Eosinophil Induced Remodelling in Asthma

Summary

Asthma is a chronic, inflammatory disease of the lung characterized by intermittent airway obstruction, airway hyperresponsiveness, presence of activated inflammatory cells, inflammatory mediators, and airway structural changes. Airway smooth muscle (ASM) cells actively participate in the remodelling and inflammatory processes through proliferation, release of proinflammatory cytokines, chemokines, and extracellular matrix (ECM) proteins. Eosinophils as essential inflammatory cells may be of importance in ASM remodelling. It is known that eosinophil induces ASM cells proliferation via the secretion of cysteinyl leukotrienes in asthmatics. However there is a possible direct eosinophil-ASM cells functional interaction by adhesion processes. It has been shown that integrins modulate ASM proliferation and contractile protein expression demonstrating allergen-induced ASM remodelling in an animal model of allergic asthma.

Wingless/integrase-1 (WNT) signaling regulates not only a wide range of developmental processes, but its aberrant activation can lead to disease. Recently, it was confirmed that genes polymorphisms in the WNT signaling pathway are associated with impaired lung function in childhood asthma. It was also found for the first time a relevant role of noncanonical WNT signaling in TGFβ-induced ECM expression by ASM cells and identified WNT-5A is the most abundant WNT ligand with increased expression in asthmatics. It demonstrates that WNT-5A could contribute to remodelling of the airways. Unfortunately, the effect of eosinophil on WNT secretion by ASM cells at present is unknown.

Despite the widely acknowledged significance of eosinophils in asthma pathogenesis, the mechanism of eosinophil induced ASM remodelling is unsolved.

Conditions

• Allergic Asthma
• Airway Remodelling

Interventions

PROCEDURE

Bronchial challenge with allergen

Bronchial challenge is performed with D. pteronyssinus allergen.

OTHER

Co-culture formation

Eosinophil and linear bronchial smooth muscle cell co-culture formation. Airway smooth muscle cell proliferation, eosinophil adhesion to the bronchial smooth muscle cells, the role of eosinophil integrins in the airway remodelling process is assessed in individual formed co-culture

Sponsors & Collaborators

• Research Council of Lithuania

  collaborator OTHER

• University of Groningen

  collaborator OTHER

• Lithuanian University of Health Sciences

  lead OTHER

Principal Investigators

• Kestutis Malakauskas, Prof., dr. · Lithuanian University of Health Sciences, Pulmonology and Immunology Department

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-03-31

Primary Completion

2016-10-31

Completion

2017-01-31

Countries

• Lithuania

Study Locations