Differential expression of IL-10 receptor by epithelial cells and alveolar macrophages.
BACKGROUND
Interleukin (IL)-10 is a pleiotropic cytokine with a broad spectrum of immunosuppressive and anti-inflammatory effects. IL-10 secretion from alveolar macrophages is defective in patients with asthma and lower concentrations of IL-10 are found in bronchoalveolar lavage (BAL) from asthmatic patients than in normal control subjects. Reduced IL-10 may result in exaggerated and more prolonged inflammatory responses in asthmatic airways. IL-10 acting through the IL-10 receptor (IL-10R) stimulates the transcription factors STAT1 and STAT3.


METHODS
We investigated IL-10 and IL-10R expression in normal and asthmatic bronchial epithelium and BAL macrophages using reverse transcription-polymerase chain reaction, immunohistochemistry and Western blotting. The functional effect of IL-10 was examined using granulocyte-macrophage-colony stimulating factor, enzyme-linked immunosorbent assay and Western blotting for phosphorylated STAT1 and STAT3.


RESULTS
IL-10 was not expressed in epithelial cells; furthermore these cells did not express the IL-10R and had no functional response to exogenous IL-10. Bronchial epithelial cells expressed variable levels of phosphorylated STAT1 and STAT3 with no change in expression between normal subjects and asthmatics. IL-10 protein and IL-10R expression was detected in alveolar macrophages from all subjects.


CONCLUSIONS
Our study suggests that the bronchial epithelium is not a source of IL-10 and cannot respond to exogenous IL-10 because of a lack of IL-10R expression.
Lim
S
S
Department of Thoracic Medicine, Imperial College School of Medicine, National Heart and Lung Institute, Dovehouse Street, London, UK.
Caramori
G
G
Tomita
K
K
Jazrawi
E
E
Oates
T
T
Chung
K F
KF
Barnes
P J
PJ
Adcock
I M
IM
D000328:Adult; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D018123:Receptors, Interleukin / Q000378:metabolism*; D053701:Receptors, Interleukin-10; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D016209:Interleukin-8; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; D015534:Trans-Activators; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor