Results 1 - 10 of 28

IL-33 induces IL-13 production by mouse mast cells independently of IgE-Fc�RI signals

by Lien H. Ho, Tatsukuni Ohno, Keisuke Oboki, Naoki Kajiwara, Hajime Suto, Motoyasu Iikura, Yoshimichi Okayama, Shizuo Akira, Hirohisa Saito, Stephen J. Galli, Susumu Nakae
"... Abstract: The IL-1-related molecules, IL-1 and IL-18, can promote Th2 cytokine production by IgE/antigen-Fc�RI-stimulated mouse mast cells. Another IL-1-related molecule, IL-33, was identified recently as a ligand for T1/ST2. Although mouse mast cells constitutively express ST2, the effects of IL-33 ..."
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Abstract: The IL-1-related molecules, IL-1 and IL-18, can promote Th2 cytokine production by IgE/antigen-Fc�RI-stimulated mouse mast cells. Another IL-1-related molecule, IL-33, was identified recently as a ligand for T1/ST2. Although mouse mast cells constitutively express ST2, the effects of IL-33 on mast cell function are poorly
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SNPs in the distal promoter of the ST2 gene are associated with atopic dermatitis. Hum.Mol.Genet

by Makiko Shimizu, Akira Matsuda, Ken Yanagisawa, Tomomitsu Hirota, Mitsuteru Akahoshi, Naoko Inomata, Kouji Ebe, Keiko Tanaka, Hisashi Sugiura, Kazuko Nakashima, Mayumi Tamari, Naomi Takahashi, Kazuhiko Obara, Tadao Enomoto, Yoshimichi Okayama, Pei-song Gao, Shau-ku Huang, Shin-ichi Tominaga, Zenro Ikezawa - Tamari M., Takahashi N., Obara K., Enomoto T., Okayama Y., Gao P.S., Huang S.K., Tominaga S., Ikezawa Z., & Shirakawa T. Functional
"... Atopic dermatitis (AD) is a common inflammatory skin disease associated with the local infiltration of T helper type 2 (Th2) cells. The ST2 gene encodes both membrane-bound ST2L and soluble ST2 (sST2) proteins by alternative splicing. The orphan receptor ST2L is functionally indispensable for Th2 ce ..."
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Atopic dermatitis (AD) is a common inflammatory skin disease associated with the local infiltration of T helper type 2 (Th2) cells. The ST2 gene encodes both membrane-bound ST2L and soluble ST2 (sST2) proteins by alternative splicing. The orphan receptor ST2L is functionally indispensable for Th2 cells. We found a sig-nificant genetic association between AD and the 226999G/A single nucleotide polymorphism (SNP) (x2-test, raw P-value 5 0.000007, odds ratio 1.86) in the distal promoter region of the ST2 gene (chromosome 2q12) in a study of 452 AD patients and 636 healthy controls. The 226999A allele common among AD patients posi-tively regulates the transcriptional activity of the ST2 gene. In addition, having at least one 226999A allele correlated with high sST2 concentrations and high total IgE levels in the sera from AD patients. Thus, the 226999A allele is correlated with an increased risk for AD. We also found that the 226999G/A SNP predomi-nantly affected the transcriptional activity of hematopoietic cells. Immunohistochemical staining of a skin biopsy specimen from an AD patient in the acute stage showed ST2 staining in the keratinocytes as well
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ST2 is essential for Th2 responsiveness and resistance to pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci 48

by Xi Huang , Wenjin Du , Ronald P Barrett , Linda D Hazlett , 2007
"... PURPOSE. To elucidate the role of ST2, a member of the TLR/ IL-1R (TIR) superfamily, in protecting against Pseudomonas aeruginosa keratitis in BALB/c mice. METHODS. ST2 mRNA and protein expression levels were tested by real-time PCR and Western-blot in C57BL/6 (B6; susceptible) versus BALB/c (resis ..."
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PURPOSE. To elucidate the role of ST2, a member of the TLR/ IL-1R (TIR) superfamily, in protecting against Pseudomonas aeruginosa keratitis in BALB/c mice. METHODS. ST2 mRNA and protein expression levels were tested by real-time PCR and Western-blot in C57BL/6 (B6; susceptible) versus BALB/c (resistant) mice before and after P. aeruginosa (strain 19660; American Type Culture Collection, Philadelphia, PA) challenge. Infected BALB/c mice also were tested after subconjunctival injection with recombinant murine (rm)ST2 or PBS. Disease was monitored by clinical score, slit lamp, bacterial plate count, a myeloperoxidase (MPO) assay to measure polymorphonuclear neutrophil (PMN) infiltrate, real-time RT-PCR, and ELISA. RESULTS. ST2 mRNA and protein were constitutively expressed in the uninfected normal corneas of both mouse groups. ST2 levels in the cornea of BALB/c compared with B6 mice were elevated significantly at 1 to 3 days post infection (PI), peaked at 3 and decreased at 5 days PI. BALB/c mice treated with rmST2 showed increased corneal opacity and perforation (at 5 days PI) when compared with PBS controls. rmST2-versus PBS-injected mice exhibited increased bacterial load, PMN infiltrate, and higher corneal mRNA levels for IL-1␤, MIP-2, IL-6, IL-1R1, and Th1-type cytokine such as IFN-␥. Protein levels for IL-1␤, MIP-2, and IL-6 also were significantly upregulated, whereas the Th2 cytokines IL-4 (mRNA), IL-5 (mRNA), and IL-10 (mRNA and protein) were significantly reduced. CONCLUSIONS. ST2 is critical in resistance to P. aeruginosa keratitis, functioning to reduce corneal infection (bacterial load) and inflammation by negatively regulating proinflammatory cytokines and inhibiting type-1 immunity, but upregulating type-2 cytokine production, particularly IL-10. (Invest Ophthalmol Vis Sci.

Temporal-Spatial analysis of the immune response in a murine model of ovalbumin-induced airways inflammation

by B U Gajewska, F K Swirski, D Alvarez, S A Ritz, S Goncharova, M Cundall, D P Snider, A J Coyle, J C Gutierrez-Ramos, M R Stampfli, M Jordana - Am. J. Respir. Cell Mol. Biol , 2001
"... ..."
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IL-33 and Airway Inflammation

by Keisuke Oboki, Susumu Nakae, Kenji Matsumoto, Hirohisa Saito
"... as an alarmin that is released upon endothelial or epithelial cell damage and may not enhance acquired immune responses through activation of inflammasome. ST2, a IL-33 receptor component, is preferentially expressed by T-helper type (Th) 2 cells, mast cells, eosinophils and basophils, compared to T ..."
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as an alarmin that is released upon endothelial or epithelial cell damage and may not enhance acquired immune responses through activation of inflammasome. ST2, a IL-33 receptor component, is preferentially expressed by T-helper type (Th) 2 cells, mast cells, eosinophils and basophils, compared to Th1 cells, Th17 cells and neutrophils. Thus, IL-33 profoundly enhances allergic inflammation through increased expression of proallergic cytokines and chemokines. Indeed, IL-33 and its receptor genes are recognized as the most susceptible genes for asthma by several recent genomewide association studies. It has also recently been shown that IL-33 plays a crucial role in innate eosinophilic airway inflammation rather than acquired immune responses such as IgE production. As such, IL-33 provides a unique therapeutic way for asthma, i.e., ameliorating innate airway inflammation. Key Words: IL-33; ST2; host defense; allergy; autoimmunity; chronic disease; mast cell; basophil; eosinophil

signal

by Andrew Bowie, Luke A. J
"... The interleukin-1 receptor/Toll-like receptor superfamily: ..."
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The interleukin-1 receptor/Toll-like receptor superfamily:
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本文24-3

by めてお
"... Objective: A cytokine of the IL-1 family, IL-33, has recently been recognized as one of the key cytokines enhancing Th2-balanced immune regulation through its receptor, ST2. However, the action of IL-33 on allergic effector granulocytes has remained unclear. We thus tested whether IL-33 acts direct ..."
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Objective: A cytokine of the IL-1 family, IL-33, has recently been recognized as one of the key cytokines enhancing Th2-balanced immune regulation through its receptor, ST2. However, the action of IL-33 on allergic effector granulocytes has remained unclear. We thus tested whether IL-33 acts directly on, and affects the functions of, human basophils and eosinophils. Methods: Basophils and eosinophils were prepared from normal human peripheral blood. Cells were treated with IL-33, and their adhesion, migration, surface CD11b expression, mediator release and survival were assessed . Expression of ST2 was analyzed at both the mRNA and protein levels. Results: Analysis by real-time PCR and flow cytometry demonstrated that both basophils and eosinophils expressed mRNA and protein for ST2. Expressions of IL-4 and IL-13 mRNA in basophils were upregulated by IL-33. IL-33 at 1-100 ng/ml potently enhanced the adhesiveness and CD11b expression of basophils and eosinophils. Although IL-33 failed to directly induce degranulation or migration of basophils, it exerted priming effects by enhancing basophil migration toward eotaxin and degranulation in response to IgE-crosslinking stimulus. IL-33 prolonged survival of eosinophils, but not basophils, via suppression of their apoptosis. In addition, blocking of ST2 with neutralizing antibody inhibited IL-33-induced upregulation of basophil and eosinophil functions. Conclusion: IL-33 is a potent regulator of various functions of basophils and eosinophils. IL-33 may be a key cytokine in the pathogenesis of Th2-dominant allergic diseases, at least partly by acting on effector cells,

Paracrine IL-33 Stimulation Enhances Lipopolysaccharide-Mediated Macrophage Activation

by Tatsukuni Ohno, Keisuke Oboki, Hideaki Morita, Naoki Kajiwara, Ken Arae, Shizuko Tanaka, Miyuki Azuma, Ko Okumura, Thomas Kamradt, Hirohisa Saito, Susumu Nakae
"... Background: IL-33, a member of the IL-1 family of cytokines, provokes Th2-type inflammation accompanied by accumulation of eosinophils through IL-33R, which consists of ST2 and IL-1RAcP. We previously demonstrated that macrophages produce IL-33 in response to LPS. Some immune responses were shown to ..."
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Background: IL-33, a member of the IL-1 family of cytokines, provokes Th2-type inflammation accompanied by accumulation of eosinophils through IL-33R, which consists of ST2 and IL-1RAcP. We previously demonstrated that macrophages produce IL-33 in response to LPS. Some immune responses were shown to differ between ST2-deficient mice and soluble ST2-Fc fusion protein-treated mice. Even in anti-ST2 antibody (Ab)-treated mice, the phenotypes differed between distinct Ab clones, because the characterization of such Abs (i.e., depletion, agonistic or blocking Abs) was unclear in some cases. Methodology/Principal Findings: To elucidate the precise role of IL-33, we newly generated neutralizing monoclonal Abs for IL-33. Exogenous IL-33 potentiated LPS-mediated cytokine production by macrophages. That LPS-mediated cytokine production by macrophages was suppressed by inhibition of endogenous IL-33 by the anti-IL-33 neutralizing mAbs. Conclusions/Significance: Our findings suggest that LPS-mediated macrophage activation is accelerated by macrophage-
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Regulation of the IgE response

by Daniel H Conrad, David R Gibb, Jamie Sturgill , 2010
"... This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ..."
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This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial License
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Recombinant ST2 boosts hepatic Th2 response in vivo

by Aldo Amatucci, Tatiana Novobrantseva, Kevin Gilbride, Margot Brickelmaier, Paula Hochman, Alexander Ibraghimov , 2007
"... Abstract: Excessive scarring or fibrosis is a common feature of a wide spectrum of diseases characterized by an exaggerated Th2 response. The TLR/IL-1 receptor (IL-1R)-related protein ST2 is expressed in a membrane-bound form selectively by Th2 cells and was shown to be indispensable for some in viv ..."
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Abstract: Excessive scarring or fibrosis is a common feature of a wide spectrum of diseases characterized by an exaggerated Th2 response. The TLR/IL-1 receptor (IL-1R)-related protein ST2 is expressed in a membrane-bound form selectively by Th2 cells and was shown to be indispensable for some in vivo Th2 responses. ST2 was also found to block TLR signaling. We addressed the impact of the ST2 pathway on fibrogenesis using a mouse model of hepatic injury and fibrosis induced by carbon tetrachloride (CCl4). We showed that cytokine production by intrahepatic lymphocytes from CCl4-injured liver is abrogated in the absence of TLR-4. Interfering with the ST2 pathway using an ST2-Fc fusion protein accelerated and enhanced hepatic fibrosis, paralleled by the increasing ex vivo secretion of Th2 cytokines IL-4,-5,-10, and-13 by intrahepatic lymphocytes of ST2-Fctreated, CCl4-gavaged mice. Absence of IL-4/13 signaling in IL-4R�-deficient mice obliterated this ST2-Fc effect on fibrogenesis. Moreover, depletion of CD4 � T cells abrogated ST2-Fc-enhanced Th2 cytokines and accelerated fibrosis. Thus, ST2-Fc caused overproduction of Th2 cytokines by intrahepatic CD4 � T cells, possibly by modifying TLR-4 signaling in injured liver. This ST2-Fc-driven Th2
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