The role of microfibrillar-associated protein 4 (MFAP4) in asthma Bartosz Pilecki PhD student Institute of Molecular Medicine University of Southern Denmark,

Slides:

Advertisements

Similar presentations

ASTHMA A. K. Nayyar. Definition It is a syndrome characterized by AIRFLOW OBSTRUCTION that varies markedly, both spontaneously and with treatment. Narrowing.

Advertisements

On-going Research Studies in the Rosenfeld Lab *The role of RANK/RANKL in vascular complications of chronic kidney disease Effects of air pollution (diesel.

The Role of Aryl Hydrocarbon Receptor (AhR) in the Immune System of Aging Mice Duy Pham Dr. Nancy I. Kerkvliet Department of Environmental and Molecular.

The impact of allergic rhinitis on asthma Gert-Jan Braunstahl Pulmonary medicine, EMCR, Rotterdam.

BRONCHIAL ASTHMA YOUSEF ABDULLAH AL TURKI MBBS,DPHC,ABFM

Asthma Michelle Anderson And Alex Barker. What is Asthma? Description Asthma is a complex, recurrent disease of the airways that causes shortness of breath,

Asthma & Exercise Physiology and Pathophysiology

Ever Orlando Salaiz Acuna Period  Asthma - This disease of the affects breathing by mucus that runs down the trachea.  It affects the lungs.

Immunology of Asthma Immunology Unit Department of Pathology King Saud University.

Immunology of Asthma Dr. Hend Alotaibi Assistant Professor & Consultant College of Medicine, King Saud University Dermatology Department /KKUH

Asthma By: Emily Ngo. Asthma Background Asthma is a chronic disease that affects up to 150 million people in the world Asthma is an inflammatory disease.

KRISTEN DOSTIE Alteration of Chemotaxis in the Gut of IBD Patients.

STAT3 and the Immune System Maureen Sherry Lynes February 29, 2012.

Functional Effects of TGF-beta1 on Mesenchymal Stem Cell Mobilization in Cockroach Allergen Induced Asthma Pei-Song Gao, MD, PhD Division of Allergy &

Lecture 16 Allergy Hay fever 20% Asthma ~5%. Figure 10-1.

Effects of blue shark cartilage alkaline extract on cytokine secretions in bronchoalveolar lavage fluid of ovalbumin-sensitized and -challenged mice Mei-Chun.

三重大学医学部病理 Deficiency of tenascin-C attenuates liver

New Strategies of the EPR-3. – Asthma is a chronic inflammatory disorder of the airways – The immunohistopathologic features of asthma include inflammatory.

Prostaglandin D2: Therapeutic Indications World Allergy Organisation Cancun 2011 Andy Wardlaw.

Interactions between viral infections and allergy in exacerbating asthma.

The role of microfibrillar-associated protein 4 (MFAP4) in asthma Bartosz Pilecki PhD student Institute of Molecular Medicine University of Southern Denmark,

Adenosine Protects Vascular Barrier Function in Hyperoxic Lung Injury Jonathan Davies 1, Harry Karmouty-Quintana 2, Thuy T. Le 2, Ning-Yuan Chen 2, Tingting.

Inhibition of microfibrillar-associated protein 4 as a potential therapy targeting choroidal neovascularization in age-related macular degeneration Bartosz.

Asthma Review of Pathophysiology and Treatment. n definition of asthma –Asthma is a chronic inflammatory disorder of the airways in which many cells &

Microfibrillar-associated protein 4 is a novel regulator of elastic fiber assembly and integrin-dependent cellular signaling Bartosz Pilecki Institute.

Immunology Unit Department of Pathology King Saud University

Immuno-modulatory mediators Role in asthma

What effect does asthma treatment have on airway remodeling

Research, 2016, Vol. 4, No. 1, doi: /jfnr-4-1-6

Fig. 1. Pathological mechanisms of asthma

Sejal Saglani, MD, Stephen Lui, PhD, Nicola Ullmann, MD, Gaynor A

Connective Tissue Notes

Weiguo Chen, PhD, Umasundari Sivaprasad, PhD, Aaron M

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

Effective prevention and therapy of experimental allergic asthma using a GATA-3– specific DNAzyme Serdar Sel, MD, Michael Wegmann, PhD, Tanja Dicke, MSc,

Virus-specific IgE enhances airway responsiveness on reinfection with respiratory syncytial virus in newborn mice Azzeddine Dakhama, PhD, Young-Mok Lee,

Interferon response factor 3 is essential for house dust mite–induced airway allergy Thomas Marichal, DVM, Denis Bedoret, DVM, PhD, Claire Mesnil, DVM,

Innate IL-13–producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity Jillian L. Barlow, PhD, Agustin Bellosi,

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,

Jennifer L. Ingram, PhD, Monica Kraft, MD

Eosinophils contribute to the resolution of lung-allergic responses following repeated allergen challenge Katsuyuki Takeda, MD, PhD, Yoshiki Shiraishi,

Prime role of IL-17A in neutrophilia and airway smooth muscle contraction in a house dust mite–induced allergic asthma model Julie Chesné, PhD, Faouzi.

CD4+CD25+ regulatory T cells reverse established allergic airway inflammation and prevent airway remodeling Jennifer Kearley, PhD, Douglas S. Robinson,

Effect of caspase-1 deficiency on lung inflammatory parameters and inflammatory cell subsets in a mouse model of asthma exacerbation. Effect of caspase-1.

No Ameliorating Effect of Surfactant Protein D on DSS-Induced Colitis in Mice Anders B. Nexoe1, Bartosz Pilecki1, Mathias Rathe2, Steffen Husby2, Uffe.

CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma Vipul V. Jain, MDa, Kunihiko Kitagaki, PhDa, Thomas Businga,

Innate lymphoid cells in allergic and nonallergic inflammation

Qutayba Hamid, MD, PhD Journal of Allergy and Clinical Immunology

Mast cell–derived plasminogen activator inhibitor type 1 promotes airway inflammation and remodeling in a murine model of asthma Ara Jo, PhD, Sun H.

Protein disulfide isomerase–endoplasmic reticulum resident protein 57 regulates allergen-induced airways inflammation, fibrosis, and hyperresponsiveness

Does reduced zona pellucida binding protein 2 (ZPBP2) expression on chromosome 17q21 protect against asthma? Marina Miller, MD, PhD, Christine Vuong,

TNF-α induces the late-phase airway hyperresponsiveness and airway inflammation through cytosolic phospholipase A2 activation Il-Whan Choi, PhD, Sun-Kim,

The Editors' Choice Journal of Allergy and Clinical Immunology

Recombinant basic fibroblast growth factor inhibits the airway hyperresponsiveness, mucus production, and lung inflammation induced by an allergen challenge

Ilaria Ghia & Fabio Grieco

Novel allergic asthma model demonstrates ST2-dependent dendritic cell targeting by cypress pollen Lucia Gabriele, BS, Giovanna Schiavoni, BS, Fabrizio.

Gross pathology and histopathology of asthma

Stephen T. Holgate, MD, DSca, Marc Peters-Golden, MDb, Reynold A

Immunology Unit Department of Pathology King Saud University

Immunology Unit Department of Pathology King Saud University

Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness Michael R. Edwards, PhD, Katherine Strong,

Thomas Gensollen, PhD, Richard S. Blumberg, MD

Requirement for IL-13 Independently of IL-4 in Experimental Asthma

Innate lymphoid cells in allergic and nonallergic inflammation

House dust mite models: Will they translate clinically as a superior model of asthma? Jonathan E. Phillips, PhD, Ruoqi Peng, MD, Paul Harris, BS, Lisa.

The extra domain A of fibronectin is essential for allergen-induced airway fibrosis and hyperresponsiveness in mice Martin Kohan, MSc, Andres F. Muro,

Fig. 3. The role of DCs and DC-SIGN in HDM allergy

Recombinant basic fibroblast growth factor inhibits the airway hyperresponsiveness, mucus production, and lung inflammation induced by an allergen challenge

Schematic diagram of the potential cellular effects of interleukin (IL)-4/IL-13 on inflammatory and structural cells in asthma. Schematic diagram of the.

Fig. 5. Effects of IL-9 blockade on chronic pulmonary inflammation

Presentation transcript:

The role of microfibrillar-associated protein 4 (MFAP4) in asthma Bartosz Pilecki PhD student Institute of Molecular Medicine University of Southern Denmark, Odense

Asthma Common chronic airway disease Decrease in lung function due to persistent inflammation, airway remodeling and airway hyperresponsiveness (AHR) Current treatments effective only in selected subsets of patients

MFAP4 Extracellular matrix (ECM) protein that binds to elastin and collagen Abundant in heart, lung, skin etc. Promotes proliferation and migration of vascular SMC in an integrin-dependent manner (Schlosser et al, submitted) Wulf-Johansson et al, 2013

Hypothesis: MFAP4 contributes to asthmatic airway disease, mainly due to its interaction with airway smooth muscle cells

In vivo allergy models OVA model:House dust mite (HDM) chronic model: Day: rest 25 ug HDM i.n. 7 weeks

MFAP4 levels are increased in asthma WT OVA WT PBS

MFAP4 deficiency attenuates eosinophilic infiltration

Eosinophil chemoattractants are downregulated in MFAP4-deficient mice

Lack of MFAP4 attenuates mucus production PBS KO OVA WT OVA

MFAP4 contributes to asthmatic smooth muscle deposition

MFAP4 deficiency partially protects from AHR

Conclusions MFAP4 is increased in circulation and BAL of asthmatic mice. MFAP4 contributes to development of experimental asthma by: 1.Attraction of eosinophils through CCL11/CCL24 2.Goblet cell metaplasia 3.Smooth muscle deposition 4.AHR It suggests that MFAP4 can be a potential therapeutic target for allergic asthma.

Acknowledgements Christopher Stevenson, Novartis, UK Jorgen Vestbo, OUH, DK Niels Marcussen, OUH, DK Fonden til laegevidenskabens fremme