Interleukin-1-beta gene expression in human monocytes and alveolar macrophages from normal subjects and patients with sarcoidosis.
To assess the ability of human alveolar macrophages to produce interleukin-1-beta (IL1-beta), we examined IL1-beta mRNA accumulation in autologous monocytes and alveolar macrophages from normal volunteers. Escherichia coli lipopolysaccharide stimulation of monocytes induced rapid IL1-beta mRNA accumulation, reaching a maximum at 2 to 4 h and declining thereafter. Alveolar macrophages, however, accumulated much less mRNA than did monocytes. This difference could not be explained by differences in kinetics of IL1-beta gene expression between the 2 cell types, isolation techniques, or alveolar macrophage lidocaine exposure. This suggests that differences in transcription of the IL1-beta gene exist between these 2 cell types. Aging is a possible factor important in some functional differences between these 2 cell types. To determine if this difference in the capacity to express the IL1-beta gene might be a function of cell maturity, monocytes were aged in vitro for 7 days. After this culture period, monocytes had a marked decrease in the ability to accumulate IL1-beta mRNA, suggesting that cell aging may be one mechanism involved in producing these transcriptional differences. Because IL1-beta has also been implicated in the inflammatory and fibrotic responses in pulmonary sarcoidosis, 4 patients with newly diagnosed sarcoidosis underwent bronchoalveolar lavage, and IL1-beta mRNA accumulation was compared in their alveolar macrophages and blood monocytes. Comparing normal alveolar macrophages to those from patients with sarcoidosis showed no differences in the kinetics of IL1-beta mRNA expression or in the LPS-induced levels of IL1-beta mRNA accumulation. In addition, augmented levels of IL1-beta transcript were not noted in unstimulated sarcoid alveolar macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
Kern
J A
JA
Department of Medicine, Hospital University of Pennsylvania, Philadelphia 19104-4283.
Lamb
R J
RJ
Reed
J C
JC
Elias
J A
JA
Daniele
R P
RP
D015152:Blotting, Northern; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008264:Macrophages; D009000:Monocytes; D011650:Pulmonary Alveoli / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D012507:Sarcoidosis / Q000235:genetics*
D007375:Interleukin-1; D012333:RNA, Messenger