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Doctoral Thesis
DOI
10.11606/T.42.2014.tde-12122014-161448
Document
Author
Full name
Esther Borges Florsheim
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Russo, Momtchilo (President)
Campa, Ana
Nunes, Anderson de Sá
Pinto, Frederico Azevedo da Costa
Scharfstein, Julio
Title in Portuguese
Mecanismos envolvidos na indução da inflamação alérgica pulmonar pela serino protease subtilisina.
Keywords in Portuguese
Asma ocupacional
Epitélio
IL-1R
Inflamação pulmonar
MyD88
PAR-2
Sensibilização alérgica
Serino protease
ST2
Subtilisina
Abstract in Portuguese
A asma ocupacional é a forma mais comum de doença pulmonar relacionada ao trabalho e vários dos casos reportados estão correlacionados à exposição de proteases. A serino protease subtilisina foi bastante utilizada na década de 60 e foi a principal responsável pela alta incidência de asma na indústria de detergente. Este projeto visou a desenvolver um modelo murino de inflamação alérgica pulmonar à subtilisina e caracterizar os mecanismos principais envolvidos nessa resposta. A sensibilização e desafio com subtilisina induziu doença alérgica pulmonar, verificada pela eosinofilia às vias aéreas, produção de muco, IgE total, hiper reatividade brônquica e produção de citocinas tipo II no pulmão. Estas respostas foram dependentes da atividade enzimática da subtilisina, PAR-2, receptor de IL-33 ST2, IL-1R e da sinalização via MyD88. Em conjunto, nossos resultados estabelecem um novo modelo experimental de asma ocupacional induzida por subtilisina e fornece os principais mecanismos moleculares responsáveis pela inflamação alérgica.
Title in English
Mechanisms involved in the induction of allergic lung inflammation to serine protease subtilisin.
Keywords in English
Allergic sensitization
Epithelium
IL-1R
Lung inflammation
MyD88
Occupational asthma
Protease-activated receptor (PAR)-2
Serine protease
ST2
Subtilisin
Abstract in English
Occupational asthma is the most common form of pulmonary disease related to work. Most of occupational asthma cases reported are strictly correlated with proteases exposure. Serine protease subtilisin was widely used in the detergent industry during the 60s, which resulted in increased incidence of occupational asthma. We aimed to develop and characterize a murine model of occupational asthma using subtilisin as allergen. Briefly, sensitization and challenge with subtilisin triggered lung allergic inflammation, as accessed by eosinophilic influx to the airways, mucus production, and increased levels of type II cytokines. Subtilisin induced total IgE and airway hyperactivity. Allergic responses to subtilisin were dependent on its serine protease activity, protease-activated receptor (PAR)-2, IL-33 receptor ST2, IL-1R, and Myd88 signaling. Together, these data establish a new murine model of occupational asthma induced by subtilisin and provide the main molecular mechanisms responsible for allergic inflammation.
 
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Release Date
2016-12-15
Publishing Date
2014-12-16
 
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