Identification of Human ST2 Protein in the Sera of Patients with Autoimmune Diseases

Kuroiwa, Kenji; Arai, Takao; Okazaki, Hitoaki; Minota, Seiji; Tominaga, Shin‐ichi

doi:10.1006/bbrc.2001.5090

Cited by 131 publications

(89 citation statements)

References 29 publications

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“…In several disorders, serum concentrations of sST2 were elevated, [3][4][5][6][7][8][9] and the binding ability of sST2 towards IL-33 is generally thought to play a key role in the pathogenetic relevance of sST2. 2,8,23,24 IL-33 is considered to be involved in a broad spectrum of diseases: not only in Th2-related diseases such as asthma and atopic dermatitis, but also in other inflammatory diseases such as inflammatory bowel disease, type 2 diabetes, and cardiovascular diseases, in which IL-33 is thought to protect the cardiovascular system.…”

Section: St2 Inhibits Lps On Dendritic Cellsmentioning

confidence: 99%

“…2 In addition, we and other groups have reported that the serum level of sST2 rises in various diseases, including asthma, autoimmune diseases, cardiovascular diseases and sepsis, although the pathological relevance of these findings remains largely unknown. [3][4][5][6][7][8][9] Before IL-33 was revealed to be a ligand of ST2L, sST2 was reported to inhibit the production of lipopolysaccharide (LPS)-induced proinflammatory cytokines in macrophages and to reduce the LPSmediated mortality of mice. 10 Recently, acute lung injury caused by LPS was again reported to be suppressed by sST2.…”

Section: Introductionmentioning

confidence: 99%

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Soluble ST2 protein inhibits LPS stimulation on monocyte-derived dendritic cells

et al. 2012

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ST2 protein is a soluble splicing variant of ST2L protein, which is the receptor for interleukin-33 (IL-33). Previously, we reported that soluble ST2 suppressed the signal transduction of lipopolysaccharide (LPS) and cytokine production in monocytic cells. To investigate whether or not this inhibitory effect occurs in dendritic cells, which are the key players in innate and adaptive immunity, human monocyte-derived dendritic cells were pre-treated with soluble ST2 protein before LPS stimulation. Although soluble ST2 did not attenuate the LPS-induced maturation of dendritic cells, pre-treatment with soluble ST2 suppressed cytokine production and inhibited LPS signaling. Moreover, the proliferation of naive T cells was inhibited significantly by soluble ST2 pre-treatment. IL-33 had little effect on the cytokine production of immature monocyte-derived dendritic cells. Furthermore, soluble ST2 protein was internalized into dendritic cells, suggesting that soluble ST2 protein acts by a noncanonical mechanism other than the sequestration of IL-33. 1 The specific receptor for IL-33 is ST2L protein, which forms a receptor complex with IL-1 receptor accessory protein. Soluble ST2 protein (sST2) is a variant of ST2L arising from alternative splicing. Because it binds with IL-33 to sequestrate the effect of IL-33, sST2 is considered an antiinflammatory factor in cases such as asthma.2 In addition, we and other groups have reported that the serum level of sST2 rises in various diseases, including asthma, autoimmune diseases, cardiovascular diseases and sepsis, although the pathological relevance of these findings remains largely unknown.

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Section: St2 Inhibits Lps On Dendritic Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Soluble ST2 protein inhibits LPS stimulation on monocyte-derived dendritic cells

et al. 2012

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“…Serum concentrations of sST2 are elevated in patients suffering from various disorders associated with an abnormal Th2 response, such as asthma [6], as well as in inflammatory conditions that are mainly independent of a Th2 response. Indeed, increased levels of sST2 were observed in sera from patients suffering from septic shock, trauma [4,7], systemic lupus erythematosus [8] and in the synovial fluid of patients with rheumatoid arthritis, when compared to osteoarthritis patients [9]. In addition, mast cells have been recognized as important mediators of the pathogenesis of inflammatory diseases including ulcerative colitis, Crohn's disease [10], and arthritis [11].…”

Section: Introductionmentioning

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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“…In mice, the production of pro-inflammatory cytokines precedes sST2 expression [30]. Elevated levels of sST2 have been found in patients with inflammatory disorders associated with abnormal Th2 mediated responses, including autoimmune diseases [31], asthma [32,33], idiopathic pulmonary fibrosis [29], and sepsis [34]; sST2 levels are also found elevated in patients with other inflammatory conditions, like LPS induced inflammation [35] and myocardial infarction [36]. Additionally, sST2 has been proposed as a biomarker for heart failure [37].…”

Section: Introductionmentioning

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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Identification of Human ST2 Protein in the Sera of Patients with Autoimmune Diseases

Cited by 131 publications

References 29 publications

Soluble ST2 protein inhibits LPS stimulation on monocyte-derived dendritic cells

Soluble ST2 protein inhibits LPS stimulation on monocyte-derived dendritic cells

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

Elevated levels of soluble ST2 protein in dengue virus infected patients

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