulates the production of pro-inflammatory mediators by mast cells in addition to its effect on T helper 2 responses. These findings open new perspectives for the treatment of inflammatory diseases by targeting IL-33.

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A Novel Therapy of Murine Collagen-Induced Arthritis with Soluble T1/ST2

Cited by 160 publications

References 37 publications

IL‐33 is a chemoattractant for human Th2 cells

IL‐33 is a chemoattractant for human Th2 cells

Elevated levels of soluble ST2 protein in dengue virus infected patients

Interleukin (IL)-33 induces the release of pro-inflammatory mediators by mast cells

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