Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma

Brunner, Markus; Krenn, Claus G.; Roth, Georg A.; Moser, Bernhard; Dworschak, Martin; Jensen‐Jarolim, Erika; Spittler, Andreas; Sautner, Thomas; Bonaros, Nikolaos; Wolner, Ernst; Boltz‐Nitulescu, George; Ankersmit, Hendrik Jan

doi:10.1007/s00134-004-2184-x

Cited by 167 publications

(120 citation statements)

References 29 publications

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“…Serum sST2 has emerged as a marker for several types of diseases, including cardiopathy and asthma (Oshikawa et al, 2001;Tajima et al, 2003;Brunner et al, 2004;Kakkar and Lee, 2008). A fraction of our patients with metastatic breast cancer showed elevated levels of sST2.…”

Section: à4mentioning

confidence: 88%

Gene expression profiling identifies sST2 as an effector of ErbB2-driven breast carcinoma cell motility, associated with metastasis

Gillibert-Duplantier¹,

Duthey²,

Sisirak³

et al. 2011

Oncogene

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Overexpression of the ErbB2 receptor tyrosine kinase in breast cancer contributes to tumor development and is associated with poor prognosis. However, the mechanism by which ErbB2 might contribute to metastasis is not well defined. To identify genes that mediate ErbB2-driven cell motility, we performed differential gene expression analysis of ErbB2-expressing migrating breast cancer cells vs mutant ErbB2-expressing non-migrating cells. Among the genes that were specifically induced in migrating cells were known transcriptional targets of ErbB2, such as matrix metalloproteinases, and novel ErbB2 targets. Contribution of selected candidate genes to ErbB2-driven cell motility was tested by small interfering RNA targeting. Knockdown of the soluble form of ST2 (sST2), also called interleukin-1 receptor-like 1, one of the most robustly induced genes, decreased ErbB2-induced cell motility in two different cell lines. In response to ErbB2 activation, sST2 protein expression and secretion were increased. Moreover, recombinant sST2 associated with the plasma membrane and sST2-blocking antibodies reduced ErbB2-induced motility. Interestingly, cells from metastatic breast tumors secreted higher levels of sST2 than primary tumor cells. Finally, sST2 was found at high levels in the serum of metastatic breast cancer patients. Our data suggest that sST2 contributes to breast cancer cell motility and that sST2 secretion is associated with metastasis.

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Section: à4mentioning

confidence: 88%

Gene expression profiling identifies sST2 as an effector of ErbB2-driven breast carcinoma cell motility, associated with metastasis

Gillibert-Duplantier¹,

Duthey²,

Sisirak³

et al. 2011

Oncogene

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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.…”

Section: Discussionmentioning

confidence: 99%

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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“…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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Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma

Abstract: Our results demonstrate that soluble ST2, a marker for Th2 cytokine producing cells, is increased in sepsis and trauma patients, and they provide further evidence for a shift from Th1- to Th2-biased cells.

Cited by 167 publications

References 29 publications

Gene expression profiling identifies sST2 as an effector of ErbB2-driven breast carcinoma cell motility, associated with metastasis

Gene expression profiling identifies sST2 as an effector of ErbB2-driven breast carcinoma cell motility, associated with metastasis

IL‐33 is a chemoattractant for human Th2 cells

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

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