The Expression of ST2 Gene in Helper T Cells and the Binding of ST2 Protein to Myeloma-Derived RPMI8226 Cells

Yanagisawa, Ken; Naito, Yoshiyuki; Kuroiwa, Kenji; Arai, Takao; Furukawa, Yusuke; Tomizuka, Hiroshi; Miura, Yasusada; Kimura, Tadashi; Tetsuka, Tsunao; Tominaga, Shin Ichi

doi:10.1093/oxfordjournals.jbchem.a021577

Cited by 99 publications

(76 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…ST2L expresses on mast cells, macrophages and exclusively on Type 2 T-helper cells [133][134][135][136][137][138][139][140]. Upon binding to ST2L, IL-33 is capable of stimulating the Th2 immune response and cytokine production [141][142][143][144].…”

Section: Introductionmentioning

confidence: 99%

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Stampalija

Chaiworapongsa

Romero

et al. 2013

The Journal of Maternal-Fetal & Neonatal Medicine

View full text Add to dashboard Cite

Objectives: Angiogenic/anti-angiogenic factors have emerged as one of the promising biomarkers for the prediction of preeclampsia. Since not all patients with preeclampsia can be identified by these analytes, the search for additional biomarkers continues. The soluble form of ST2 (sST2), a protein capable of binding to interleukin (IL)-33 and thus contributing to a Th1-biased immune response, has been reported to be elevated in maternal plasma of women with preeclampsia. The aims of this study were to examine: (1) differences in maternal plasma concentrations of sST2 and IL-33 between women diagnosed with preeclampsia and those having uncomplicated pregnancies; (2) the relationship between sST2, umbilical and uterine artery Doppler velocimetry, and the severity of preeclampsia; and (3) the performance of sST2 and angiogenic/anti-angiogenic factors in identifying patients with preeclampsia at the time of diagnosis. Methods: This cross-sectional study included women with preeclampsia (n ¼ 106) and women with an uncomplicated pregnancy (n ¼ 131). Plasma concentrations of sST2, IL-33, soluble vascular endothelial growth factor receptor (sVEGFR)-1, soluble endoglin (sEng) and placental growth factor (PlGF) were determined by enzyme linked immune sorbent assay. Area under the receiver operating characteristic curve (AUC) for the identification of preeclampsia was examined for each analyte. Results: (1) Patients with preeclampsia had a higher mean plasma concentrations of sST2 than those with an uncomplicated pregnancy (p50.0001), while no significant difference in the mean plasma concentration of IL-33 between the two groups was observed; (2) the magnitude of this difference was greater in early-onset, compared to late-onset disease, and in severe compared to mild preeclampsia; (3) sST2 plasma concentrations did not correlate with the results of uterine or umbilical artery Doppler velocimetry (p ¼ 0.7 and p ¼ 1, respectively) among women with preeclampsia; (4) sST2 correlated positively with plasma concentrations of sVEGFR1-1 and sEng (Spearman's Rho ¼ 0.72 and 0.63; each p50.0001), and negatively with PlGF (Spearman's Rho ¼ À0.56, p50.0001); and (5) while the AUC achieved by sST2 and angiogenic/anti-angiogenic factors in identifying women with preeclampsia at the time of diagnosis were non-significantly different prior to term (537 weeks of gestation), thereafter the AUC achieved by sST2 was significantly less than that achieved by angiogenic/anti-angiogenic factors. Conclusions: Preeclampsia is associated with increased maternal plasma concentrations of sST2. The findings that sST2 concentrations do not correlate with uterine or umbilical artery Doppler velocimetry in women with preeclampsia suggest that elevated maternal plasma sST2 concentrations in preeclampsia are not related to the increased impedance to flow in the uteroplacental circulation. The performance of sST2 in identifying preeclampsia at the time of diagnosis prior to 37 weeks of gestation was comparable to that of angiogenic/anti-angiogenic f...

show abstract

Section: Introductionmentioning

confidence: 99%

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Stampalija

Chaiworapongsa

Romero

et al. 2013

The Journal of Maternal-Fetal & Neonatal Medicine

View full text Add to dashboard Cite

show abstract

“…The expression of the three forms has been detected in various human tissues and cells, including hematopoietic and endothelial cells [25]. ST2L has been proposed as a marker for Th2 CD4+ T cells since it is selectively expressed on Th2 but not on Th1 CD4+ T cells [26,27] and might be involved in the effector phase of Th2 immune responses [28]. Expression of sST2 protein can be induced in vitro by pro-inflammatory stimuli, like lipo-polysaccaride (LPS), IL-1β, TNF-α and IL-6 in human and murine inflammatory models [25,29].…”

Section: Introductionmentioning

confidence: 99%

Elevated levels of soluble ST2 protein in dengue virus infected patients

et al. 2008

View full text Add to dashboard Cite

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.

show abstract

“…It was subsequently found to be expressed by mast cells (4) and by Th2, but not Th1, cells (5)(6)(7). Although ST2/T1 is a member of the IL-1R family, it does not bind IL-1␣, IL-1␤, or IL-1R antagonist (8,9).…”

mentioning

confidence: 99%

A Novel Pathway Regulating Lipopolysaccharide-Induced Shock by ST2/T1 Via Inhibition of Toll-Like Receptor 4 Expression

Sweet

Leung

Kang

et al. 2001

The Journal of Immunology

236

205

View full text Add to dashboard Cite

ST2/ST2L, a member of the IL-1R gene family, is expressed by fibroblasts, mast cells, and Th2, but not Th1, cells. It exists in both membrane-bound (ST2L) and soluble forms (ST2). Although ST2L has immunoregulatory properties, its ligand, cellular targets, and mode of action remain unclear. Using a soluble ST2-human IgG fusion protein, we demonstrated that ST2 bound to primary bone marrow-derived macrophages (BMM) and that this binding was enhanced by treatment with LPS. The sST2 treatment of BMMs inhibited production of the LPS-induced proinflammatory cytokines IL-6, IL-12, and TNF-α but did not alter IL-10 or NO production. Treatment of BMMs with sST2 down-regulated expression of Toll-like receptors-4 and -1 but induced nuclear translocation of NF-κB. Administration of sST2 in vivo after LPS challenge significantly reduced LPS-mediated mortality and serum levels of IL-6, IL-12, and TNF-α. Conversely, blockade of endogenous ST2 through administration of anti-ST2 Ab exacerbated the toxic effects of LPS. Thus, ST2 has anti-inflammatory properties that act directly on macrophages. We demonstrate here a novel regulatory pathway for LPS-induced shock via the ST2-Toll-like receptor 4 route. This may be of considerable therapeutic potential for reducing the severity and pathology of inflammatory diseases.

show abstract

The Expression of ST2 Gene in Helper T Cells and the Binding of ST2 Protein to Myeloma-Derived RPMI8226 Cells

Cited by 99 publications

References 33 publications

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Elevated levels of soluble ST2 protein in dengue virus infected patients

A Novel Pathway Regulating Lipopolysaccharide-Induced Shock by ST2/T1 Via Inhibition of Toll-Like Receptor 4 Expression

Contact Info

Product

Resources

About