A modeling-derived hypothesis on chronicity in respiratory diseases: desensitized pathogen recognition secondary to hyperactive IRAK/TRAF6 signaling.
PLoS One
; 4(4): e5332, 2009.
Article
em En
| MEDLINE
| ID: mdl-19390631
ABSTRACT
Several chronic respiratory diseases exhibit hyperactive immune responses in the lung abundant inflammatory mediators; infiltrating neutrophils, macrophages, lymphocytes and other immune cells; and increased level of proteases. Such diseases include cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and severe/neutrophilic asthma. Paradoxically, patients with these diseases are also susceptible to detrimental bacterial infection and colonization. In this paper, we seek to explain how a positive feedback mechanism via IL-8 could lead to desensitization of epithelial cells to pathogen recognition thus perpetuating bacterial colonization and chronic disease states in the lung. Such insight was obtained from mathematical modeling of the IRAK/TRAF6 signaling module, and is consistent with existing clinical evidence. The potential implications for targeted treatment regimes for these persistent respiratory diseases are explored.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtornos Respiratórios
/
Transdução de Sinais
/
Fator 6 Associado a Receptor de TNF
/
Quinases Associadas a Receptores de Interleucina-1
/
Modelos Biológicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos