Expression of transforming growth factor beta (TGF-β1) in human epithelial alveolar cells:: a pro-inflammatory mediator independent pathway

被引:29
作者
Kwong, KYC
Literat, A
Zhu, NL
Huang, HH
Li, C
Jones, CA
Minoo, P
机构
[1] LAC&USC Med Ctr, Div Allergy Immunol, Dept Pediat, Los Angeles, CA 90033 USA
[2] Los Angeles Cty & Univ So Calif Med Ctr, Div Basic Res, Dept Pediat, Los Angeles, CA USA
关键词
transforming growth factor beta 1; human epithelial alveolar cells; inflammation; NF-Kappa b; AP-1;
D O I
10.1016/j.lfs.2003.08.048
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Regulation of transforming growth factor beta 1 (TGF-beta1) expression remains unclear. Inflammation has been inferred to play a major role in stimulating TGF-beta1 production since high concentrations of TGF-beta1 have been found in the lungs of patients with various diffuse inflammatory lung diseases. To establish an association between inflammation and TGF-beta1 expression, human alveolar epithelial (A549) cells were co-cultured with lipopolysaccharide (LPS), Tumor necrosis factor alpha (TNFalpha), Interleukin 1 beta (IL-1beta) and Interleukin 8 (IL-8) for 12 hours. Total and bioactive TGF-beta1 protein were then measured. A549 cells transiently transfected with a plasmid containing the TGF-beta1 promoter linked to a luciferase reported gene were then co-cultured with the same inflammatory peptides for 12 hours and TGF-beta1 promoter activity determined. Nuclear transcription factors AP-1 (c-jun) or NF-kappa (p65, p50 and p105) were over expressed in A549 cells transiently transfected with the TGF-beta1 promoter and TGF-beta1 promoter activity subsequently measured. Stimulation with inflammatory signals LPS, TNFalpha, IL-1beta, IL-8 resulted in no increase of total or bioactive TGF-beta1 activity above constitutive concentrations in vitro. TGF-beta1 promoter activity was also unchanged from baseline levels in response to the same inflammatory peptides. Expression of c-jun however led to significant increases of TGF-beta1 promoter activity over constitutive levels. In contrast p65 and p105 expression resulted in inhibition of TGF-beta1 promoter activity below baseline levels. We conclude that in a human alveolar epithelial cell line, inflammation does not regulate TGF-beta1 expression. These studies suggest that in lung pathologies such as asthma,jung fibrosis and CLD, TGF-beta1 production may involve pathways independent of inflammatory mediators LPS, TNFalpha, IL-1beta and IL-8. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:2941 / 2957
页数:17
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