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

Slides:

Advertisements

Similar presentations

Proinflammatory cytokine–induced and chemical mediator–induced IL-8 expression in human bronchial epithelial cells through p38 mitogen-activated protein.

Advertisements

Differential effects of GLP-1 receptor agonist on foam cell formation in monocytes between non-obese and obese subjects Masashi Tanaka, Yoshiyuki Matsuo,

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

In Cardiomyocyte Hypoxia, Insulin-Like Growth Factor-I-Induced Antiapoptotic Signaling Requires Phosphatidylinositol-3-OH-Kinase-Dependent and Mitogen-Activated.

Cell-specific activation profile of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic.

Thymic stromal lymphopoietin downregulates filaggrin expression by signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated.

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

Regulation of GM-CSF expression by the transcription factor c-Maf

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

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

IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis Norbert Meyer, MD, Maya Zimmermann, PhD,

Volume 120, Issue 7, Pages (June 2001)

Julie M. Caldwell, PhD, Carine Blanchard, PhD, Margaret H

Pentraxin 3 deletion aggravates allergic inflammation through a TH17-dominant phenotype and enhanced CD4 T-cell survival Jyoti Balhara, MSc, Lianyu Shan,

Role of IL-9 in the pathophysiology of allergic diseases

CD40-mediated p38 mitogen-activated protein kinase activation is required for immunoglobulin class switch recombination to IgE Ke Zhang, MD, PhD, Ling.

Glenn Cruse, PhD, Shailendra R. Singh, PhD, S

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.

H.T. Lee, M. Kim, M. Jan, R.B. Penn, C.W. Emala Kidney International

Cell-specific activation profile of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic.

Inhibition of differentiation, amplification, and function of human TH17 cells by intravenous immunoglobulin Mohan S. Maddur, DVM, Janakiraman Vani,

Enhancement of depsipeptide-mediated apoptosis of lung or esophageal cancer cells by flavopiridol: Activation of the mitochondria-dependent death-signaling.

John F. Öhd, Katarina Wikström, Anita Sjölander Gastroenterology

AKT Delays the Early-Activated Apoptotic Pathway in UVB-Irradiated Keratinocytes Via BAD Translocation Sofie Claerhout, David Decraene, An Van Laethem,

Indomethacin Sensitizes TRAIL-Resistant Melanoma Cells to TRAIL-Induced Apoptosis through ROS-Mediated Upregulation of Death Receptor 5 and Downregulation.

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

Cysteinyl leukotriene E4 activates human group 2 innate lymphoid cells and enhances the effect of prostaglandin D2 and epithelial cytokines Maryam Salimi,

Volume 136, Issue 4, Pages e3 (April 2009)

Toll-like receptor 9 suppression in plasmacytoid dendritic cells after IgE-dependent activation is mediated by autocrine TNF-α John T. Schroeder, PhD,

The innate antiviral response upregulates IL-13 receptor α2 in bronchial fibroblasts Gemma Campbell-Harding, PhD, Hannah Sawkins, BSc, Nicole Bedke, PhD,

Toluene downregulates filaggrin expression via the extracellular signal-regulated kinase and signal transducer and activator of transcription–dependent.

Corticosteroid insensitivity of chemokine expression in airway smooth muscle of patients with severe asthma Po-Jui Chang, MD, Pankaj K. Bhavsar, PhD,

AT-101, a Pan-Bcl-2 Inhibitor, Leads to Radiosensitization of Non-small Cell Lung Cancer Luigi Moretti, MD, Bo Li, MD, Kwang Woon Kim, PhD, Heidi Chen,

Analysis of antiapoptosis activity of human GM-CSF receptor

Lovastatin Sensitizes Lung Cancer Cells to Ionizing Radiation: Modulation of Molecular Pathways of Radioresistance and Tumor Suppression Toran Sanli,

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.

Glucocorticoids inhibit IL-4 and mitogen-induced IL-4Rα chain expression by different posttranscriptional mechanisms Lourdes Mozo, PhDa, Abel Gayo, BSa,

All-Trans-Retinoic Acid Induces Interleukin-8 via the Nuclear Factor-κB and p38 Mitogen-Activated Protein Kinase Pathways in Normal Human Keratinocytes

Volume 128, Issue 7, Pages (June 2005)

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

PPARδ Is a Type 1 IFN Target Gene and Inhibits Apoptosis in T Cells

Roflumilast N-oxide reverses corticosteroid resistance in neutrophils from patients with chronic obstructive pulmonary disease Javier Milara, PhD, PharmD,

Prostaglandin D2 and leukotriene E4 synergize to stimulate diverse TH2 functions and TH2 cell/neutrophil crosstalk Luzheng Xue, PhD, Joannah Fergusson,

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

Mechanism of Siglec-8–mediated cell death in IL-5–activated eosinophils: Role for reactive oxygen species–enhanced MEK/ERK activation Gen Kano, MD, PhD,

Volume 61, Issue 2, Pages (February 2002)

IL-17E upregulates the expression of proinflammatory cytokines in lung fibroblasts Séverine Létuvé, PhD, Stéphane Lajoie-Kadoch, MSc, Séverine Audusseau,

Amplification of Toll-like receptor–mediated signaling through spleen tyrosine kinase in human B-cell activation Shigeru Iwata, MD, PhD, Kunihiro Yamaoka,

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,

MicroRNA-4443 regulates mast cell activation by T cell–derived microvesicles Irit Shefler, PhD, Pazit Salamon, PhD, Francesca Levi-Schaffer, PharmD, Adam.

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

Toll-like receptor 2 ligands activate human basophils for both IgE-dependent and IgE- independent secretion Anja P. Bieneman, BS, Kristin L. Chichester,

Dysregulation of innate immune receptors on neutrophils in chronic granulomatous disease Dominik Hartl, MD, Natalie Lehmann, MD, Florian Hoffmann, MD,

D-type prostanoid receptor enhances the signaling of chemoattractant receptor– homologous molecule expressed on TH2 cells Miriam Sedej, MSc, Ralf Schröder,

Synergistic effects of fluticasone propionate and salmeterol on in vitro T-cell activation and apoptosis in asthma Elisabetta Pace, MD, Rosalia Gagliardo,

Leukotriene D4 induces gene expression in human monocytes through cysteinyl leukotriene type I receptor Grzegorz Woszczek, MD, PhD, Li-Yuan Chen, PhD,

IgE induces transcriptional regulation of thymic stromal lymphopoietin in human airway smooth muscle cells Naresh Singh Redhu, MSc, Ali Saleh, PhD, Hai-Chon.

Mechanism of TH2/TH17-predominant and neutrophilic TH2/TH17-low subtypes of asthma Weimin Liu, PhD, Sucai Liu, PhD, Mukesh Verma, PhD, Iram Zafar, MS,

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

Toll-like receptor agonists differentially regulate cysteinyl-leukotriene receptor 1 expression and function in human dendritic cells Maryse Thivierge,

Regulation of IL-13 receptor α1 expression and signaling on human tonsillar B- lymphocyte subsets Oumnia Hajoui, PhD, Huaien Zheng, MD, PhD, Julie Guay,

Zhenying Nie, PhD, Cole S. Nelson, PhD, David B. Jacoby, MD, Allison D

Volume 61, Issue 2, Pages (February 2002)

Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma

Hydroxychloroquine preferentially induces apoptosis of CD45RO+ effector T cells by inhibiting autophagy: A possible mechanism for therapeutic modulation.

Mechanism of TH2/TH17-predominant and neutrophilic TH2/TH17-low subtypes of asthma Weimin Liu, PhD, Sucai Liu, PhD, Mukesh Verma, PhD, Iram Zafar, MS,

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

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

Presentation transcript:

Phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase regulate induction of Mcl-1 and survival in glucocorticoid-treated human neutrophils Arash S. Saffar, DDS, Stéphane Dragon, BSc, Peyman Ezzati, BSc, Lianyu Shan, MSc, Abdelilah Soussi Gounni, PhD Journal of Allergy and Clinical Immunology Volume 121, Issue 2, Pages 492-498.e10 (February 2008) DOI: 10.1016/j.jaci.2007.10.003 Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Dexamethasone upregulated antiapoptotic Mcl-1. Freshly isolated neutrophils (time 0) and those cultured for various time points were analyzed for Mcl-1 by means of immunoblotting and densitometry (A and B) or real-time RT-PCR (C). ∗P < .05; ∗∗P < .01 (n = 6). Dex, Dexamethasone; RU, RU-486; MG, MG-132; Med, medium. Journal of Allergy and Clinical Immunology 2008 121, 492-498.e10DOI: (10.1016/j.jaci.2007.10.003) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Inhibition of PI3K and p38 MAPK suppressed glucocorticoid-mediated survival of neutrophils. Freshly isolated human neutrophils were preincubated with 25 nmol/L wortmannin (A), 5 μmol/L U0126 (B), 10 μmol/L SP600125 (C), 25 μmol/L SB203580 (D), or dimethyl sulfoxide before stimulation with dexamethasone (Dex), GM-CSF, or medium alone. Apoptosis was assessed by using annexin-V/propidium iodide staining. ∗∗∗P < .0005; ∗∗P < .005 (n = 8-9). Journal of Allergy and Clinical Immunology 2008 121, 492-498.e10DOI: (10.1016/j.jaci.2007.10.003) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 PI3K and p38 MAPK regulated the induction of survival and Mcl-1 by dexamethasone. Neutrophils were assessed for apoptosis by using annexin-V/propidium iodide staining (A and B; 1 μmol/L U0126, 10 μmol/L SB203580, or 10 nmol/L wortmannin), immunoblotted for Mcl-1 (C; 25 μmol/L SB203580 or 25 nmol/L wortmannin), and analyzed after 18 hours for mitochondrial potential or after 6 hours for caspase-3 activity (D and E; 25 μmol/L SB203580, 25 nmol/L wortmannin, or 10 μmol/L SB203580 plus 10 nmol/L wortmannin). ∗∗∗P < .001; ∗∗P < .01; ∗P < .05. SB, SB203580; Dex, dexamethasone; Wort, wortmannin; RU, RU-486. Journal of Allergy and Clinical Immunology 2008 121, 492-498.e10DOI: (10.1016/j.jaci.2007.10.003) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Dexamethasone delayed apoptosis of neutrophils Dexamethasone delayed apoptosis of neutrophils. A, Freshly isolated human neutrophils were cultured and assessed for apoptosis by means of annexin-V/propidium iodide staining (∗∗∗P < .0001 and ∗∗P < .005 compared with medium; n = 8). B, Freshly isolated human neutrophils were cultured for 24 hours and assessed for apoptosis by using a DNA fragmentation assay (∗∗∗P < .0005 and ∗∗P < .01 compared with medium; n = 5). Dex, Dexamethasone; RU, RU-486; CHX, 10 ng/mL cycloheximide. Journal of Allergy and Clinical Immunology 2008 121, 492-498.e10DOI: (10.1016/j.jaci.2007.10.003) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Glucocorticoids induced neutrophil survival independently of transrepression. Freshly isolated human neutrophils were cultured with various concentrations of CpdA and assessed for apoptosis by using either annexin-V/propidium iodide staining (A; ∗∗∗P < .0001 compared with medium; n = 4) or DNA fragmentation assay (B; 24-hour culture; ∗∗P < .005 compared with medium; n = 3). C, Expression of Fas was analyzed by means of FACS in neutrophils cultured for 18 hours. The shaded line represents the isotype control. The average of mean fluorescence intensity (MFI) was calculated from 3 independent experiments. D, Freshly isolated neutrophils (time 0) and those cultured for 6 and 12 hours were lysed and analyzed for total levels of Bax and Bid by means of immunoblotting. D represents 3 separate experiments. Dex, Dexamethasone; RU, RU-486. Journal of Allergy and Clinical Immunology 2008 121, 492-498.e10DOI: (10.1016/j.jaci.2007.10.003) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Dexamethasone upregulated antiapoptotic XIAP protein Dexamethasone upregulated antiapoptotic XIAP protein. IAPs were detected in total lysates of fresh neutrophils or neutrophils cultured for 6 and 12 hours by means of Western blotting and quantified by means of densitometry. Densitometric results are reported as fold increase over average value for time 0. The figure represents 3 independent experiments (∗P < .05; ∗∗P < .01). Dex, Dexamethasone; RU, RU-486; XIAP, X-chromosome linked inhibitor of apoptosis protein; cIAP, cellular inhibitor of apoptosis protein. Journal of Allergy and Clinical Immunology 2008 121, 492-498.e10DOI: (10.1016/j.jaci.2007.10.003) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Dexamethasone suppressed proapoptotic activity at the level of mitochondria. Western blotting was performed on subcellular fractions of freshly isolated neutrophils (time 0) or those cultured for 18 hours. Manganese superoxide dismutase (MnSOD) and GAPDH served as mitochondrial and cytosolic content controls, respectively. Panels represent 3 separate experiments. Dex, Dexamethasone; RU, RU-486. Journal of Allergy and Clinical Immunology 2008 121, 492-498.e10DOI: (10.1016/j.jaci.2007.10.003) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Caspase activity in neutrophils was suppressed by dexamethasone Caspase activity in neutrophils was suppressed by dexamethasone. Enzymatic activity of caspase-8 and caspase-9 (A) and caspase-3 (B) was measured in neutrophils cultured for various time points. Data are reported as fold increase over average value for GM-CSF. Anti-Fas IgM (250 ng/mL) served as a positive control (∗P < .05; ∗∗∗P < .001; n = 5, performed in triplicate). C, Western blots were performed for active caspase-3 and its zymogen (procaspase-3) on lysates from fresh neutrophils (time 0) or those cultured for 12 and 18 hours. C represents 3 separate experiments. Dex, Dexamethasone; RU, RU-486. Journal of Allergy and Clinical Immunology 2008 121, 492-498.e10DOI: (10.1016/j.jaci.2007.10.003) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Inhibition of PI3K blocked dexamethasone-induced survival of neutrophils without causing necrosis. Freshly isolated human neutrophils were preincubated with 25 nmol/L wortmannin or dimethyl sulfoxide before stimulation with dexamethasone or medium alone. Representative FACS plots of annexin-V/propidium iodide staining patterns of neutrophils are shown. Dex, Dexamethasone. Journal of Allergy and Clinical Immunology 2008 121, 492-498.e10DOI: (10.1016/j.jaci.2007.10.003) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Akt and p38 MAPK were activated after dexamethasone stimulation of neutrophils. Freshly isolated human neutrophils were preincubated with 25 nmol/L wortmannin (A), 25 μmol/L SB203580 (B), or dimethyl sulfoxide before stimulation with dexamethasone or medium alone. These cells were collected and lysed at the specified time points, followed by immunoblotting for total and phosphorylated Akt (Fig E7, A) or p38 MAPK (Fig E7, B). The figure is representative of 5 separate experiments. Dex, Dexamethasone. Journal of Allergy and Clinical Immunology 2008 121, 492-498.e10DOI: (10.1016/j.jaci.2007.10.003) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Glucocorticoid-induced survival of human neutrophils: a schematic model. After treatment of neutrophils with dexamethasone, dimerization and movement of the glucocorticoid receptor to the nucleus is thought to occur. Within hours, Mcl-1 and IAPs are upregulated, correlating with maintenance of mitochondrial integrity and suppression of caspases. PI3K and p38 MAPK regulate this process at or upstream of mitochondria. Journal of Allergy and Clinical Immunology 2008 121, 492-498.e10DOI: (10.1016/j.jaci.2007.10.003) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions