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Expression of transforming growth factor beta (TGF-beta1) in human epithelial alveolar cells: a pro-inflammatory mediator independent pathway.
Life Sci. 2004 Apr 30; 74(24):2941-57.LS

Abstract

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, lung fibrosis and CLD, TGF-beta1 production may involve pathways independent of inflammatory mediators LPS, TNFalpha, IL-1beta and IL-8.

Authors+Show Affiliations

Division of Allergy-Immunology, Department of Pediatrics, LAC+USC Medical Center, Room 1G1 General Labs Building, 1801 E Marengo St, Los Angeles, CA 90033, USA. kkwongusc@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15051419

Citation

Kwong, K Y C., et al. "Expression of Transforming Growth Factor Beta (TGF-beta1) in Human Epithelial Alveolar Cells: a Pro-inflammatory Mediator Independent Pathway." Life Sciences, vol. 74, no. 24, 2004, pp. 2941-57.
Kwong KY, Literat A, Zhu NL, et al. Expression of transforming growth factor beta (TGF-beta1) in human epithelial alveolar cells: a pro-inflammatory mediator independent pathway. Life Sci. 2004;74(24):2941-57.
Kwong, K. Y., Literat, A., Zhu, N. L., Huang, H. H., Li, C., Jones, C. A., & Minoo, P. (2004). Expression of transforming growth factor beta (TGF-beta1) in human epithelial alveolar cells: a pro-inflammatory mediator independent pathway. Life Sciences, 74(24), 2941-57.
Kwong KY, et al. Expression of Transforming Growth Factor Beta (TGF-beta1) in Human Epithelial Alveolar Cells: a Pro-inflammatory Mediator Independent Pathway. Life Sci. 2004 Apr 30;74(24):2941-57. PubMed PMID: 15051419.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of transforming growth factor beta (TGF-beta1) in human epithelial alveolar cells: a pro-inflammatory mediator independent pathway. AU - Kwong,K Y C, AU - Literat,A, AU - Zhu,N L, AU - Huang,H H, AU - Li,C, AU - Jones,C A, AU - Minoo,P, PY - 2003/07/07/received PY - 2003/08/25/accepted PY - 2004/3/31/pubmed PY - 2004/4/21/medline PY - 2004/3/31/entrez SP - 2941 EP - 57 JF - Life sciences JO - Life Sci. VL - 74 IS - 24 N2 - 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, lung fibrosis and CLD, TGF-beta1 production may involve pathways independent of inflammatory mediators LPS, TNFalpha, IL-1beta and IL-8. SN - 0024-3205 UR - https://www.unboundmedicine.com/medline/citation/15051419/Expression_of_transforming_growth_factor_beta__TGF_beta1__in_human_epithelial_alveolar_cells:_a_pro_inflammatory_mediator_independent_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024320504001183 DB - PRIME DP - Unbound Medicine ER -