Presentation is loading. Please wait.

Presentation is loading. Please wait.

Salmeterol attenuates chemotactic responses in rhinovirus-induced exacerbation of allergic airways disease by modulating protein phosphatase 2A  Luke.

Published byBorgar Larsen Modified over 4 years ago

Similar presentations

Presentation on theme: "Salmeterol attenuates chemotactic responses in rhinovirus-induced exacerbation of allergic airways disease by modulating protein phosphatase 2A  Luke."— Presentation transcript:

1 Salmeterol attenuates chemotactic responses in rhinovirus-induced exacerbation of allergic airways disease by modulating protein phosphatase 2A  Luke Hatchwell, BBiomedSci (Hons), Jason Girkin, BBiomedSci (Hons), Matthew D. Dun, PhD, Matthew Morten, BBiomedSci (Hons), Nicole Verrills, PhD, Hamish D. Toop, BSci (Hons), Jonathan C. Morris, PhD, Sebastian L. Johnston, PhD, Paul S. Foster, PhD, DSc, Adam Collison, PhD, Joerg Mattes, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 133, Issue 6, Pages (June 2014) DOI: /j.jaci Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Salmeterol suppresses AHR and inflammation in AAD. A, Total lung resistance (RI) presented as raw baseline values and percentage change in response to methacholine (n = 8 mice per group). B, Cells in bronchoalveolar lavage (BAL) fluid. C, Tissue eosinophils per 100 μm2. D, Proportions of blood leukocytes. Results are presented as means ± SEMs (n = 3-6 mice per group). *P < .05 and **P < .01 compared with the vehicle control group. Eos, Eosinophils; Lym, lymphocytes; Mac, macrophages; Neu, neutrophils; SAL, sterile saline. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Salmeterol attenuates chemokine but not TH2 cytokine expression. A and B, Cytokine/chemokine expression in lower airway tissue (Fig 2, A and B) and protein levels of CXCL2 (Fig 2, B). C-E, PP2A activity (Fig 2, C), p-ERK1 (Fig 2, D), and activated NF-κB subunits (Fig 2, E) quantified from lung lysates by using ELISA. Results are presented as means ± SEMs (n = 3-6 mice per group). *P < .05, **P < .01, and ***P < .001 compared with the vehicle control group. SAL, Sterile saline. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Inhibition of PP2A reverses the therapeutic effect of salmeterol. A and B, PP2A activity and PP2Ac protein (Fig 3, A) and chemokines (Fig 3, B) in lung lysates. C, Cells in bronchoalveolar lavage (BAL) fluid. Eos, Eosinophils; Lym, lymphocytes; Mac, macrophages; Neu, neutrophils. D, Cytokine expression in lower airway tissue. Results are presented as means ± SEMs (n = 3-6 mice per group). *P < .05, **P < .01, and ***P < .001 compared with the vehicle control group or otherwise indicated. SAL, Sterile saline. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Salmeterol and dexamethasone suppress rhinovirus-induced exacerbation. A, Total lung resistance (RI) presented as raw baseline values and percentage change in response to methacholine (n = 6-9 mice per group). B, Tissue eosinophils per 100 μm2. C and D, Gene expression in lower airway tissue (Fig 4, C and D) and protein levels of CCL20 and CXCL2 (Fig 4, D). Results are presented as means ± SEMs (n = 3-6 mice per group). *P < .05 and **P < .01 compared with the vehicle control group. SAL, Sterile saline. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Salmeterol, but not dexamethasone, increases PP2A activity in vivo and in vitro. PP2A activity in lung lysates of rhinovirus-exacerbated mice (A), human BEAS-2B cells (B), or immunopurified PP2A complexes (C) after treatment with salmeterol, dexamethasone, or their combination is shown. Results are presented as means ± SEMs (n = 4-6 mice per group or 3 independent experiments). *P < .05, **P < .01, and ***P < .001 compared with the vehicle control group. SAL, Sterile saline. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 The PP2A agonist AAL(S) prevents rhinovirus-induced exacerbation. A and B, PP2A activity (Fig 6, A) and total lung resistance (RI; Fig 6, B) are presented as raw baseline values and percentage change in response to methacholine (n = 4-6 mice per group). C and D, Tissue eosinophils per 100 μm2 (Fig 6, C) and gene and protein expression of chemokines (Fig 6, D). Results are presented as means ± SEMs (n = 3-5 mice per group). *P < .05 and ***P < .001 compared with the vehicle control group. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Download ppt "Salmeterol attenuates chemotactic responses in rhinovirus-induced exacerbation of allergic airways disease by modulating protein phosphatase 2A  Luke."

Similar presentations

Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore–induced allergic airway disease  Ana Paula Moreira, PhD, Karen A.

Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore–induced allergic airway disease  Ana Paula Moreira, PhD, Karen A.
Doina M. Racila, MD, Joel N. Kline, MD, MSc 

Doina M. Racila, MD, Joel N. Kline, MD, MSc 
Glucagon-like peptide 1 receptor signaling attenuates respiratory syncytial virus– induced type 2 responses and immunopathology  Melissa H. Bloodworth,

Glucagon-like peptide 1 receptor signaling attenuates respiratory syncytial virus– induced type 2 responses and immunopathology  Melissa H. Bloodworth,
Maternal immune response to helminth infection during pregnancy determines offspring susceptibility to allergic airway inflammation  Kathrin Straubinger,

Maternal immune response to helminth infection during pregnancy determines offspring susceptibility to allergic airway inflammation  Kathrin Straubinger,
IL-4 induces IL-13–independent allergic airway inflammation

IL-4 induces IL-13–independent allergic airway inflammation
Effective prevention and therapy of experimental allergic asthma using a GATA-3– specific DNAzyme  Serdar Sel, MD, Michael Wegmann, PhD, Tanja Dicke, MSc,

Effective prevention and therapy of experimental allergic asthma using a GATA-3– specific DNAzyme  Serdar Sel, MD, Michael Wegmann, PhD, Tanja Dicke, MSc,
Tze Khee Chan, BSc, Xin Yi Loh, BSc, Hong Yong Peh, BSc, W. N

Tze Khee Chan, BSc, Xin Yi Loh, BSc, Hong Yong Peh, BSc, W. N
Santa Jeremy Ono, BA, PhD, Mark B. Abelson, MD 

Santa Jeremy Ono, BA, PhD, Mark B. Abelson, MD 
The role of viruses in acute exacerbations of asthma

The role of viruses in acute exacerbations of asthma
Virus-specific IgE enhances airway responsiveness on reinfection with respiratory syncytial virus in newborn mice  Azzeddine Dakhama, PhD, Young-Mok Lee,

Virus-specific IgE enhances airway responsiveness on reinfection with respiratory syncytial virus in newborn mice  Azzeddine Dakhama, PhD, Young-Mok Lee,
Innate IL-13–producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity  Jillian L. Barlow, PhD, Agustin Bellosi,

Innate IL-13–producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity  Jillian L. Barlow, PhD, Agustin Bellosi,
Expression of IL-4 receptor α on smooth muscle cells is not necessary for development of experimental allergic asthma  Frank Kirstein, PhD, William G.C.

Expression of IL-4 receptor α on smooth muscle cells is not necessary for development of experimental allergic asthma  Frank Kirstein, PhD, William G.C.
Frank Kirstein, PhD, Natalie E

Frank Kirstein, PhD, Natalie E
IL-33 dysregulates regulatory T cells and impairs established immunologic tolerance in the lungs  Chien-Chang Chen, PhD, Takao Kobayashi, PhD, Koji Iijima,

IL-33 dysregulates regulatory T cells and impairs established immunologic tolerance in the lungs  Chien-Chang Chen, PhD, Takao Kobayashi, PhD, Koji Iijima,
Restoration of T-box–containing protein expressed in T cells protects against allergen- induced asthma  Jung Won Park, MD, Hyun Jung Min, MS, Jung Ho Sohn,

Restoration of T-box–containing protein expressed in T cells protects against allergen- induced asthma  Jung Won Park, MD, Hyun Jung Min, MS, Jung Ho Sohn,
Peter J. Barnes, FMedSci, FRS 

Peter J. Barnes, FMedSci, FRS 
Antigen-specific effector CD8 T cells regulate allergic responses via IFN-γ and dendritic cell function  Yafang Tang, BSc, Shou Ping Guan, BSc, Benson.

Antigen-specific effector CD8 T cells regulate allergic responses via IFN-γ and dendritic cell function  Yafang Tang, BSc, Shou Ping Guan, BSc, Benson.
CD1d restricted natural killer T cells are not required for allergic skin inflammation  Abdallah Elkhal, PhD, Muriel Pichavant, PhD, Rui He, PhD, Jordan.

CD1d restricted natural killer T cells are not required for allergic skin inflammation  Abdallah Elkhal, PhD, Muriel Pichavant, PhD, Rui He, PhD, Jordan.
Β-Glucan exacerbates allergic asthma independent of fungal sensitization and promotes steroid-resistant TH2/TH17 responses  Zhonghua Zhang, MD, Jocelyn.

Β-Glucan exacerbates allergic asthma independent of fungal sensitization and promotes steroid-resistant TH2/TH17 responses  Zhonghua Zhang, MD, Jocelyn.
Allergic airway disease is unaffected by the absence of IL-4Rα–dependent alternatively activated macrophages  Natalie E. Nieuwenhuizen, PhD, Frank Kirstein,

Allergic airway disease is unaffected by the absence of IL-4Rα–dependent alternatively activated macrophages  Natalie E. Nieuwenhuizen, PhD, Frank Kirstein,

Similar presentations

Ads by Google