GM-CSF increases AP-1 DNA binding and Ref-1 amounts in human alveolar macrophages.
Am J Respir Cell Mol Biol
; 25(2): 254-9, 2001 Aug.
Article
en En
| MEDLINE
| ID: mdl-11509337
ABSTRACT
Alveolar macrophages have been implicated in the pathogenesis of a number of acute and chronic lung disorders. A characteristic feature of many of the chronic lung diseases is that the types of macrophages in the lung change, and in most instances, the cells resemble monocyte-like cells. We have previously shown that normal human alveolar macrophages have a decreased capacity to express protein kinase C (PKC)-induced DNA binding activity of the transcription factor activator protein (AP)-1 compared with monocytes. This decrease in AP-1 DNA binding appears to be due to a defect in redox regulation of AP-1 proteins via a decrease in the redox active protein Ref-1. The hypothesis for this study is that there are factors generated during the development of chronic lung disease that increase AP-1 DNA binding activity and Ref-1 production in human alveolar macrophages. We have focused specifically on granulocyte-macrophage colony-stimulating factor (GM-CSF) as a prototype mediator that can be released by alveolar macrophages and is related to the fibrotic process in the lung. We found that after a 24-h incubation with GM-CSF, AP-1 DNA binding was significantly increased in both unstimulated, interleukin (IL)-13, and phorbol myristate acetate (PMA)-stimulated alveolar macrophages and that there was a corresponding increase in Ref-1 protein by Western blot analysis in the PMA-stimulated group. This suggests that disease-related cytokines such as GM-CSF and IL-13 may modulate AP-1 DNA binding activity in alveolar macrophages.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN
/
Factor Estimulante de Colonias de Granulocitos y Macrófagos
/
Macrófagos Alveolares
/
Factor de Transcripción AP-1
/
Liasas de Carbono-Oxígeno
/
ADN-(Sitio Apurínico o Apirimidínico) Liasa
Límite:
Humans
Idioma:
En
Revista:
Am J Respir Cell Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos