Proviral integration site for Moloney murine leukemia virus 1, but not phosphatidylinositol-3 kinase, is essential in the antiapoptotic signaling cascade.

Slides:

Advertisements

Similar presentations

TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis Maya Zimmermann, PhD, Andrea Koreck, MD, Norbert.

Advertisements

Phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase regulate induction of Mcl-1 and survival in glucocorticoid-treated human neutrophils

Upregulation of miR-18a-5p contributes to epidermal necrolysis in severe drug eruptions Asako Ichihara, MD, PhD, Zhongzhi Wang, PhD, Masatoshi Jinnin,

Weiguo Chen, MD, PhD, Yasuhiro Tabata, MD, PhD, Aaron M

Akos Heinemann, MD, Gunter J. Sturm, MD, Martina Ofner, BSc, Eva M

A novel TNFR1-triggered apoptosis pathway mediated by class IA PI3Ks in neutrophils by Barbara Geering, Ursina Gurzeler, Elena Federzoni, Thomas Kaufmann,

Eosinophilic disorders

Constitutively activated phosphatidylinositol-3 kinase (PI-3K) is involved in the defect of apoptosis in B-CLL: association with protein kinase Cδ by Ingo.

Phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase regulate induction of Mcl-1 and survival in glucocorticoid-treated human neutrophils

CD4+ T cells in patients with chronic inflammatory rheumatic disorders show distinct levels of exhaustion Theresa Frenz, PhD, Elena Grabski, PhD, Daniela.

Angiogenic effects of stromal cell-derived factor-1 (SDF-1/CXCL12) variants in vitro and the in vivo expressions of CXCL12 variants and CXCR4 in human.

Ting-ting Zhang, MSc, Klaus Okkenhaug, PhD, Baher F

Bruton tyrosine kinase mediates TLR9-dependent human dendritic cell activation Vassilios Lougaris, MD, Manuela Baronio, PhD, Massimiliano Vitali, PhD,

Alefacept (lymphocyte function-associated molecule 3/IgG fusion protein) treatment for atopic eczema Dagmar Simon, MD, Jennifer Wittwer, MD, Ganna Kostylina,

Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome

Histamine H2 receptor stimulation upregulates TH2 chemokine CCL17 production in human M2a macrophages Susanne Mommert, PhD, Karl Gregor, MD, Kristine.

Role of IL-9 in the pathophysiology of allergic diseases

Deficient glucocorticoid induction of anti-inflammatory genes in nasal polyp fibroblasts of asthmatic patients with and without aspirin intolerance Laura.

Reduction of CRKL expression in patients with partial DiGeorge syndrome is associated with impairment of T-cell functions Mauro Giacomelli, PhD, Rajesh.

IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin Robert J. Salmond, PhD, Ananda S. Mirchandani,

A role for phosphoinositol 3–kinase δ in the impairment of glucocorticoid responsiveness in patients with chronic obstructive pulmonary disease John.

Granulocyte-macrophage colony-stimulating factor and IL-5 activate mitogen-activated protein kinase through Jak2 kinase and phosphatidylinositol 3-kinase.

Recurrent viral infections associated with a homozygous CORO1A mutation that disrupts oligomerization and cytoskeletal association Christina S. Yee,

IL-10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain— containing protein tyrosine phosphatase 1 Alison Taylor, PhD, Mübeccel.

Expression of functional leukotriene B4 receptors on human airway smooth muscle cells Satoko Watanabe, BS, Akira Yamasaki, MD, PhD, Kiyoshi Hashimoto,

Curcumin, a constituent of curry, suppresses IgE-mediated allergic response and mast cell activation at the level of Syk Jun Ho Lee, PhD, Jie Wan Kim,

CD19 controls Toll-like receptor 9 responses in human B cells

The anti-inflammatory effect of glucocorticoids is mediated by glucocorticoid-induced leucine zipper in epithelial cells Jane Eddleston, PhD, Jack Herschbach,

Histamine Contributes to Tissue Remodeling via Periostin Expression

IL-13 desensitizes β2-adrenergic receptors in human airway epithelial cells through a 15-lipoxygenase/G protein receptor kinase 2 mechanism Giusy D.

TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis Maya Zimmermann, PhD, Andrea Koreck, MD, Norbert.

Mechanisms of tissue inhibitor of metalloproteinase 1 augmentation by IL-13 on TGF- β1–stimulated primary human fibroblasts Xiuxia Zhou, PhD, Haizhen.

Miriam Wittmann, MD, Jana Zeitvogel, Dong Wang, MD, Thomas Werfel, MD

Kathleen R. Bartemes, BA, Gail M. Kephart, BS, Stephanie J

Posttranscriptional regulation of IL-13 in T cells: Role of the RNA-binding protein HuR Vincenzo Casolaro, MD, PhD, Xi Fang, MD, Brian Tancowny, MS, Jinshui.

Analysis of antiapoptosis activity of human GM-CSF receptor

Steroid resistance of airway type 2 innate lymphoid cells from patients with severe asthma: The role of thymic stromal lymphopoietin Sucai Liu, PhD,

IL-13 dampens human airway epithelial innate immunity through induction of IL-1 receptor–associated kinase M Qun Wu, MD, PhD, Di Jiang, BS, Sean Smith,

FcɛRI cross-linking and IL-3 protect human basophils from intrinsic apoptotic stress Lionel Rohner, MSc, Ramona Reinhart, PhD, Björn Hagmann, PhD, Andrea.

Regulated in development and DNA damage responses 1 (REDD1) links stress with IL- 1β–mediated familial Mediterranean fever attack through autophagy-driven.

Corticosteroid-resistant asthma is associated with classical antimicrobial activation of airway macrophages Elena Goleva, PhD, Pia J. Hauk, MD, Clifton.

IL-2–inducible T-cell kinase modulates TH2-mediated allergic airway inflammation by suppressing IFN-γ in naive CD4+ T cells Arun K. Kannan, MS, Nisebita.

T-box 21 transcription factor is responsible for distorted TH2 differentiation in human peripheral CD4+ T cells Osamu Kaminuma, DVM, PhD, Fujiko Kitamura,

Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma Fei Huang, PhD, Shinichiro Wachi, PhD,

Targeting allergen to FcγRI reveals a novel TH2 regulatory pathway linked to thymic stromal lymphopoietin receptor Kathryn E. Hulse, PhD, Amanda J. Reefer,

Loss of syk kinase during IgE-mediated stimulation of human basophils

Patients with atopic dermatitis and history of eczema herpeticum elicit herpes simplex virus–specific type 2 immune responses Stephan Traidl, Petra Kienlin,

Activin A is an acute allergen-responsive cytokine and provides a link to TGF-β– mediated airway remodeling in asthma Christian Karagiannidis, MD, Gabriele.

Antiviral activity of human β-defensin 3 against vaccinia virus

Upregulation of Tenascin-C Expression by IL-13 in Human Dermal Fibroblasts via the Phosphoinositide 3-kinase/Akt and the Protein Kinase C Signaling Pathways

IL-17 in atopic eczema: Linking allergen-specific adaptive and microbial-triggered innate immune response Kilian Eyerich, MD, Davide Pennino, PhD, Claudia.

IκB kinase–driven nuclear factor-κB activation in patients with asthma and chronic obstructive pulmonary disease Rosalia Gagliardo, PhD, Pascal Chanez,

Staphylococcal exotoxins are strong inducers of IL-22: A potential role in atopic dermatitis Margarete Niebuhr, MD, Helena Scharonow, MS, Merle Gathmann,

Connective tissue growth factor expression is regulated by histamine in lung fibroblasts: Potential role of histamine in airway remodeling Steffen Kunzmann,

Increased activation-induced cell death of high IFN-γ–producing TH1 cells as a mechanism of TH2 predominance in atopic diseases Tunc Akkoc, PhD, Pieter.

IL-13 dampens human airway epithelial innate immunity through induction of IL-1 receptor–associated kinase M Qun Wu, MD, PhD, Di Jiang, BS, Sean Smith,

P38 Mitogen-activated protein kinase–induced glucocorticoid receptor phosphorylation reduces its activity: Role in steroid-insensitive asthma Elvis Irusen,

Matthew J. Loza, PhD, Susan Foster, PhD, Stephen P

Adhesion-induced eosinophil cytolysis requires the receptor-interacting protein kinase 3 (RIPK3)–mixed lineage kinase-like (MLKL) signaling pathway, which.

Rebound eosinophilia after treatment of hypereosinophilic syndrome and eosinophilic gastroenteritis with monoclonal anti–IL-5 antibody SCH55700 Yae-Jean.

Jenny Seltmann, PhD, Lennart M

CCL17/thymus and activation-regulated chemokine induces calcitonin gene–related peptide in human airway epithelial cells through CCR4 Kandace Bonner,

Eosinophil and neutrophil extracellular DNA traps in human allergic asthmatic airways Ryszard Dworski, MD, PhD, Hans-Uwe Simon, MD, PhD, Aimee Hoskins,

Systemic and localized seminal plasma hypersensitivity patients exhibit divergent immunologic characteristics Debajyoti Ghosh, PhD, Jonathan A. Bernstein,

IL-31 is associated with cutaneous lymphocyte antigen–positive skin homing T cells in patients with atopic dermatitis Janine Bilsborough, PhD, Donald.

Transforming growth factor β1 increases fibronectin deposition through integrin receptor α5β1 on human airway smooth muscle Lyn M. Moir, PhD, Janette.

Natural history of cow’s milk allergy

CCL17/thymus and activation-regulated chemokine induces calcitonin gene–related peptide in human airway epithelial cells through CCR4 Kandace Bonner,

Elevated serum osteopontin level is associated with blood eosinophilia and asthma comorbidity in patients with allergic rhinitis Wenlong Liu, MD, Wentong.

IL-2–inducible T-cell kinase modulates TH2-mediated allergic airway inflammation by suppressing IFN-γ in naive CD4+ T cells Arun K. Kannan, MS, Nisebita.

Presentation transcript:

Proviral integration site for Moloney murine leukemia virus 1, but not phosphatidylinositol-3 kinase, is essential in the antiapoptotic signaling cascade initiated by IL-5 in eosinophils Nicola Andina, MD, Svetlana Didichenko, PhD, Jan Schmidt-Mende, MD, PhD, Clemens A. Dahinden, MD, Hans-Uwe Simon, MD, PhD Journal of Allergy and Clinical Immunology Volume 123, Issue 3, Pages 603-611 (March 2009) DOI: 10.1016/j.jaci.2008.12.004 Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Pharmacologic inhibition of PI3K does not abrogate IL-5–mediated eosinophil survival. A, Immunoblotting. The 3 inhibitors LY294002, wortmannin, and IC87114 blocked IL-5–induced phosphorylation of both Akt and GSK3α/β. The immunoblots are representative of 3 independent experiments. GAPDH, Glyceraldehyde-3-phosphate dehydrogenase. B, Viability assay. LY294002, but not wortmannin and IC87114, abrogated IL-5–mediated eosinophil survival. Blood eosinophils were analyzed after 48-hour cultures. Similar results were observed when cells were analyzed after 24-hour cultures. Values are presented as means ± SDs (n = 4). ∗∗∗P < .001. Journal of Allergy and Clinical Immunology 2009 123, 603-611DOI: (10.1016/j.jaci.2008.12.004) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 IL-5 induces rapid Pim-1 expression in eosinophils in a Jak2-dependent but PI3K-independent manner. A, Immunoblotting. Pim-1 protein was expressed within 1 hour on IL-5 stimulation. B, Immunoblotting. IL-5–induced Pim-1 expression was not blocked by pharmacologic inhibition of PI3K. C, Immunoblotting. IL-5–induced Pim-1 expression was blocked by pharmacologic inhibition of Jak2 with both AG-490 (upper panel) and SD-1029 (lower panel). The duration of IL-5 stimulation is indicated in each panel. All immunoblots are representative of at least 3 independent experiments. GAPDH, Glyceraldehyde-3-phosphate dehydrogenase. Journal of Allergy and Clinical Immunology 2009 123, 603-611DOI: (10.1016/j.jaci.2008.12.004) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 IL-5–mediated eosinophil survival is Jak2 dependent. A, Viability assay. AG-490 inhibited, in a concentration-dependent manner, the survival effect of IL-5. Blood eosinophils were analyzed after 48-hour cultures. Similar results were observed when cells were analyzed after 24-hour cultures. B, Viability assay. SD-1029 inhibited, in a concentration-dependent manner, the survival effect of IL-5. Blood eosinophils were analyzed after 24-hour cultures and therefore control survival rates are higher compared with those seen in Fig 3, A. Similar results were observed when cells were analyzed after 48-hour cultures. Values are presented as means ± SDs of 4 (Fig 3, A) and 5 (Fig 3, B) independent experiments, respectively. ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001. Journal of Allergy and Clinical Immunology 2009 123, 603-611DOI: (10.1016/j.jaci.2008.12.004) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Pim-1 is required for IL-5–mediated eosinophil survival. A, Viability assay. Transduction of WT Pim-1 fusion protein alone resulted in increased eosinophil survival. The fusion protein was added at the indicated times. Its uptake and degradation was assessed by means of immunoblotting. Representative experiments are shown. B, Viability assay. In contrast to WT Pim-1, DN Pim-1 completely abrogated IL-5–mediated eosinophil survival. C, Phosphatidylserine redistribution assay. Transduction of WT Pim-1 resulted in reduced eosinophil apoptosis. DN Pim-1 blocked the antiapoptotic effect of IL-5. D, DNA fragmentation assay. Transduction of WT Pim-1 alone resulted in reduced eosinophil apoptosis. DN Pim-1 blocked the antiapoptotic effect of IL-5. The assays in all panels were performed after 24-hour cultures in which PMB was present. Values in Fig 4, B, C, and D, are presented as means ± SDs (n = 6). ∗∗P < .01 and ∗∗∗P < .001. Journal of Allergy and Clinical Immunology 2009 123, 603-611DOI: (10.1016/j.jaci.2008.12.004) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 IL-5 maintains Mcl-1 expression levels in a Pim-1–dependent manner in eosinophils. For immunoblotting, IL-5 stimulation resulted in stable Mcl-1 expression. Transduction of WT Pim-1 alone resulted in the same Mcl-1 expression levels. DN Pim-1 abolished the stabilizing effect of IL-5 on Mcl-1 levels. The immunoblots are representative of at least 3 independent experiments. GAPDH, Glyceraldehyde-3-phosphate dehydrogenase. Journal of Allergy and Clinical Immunology 2009 123, 603-611DOI: (10.1016/j.jaci.2008.12.004) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Pim-1 is expressed by eosinophils under inflammatory conditions in vivo. A and B, Immunofluorescence. Pim-1 was readily detected in infiltrating tissue eosinophils. Tissues were obtained from patients as indicated. Eosinophils were identified by using anti-ECP antibody. Control antibodies showed no staining (data not shown). C and D, Immunofluorescence. Pim-1 was not detectable in freshly isolated blood eosinophils from healthy individuals. In contrast, blood eosinophils demonstrated evidence for Pim-1 expression after 10 hours of in vitro stimulation with IL-5. Results in all panels are representative of at least 3 independent experiments (×1,000). Journal of Allergy and Clinical Immunology 2009 123, 603-611DOI: (10.1016/j.jaci.2008.12.004) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 7 Pim-1 is expressed by blood eosinophils from a subgroup of eosinophilic patients who exhibit reduced antiapoptotic responses after IL-5 stimulation. A, Immunoblotting. Freshly isolated blood eosinophils from healthy control individuals (Normal) and from patients with hypereosinophilic syndrome (HES), atopic eczema (AE), and atopic rhinitis (AR) were analyzed for Pim-1 expression. Blood eosinophil numbers from each patient/control individual are indicated. GAPDH, Glyceraldehyde-3-phosphate dehydrogenase. B, Viability assay. Based on the Pim-1 expression levels, as shown in Fig 7, A, donors were grouped as expressing high levels of Pim-1 (Pim-1 positive; hypereosinophilic syndrome no. 3, hypereosinophilic syndrome no. 5, atopic eczema no. 3, and atopic rhinitis no. 1) or low levels of Pim-1 (Pim-1 negative; remaining donors) and plotted against the IL-5–mediated effect on eosinophil viability (viability difference between the presence and absence of IL-5 in 24-hour eosinophil cultures). ∗∗P < .01. Journal of Allergy and Clinical Immunology 2009 123, 603-611DOI: (10.1016/j.jaci.2008.12.004) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions