Signal transducer and activator of transcription 1 decoy oligodeoxynucleotide suppression of contact hypersensitivity Andreas H. Wagner, PhD, Inka Wittjen,

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

Toll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4–mediated suppression of IL-10 Susanne Kaesler, PhD, Thomas Volz, MD, Yuliya.

Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of TH17 cells and their ex vivo expansion

MicroRNA-146a suppresses IL-17–mediated skin inflammation and is genetically associated with psoriasis Ankit Srivastava, MTech, Pernilla Nikamo, PhD,

Natalija Novak, MD Journal of Allergy and Clinical Immunology

Russell S. Traister, MD, PhD, Crystal E. Uvalle, BS, Gregory A

CD39: A new surface marker of mouse regulatory γδ T cells

Laurent L'homme, PhD, David Dombrowicz, PhD

Modulation by aspirin of nuclear phospho–signal transducer and activator of transcription 6 expression: Possible role in therapeutic benefit associated.

Umasundari Sivaprasad, PhD, David J. Askew, PhD, Mark B

Prostaglandin E2 suppresses CCL27 production through EP2 and EP3 receptors in human keratinocytes Naoko Kanda, MD, PhD, Hiroshi Mitsui, MD, PhD, Shinichi.

IL-10 disrupts the Brd4-docking sites to inhibit LPS-induced CXCL8 and TNF-α expression in monocytes: Implications for chronic obstructive pulmonary disease

Calcitonin gene-related peptide– and vascular endothelial growth factor–positive inflammatory cells in late-phase allergic skin reactions in atopic subjects

Nitric oxide inhibits human rhinovirus-induced transcriptional activation of CXCL10 in airway epithelial cells Rommy Koetzler, MD, MSc, Raza S. Zaheer,

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

Inflammatory marker analysis in psoriatic skin under topical phosphodiesterase 4 inhibitor treatment Lennart M. Roesner, PhD, Petra Kienlin, Gabriele.

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

Cytokine-inducible CD40 expression in human endothelial cells is mediated by interferon regulatory factor-1 by Andreas H. Wagner, Matthias Gebauer, Beatrix.

Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of TH17 cells and their ex vivo expansion

Defective killing of Staphylococcus aureus in atopic dermatitis is associated with reduced mobilization of human β-defensin-3 Kevin O. Kisich, PhD, Charles.

Leukocyte nicotinamide adenine dinucleotide phosphate-reduced oxidase is required for isocyanate-induced lung inflammation Si-Yen Liu, PhD, Wei-Zhi Wang,

Is 9 more than 2 also in allergic airway inflammation?

IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis James G. Krueger, MD, Scott Fretzin, MD, Mayte Suárez-Fariñas,

CpG-DNA enhances the tight junction integrity of the bronchial epithelial cell barrier Terufumi Kubo, MD, PhD, Paulina Wawrzyniak, MSc, Hideaki Morita,

Human IL-31 is induced by IL-4 and promotes TH2-driven inflammation

Aeroallergen-induced IL-33 predisposes to respiratory virus–induced asthma by dampening antiviral immunity Jason P. Lynch, PhD, Rhiannon B. Werder, B.

Signal transducer and activator of transcription 1 decoy oligodeoxynucleotide suppression of contact hypersensitivity Andreas H. Wagner, PhD, Inka Wittjen,

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

Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1–high T cells Jong Hoon.

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

Culture medium from TNF-α–stimulated mesenchymal stem cells attenuates allergic conjunctivitis through multiple antiallergic mechanisms Wenru Su, MD,

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

NF-κB and STAT3 Inhibition as a Therapeutic Strategy in Psoriasis: In Vitro and In Vivo Effects of BTH Rosa M. Andrés, M. Carmen Montesinos, Pedro Navalón,

Antagonistic effect of the inflammasome on thymic stromal lymphopoietin expression in the skin Sonia Schuepbach-Mallepell, PhD, Virginie Philippe, PhD,

Bronchial mucosal IFN-α/β and pattern recognition receptor expression in patients with experimental rhinovirus-induced asthma exacerbations Jie Zhu,

The Janus kinase inhibitor JTE-052 improves skin barrier function through suppressing signal transducer and activator of transcription 3 signaling Wataru.

The Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in the p38/TNF-α Pathway of Systemic and Cutaneous Inflammation Arndt J. Schottelius,

Peanut-induced intestinal allergy is mediated through a mast cell–IgE–FcεRI–IL-13 pathway Meiqin Wang, MD, PhD, Katsuyuki Takeda, MD, PhD, Yoshiki Shiraishi,

Toll-like receptor 2 is important for the TH1 response to cutaneous sensitization Haoli Jin, MD, PhD, Lalit Kumar, PhD, Clinton Mathias, PhD, David Zurakowski,

Sabine Leisten, MSc, Michiko K

Downregulation of a disintegrin and metalloproteinase 33 by IFN-γ in human airway smooth muscle cells Isao Ito, MD, PhD, Johanne D. Laporte, PhD, Pierre.

Time for a paradigm shift in asthma treatment: From relieving bronchospasm to controlling systemic inflammation Leif Bjermer, MD Journal of Allergy.

Receptor-interacting protein kinase 3 controls keratinocyte activation in a necroptosis- independent manner and promotes psoriatic dermatitis in mice

Baricitinib treatment in a patient with a gain-of-function mutation in signal transducer and activator of transcription 1 (STAT1) Kornvalee Meesilpavikkai,

Food allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management Scott H. Sicherer, MD, Hugh A. Sampson, MD Journal.

Engagement of CD47 Inhibits the Contact Hypersensitivity Response Via the Suppression of Motility and B7 Expression by Langerhans Cells Xijun Yu, Atsushi.

Lisa G. Wood, PhD, Manohar L. Garg, PhD, Peter G. Gibson, MBBS

Hirotake Suzuki, Binghe Wang, Gulnar M

Enhanced CD46-induced regulatory T cells suppress allergic inflammation after Dermatophagoides pteronyssinus–specific immunotherapy Yi-Giien Tsai, MD,

Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling Saeko Nakajima,

IL-17A Upregulates Keratin 17 Expression in Keratinocytes through STAT1- and STAT3- Dependent Mechanisms Xiaowei Shi, Liang Jin, Erle Dang, Ting Chang,

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

The Janus kinase inhibitor JTE-052 improves skin barrier function through suppressing signal transducer and activator of transcription 3 signaling Wataru.

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

Sara Paveglio, PhD, MS, Erin Bennett, MS, Kelly L. Hawley, PhD, Adam P

MicroRNA-146a suppresses IL-17–mediated skin inflammation and is genetically associated with psoriasis Ankit Srivastava, MTech, Pernilla Nikamo, PhD,

Topical application of dehydroxymethylepoxyquinomicin improves allergic inflammation via NF-κB inhibition Asuka Hamasaka, MD, PhD, Naoya Yoshioka, MS,

Improvement of treatment-refractory atopic dermatitis by immunoadsorption: A pilot study Michael Kasperkiewicz, MD, Enno Schmidt, MD, PhD, Yvonne Frambach,

Acute Pseudomonas challenge in cystic fibrosis mice causes prolonged nuclear factor- κB activation, cytokine secretion, and persistent lung inflammation

Toll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4–mediated suppression of IL-10 Susanne Kaesler, PhD, Thomas Volz, MD, Yuliya.

The steroidogenic enzyme Cyp11a1 is essential for development of peanut-induced intestinal anaphylaxis Meiqin Wang, MD, PhD, Julita Ramirez, DVM, PhD,

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

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

Prostaglandin E2–EP3 signaling suppresses skin inflammation in murine contact hypersensitivity Tetsuya Honda, MD, PhD, Toshiyuki Matsuoka, MD, PhD, Mayumi.

Julie Negri, BA, S. Brandon Early, BA, John W

Aeroallergen-induced IL-33 predisposes to respiratory virus–induced asthma by dampening antiviral immunity Jason P. Lynch, PhD, Rhiannon B. Werder, B.

Nrf2 activation by sulforaphane restores the age-related decrease of TH1 immunity: Role of dendritic cells Hyon-Jeen Kim, PhD, Berenice Barajas, BS,

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

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

TNF can contribute to multiple features of ovalbumin-induced allergic inflammation of the airways in mice Susumu Nakae, PhD, Carolina Lunderius, PhD,

Presentation transcript:

Signal transducer and activator of transcription 1 decoy oligodeoxynucleotide suppression of contact hypersensitivity Andreas H. Wagner, PhD, Inka Wittjen, MD, Tomislav Stojanovic, MD, Peter Middel, MD, Josef G. Meingassner, DVM, Markus Hecker, PhD Journal of Allergy and Clinical Immunology Volume 121, Issue 1, Pages 158-165.e5 (January 2008) DOI: 10.1016/j.jaci.2007.09.015 Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Detection of Texas Red–labeled STAT1 dODN penetration into guinea pig skin. A, Time-dependent uptake of the fluorescent dODN (0.2% ointment). B, Detection of the fluorescent dODN in the epidermis (1) and a hair follicle (2) 6 hours after topical application. The right panel shows 4′-6-diamidino-2-phenylindole dihydrochloride (DAPI)–stained nuclei. Scale bar, 100 μm. Journal of Allergy and Clinical Immunology 2008 121, 158-165.e5DOI: (10.1016/j.jaci.2007.09.015) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Topical STAT1 dODN treatment reduces the macroscopic (A) and histopathologic (B) signs of inflammation, as well as the increase in epidermal thickness (C), in the guinea pig CHS model 24 hours after challenge with DNCB. Statistical summary of the evaluation of 18 and 6 (clobetasol) test sites, respectively, is shown. ∗P < .05 versus DNCB plus vehicle; †P < .05 versus 0.13% STAT1 dODN. Journal of Allergy and Clinical Immunology 2008 121, 158-165.e5DOI: (10.1016/j.jaci.2007.09.015) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 STAT1 dODN attenuation of neutrophil (A), T-cell (B), and monocyte/macrophage (C) infiltration into the guinea pig skin 24 hours after DNCB challenge. Statistical summary of the mean cell count per unit area in 3 to 5 random fields of view of 18 and 6 (clobetasol) specimens, respectively, is shown. ∗P < .05 versus DNCB plus vehicle; †P < .05 versus 0.13% STAT1 dODN. Journal of Allergy and Clinical Immunology 2008 121, 158-165.e5DOI: (10.1016/j.jaci.2007.09.015) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 STAT1 dODN suppression of DNCB-induced mRNA expression of IL-1β (A), IL-8 (B), IFN-γ (C), IL-12p40 (D), and TNF-α (E) in the guinea pig skin 24 hours after challenge. Statistical summary of real-time PCR data obtained with 18 and 6 (clobetasol) biopsy specimens, respectively, is shown. ∗P < .05 versus DNCB plus vehicle and 0.13% control ODN; †P < .05 versus STAT1 dODN. Journal of Allergy and Clinical Immunology 2008 121, 158-165.e5DOI: (10.1016/j.jaci.2007.09.015) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 STAT1 dODN–mediated decrease in IL-8 and CD40 protein abundance in guinea pig skin biopsy specimens taken 24 hours after challenge with DNCB. Representative immunohistochemistry analyses are shown. Scale bar, 50 μm (IL-8) and 100 μm (CD40), respectively. Journal of Allergy and Clinical Immunology 2008 121, 158-165.e5DOI: (10.1016/j.jaci.2007.09.015) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Topical STAT1 dODN treatment diminishes the clinical signs of CHS in the domestic pig model (A) and edema formation in the mouse model (B). Statistical summary of the scoring of 6 to 12 test sites in the preventive treatment arm 24 hours after DNFB challenge is shown in Fig 6, A. ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001 versus vehicle. Statistical summary of the changes in ear weight (difference in milligrams between challenged and unchallenged ear) in 8 animals each 24 and 48 hours after challenge with FITC is shown in Fig 6, B. ∗P < .05 and ∗∗∗P < .001 versus vehicle. Journal of Allergy and Clinical Immunology 2008 121, 158-165.e5DOI: (10.1016/j.jaci.2007.09.015) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Activation of AP-1 and STAT1 in guinea pig skin biopsy specimens collected 24 hours after challenge with DNCB. Appropriate [γ-32P]adenosine triphosphate–labeled gel shift oligonucleotides were used for detection of either transcription factor in nuclear extracts of these specimens (representative EMSA). Journal of Allergy and Clinical Immunology 2008 121, 158-165.e5DOI: (10.1016/j.jaci.2007.09.015) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Exemplary results demonstrating the inhibitory effect of the topical STAT1 dODN formulation on the macroscopic (A) and histopathologic (B) signs of inflammation in the guinea pig model of contact hypersensitivity 24 hours after challenge with DNCB. In Fig E2, B, the comparable effect of 0.13% STAT1 dODN ointment and 0.25% clobetasol propionate on epidermal spongiosis and leukocyte infiltration is readily apparent. Journal of Allergy and Clinical Immunology 2008 121, 158-165.e5DOI: (10.1016/j.jaci.2007.09.015) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

STAT1 dODN–mediated reduction in neutrophil (A), T-cell (B), and monocyte/macrophage (C) infiltration into guinea pig skin 24 hours after DNCB challenge. Representative images are shown. Scale bar, 100 μm. Journal of Allergy and Clinical Immunology 2008 121, 158-165.e5DOI: (10.1016/j.jaci.2007.09.015) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Specificity of the STAT dODN in cultured PAECs Specificity of the STAT dODN in cultured PAECs. IFN-γ (1000 U/mL, 30 minutes)–induced nuclear translocation of STAT1 is significantly reduced in cells pretreated with the consensus (cons) STAT1 dODN (10 μmol/L, 4 hours) but not the corresponding scrambled (scr) control ODN. A sis-inducible element gel shift oligonucleotide was used for detection of STAT1 in the nuclear extracts. Correct assignment of the STAT1-containing DNA-protein complex was confirmed by means of gel shift supershift (SS) analysis with a specific IgG antibody. Journal of Allergy and Clinical Immunology 2008 121, 158-165.e5DOI: (10.1016/j.jaci.2007.09.015) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions