IL-6 amplifier activation in epithelial regions of bronchi after allogeneic lung transplantation.
Int Immunol
; 25(5): 319-32, 2013 May.
Article
em En
| MEDLINE
| ID: mdl-23396843
ABSTRACT
The IL-6 amplifier, a positive feedback loop for NFκB signaling, which was originally found to be activated by IL-17A and IL-6 stimulation in non-immune cells, is molecularly a simultaneous activator of NFκB and signal transducer and activator of transcription 3 (STAT3), functionally a local chemokine inducer and pathologically a machinery for inflammation development. It has been shown that IL-6 amplifier activation in epithelial cells contributes to rejection responses in a mouse chronic rejection model that develops a bronchiolitis obliterans (BO)-like disease. We investigated whether the IL-6 amplifier is activated in BO regions of a human lung graft after allogeneic transplantation. NFκB and STAT3 molecules were phosphorylated in the epithelial regions of bronchi that localized in the BO regions. Additionally, chemokine ligand 2 (CCL2), and CD4(+) T cells and macrophages increased in these regions. Furthermore, human lung epithelial cells expressed CCL2 after stimulation by IFNγ in the presence of IL-6 and epidermal growth factor via enhanced STAT3 signaling, which parallels behavior seen in the mouse model. Thus, our results suggest that the IL-6 amplifier in the epithelial cells of grafts is involved in chronic rejection after lung transplantation, suggesting that the amplifier may be a valuable therapeutic target to prevent chronic rejection after lung transplantation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Brônquios
/
Bronquiolite Obliterante
/
Interleucina-6
/
Transplante de Pulmão
/
Células Epiteliais
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Int Immunol
Ano de publicação:
2013
Tipo de documento:
Article