Interleukin-26 in antibacterial host defense of human lungs. Effects on neutrophil mobilization.
Am J Respir Crit Care Med
; 190(9): 1022-31, 2014 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-25291379
ABSTRACT
RATIONALE The role of the presumed Th17 cytokine IL-26 in antibacterial host defense of the lungs is not known. OBJECTIVES:
To characterize the role of IL-26 in antibacterial host defense of human lungs.METHODS:
Intrabronchial exposure of healthy volunteers to endotoxin and vehicle was performed during bronchoscopy and bronchoalveolar lavage (BAL) samples were harvested. Intracellular IL-26 was detected using immunocytochemistry and immunocytofluorescence. This IL-26 was also detected using flow cytometry, as was its receptor complex. Cytokines and phosphorylated signal transducer and activator of transcription (STAT) 1 plus STAT3 were quantified using ELISA. Gene expression was analyzed by real-time polymerase chain reaction and neutrophil migration was assessed in vitro. MEASUREMENTS AND MAINRESULTS:
Extracellular IL-26 was detected in BAL samples without prior exposure in vivo and was markedly increased after endotoxin exposure. Alveolar macrophages displayed gene expression for, contained, and released IL-26. Th and cytotoxic T cells also contained IL-26. In the BAL samples, IL-26 concentrations and innate effector cells displayed a correlation. Recombinant IL-26 potentiated neutrophil chemotaxis induced by IL-8 and fMLP but decreased chemokinesis for neutrophils. Myeloperoxidase in conditioned media from neutrophils was decreased. The IL-26 receptor complex was detected in neutrophils and IL-26 decreased phosphorylated STAT3 in these cells. In BAL and bronchial epithelial cells, IL-26 increased gene expression of the IL-26 receptor complex and STAT1 plus STAT3. Finally, IL-26 increased the release of neutrophil-mobilizing cytokines in BAL but not in epithelial cells.CONCLUSIONS:
This study implies that alveolar macrophages produce IL-26, which stimulates receptors on neutrophils and focuses their mobilization toward bacteria and accumulated immune cells in human lungs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucinas
/
Macrófagos Alveolares
/
Imunidade Inata
/
Pulmão
/
Neutrófilos
Limite:
Humans
Idioma:
En
Revista:
Am J Respir Crit Care Med
Assunto da revista:
TERAPIA INTENSIVA
Ano de publicação:
2014
Tipo de documento:
Article