Beryllium-induced TNF-alpha production is transcription-dependent in chronic beryllium disease.

Beryllium-induced TNF-alpha production is transcription-dependent in chronic beryllium disease. Research Abstract Details 

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Beryllium-induced TNF-alpha production is transcription-dependent in chronic beryllium disease. Abstract Text:

Richard T Sawyer,Andrew P Fontenot,Tristan A Barnes,Charles E Parsons,Brian C Tooker,Lisa A Maier,May M Gillespie,E Brigitte Gottschall,Lori Silveira,James Hagman,Lee S Newman,

Beryllium (Be)-antigen presentation to Be-specific CD4(+) T cells from the lungs of patients with chronic beryllium disease (CBD) results in T cell proliferation and TNF-alpha secretion. We tested the hypothesis that Be-induced, CBD bronchoalveolar lavage (BAL) T cell, transcription-dependent, TNF-alpha secretion was accompanied by specific transcription factor upregulation. After 6 h of Be stimulation, CBD BAL cells produced a median of 883 pg/ml TNF-alpha (range, 608-1,275 pg/ml) versus 198 pg/ml (range, 116-245 pg/ml) by unstimulated cells. After 12 h CBD BAL cells produced a median of 2,963 pg/ml (range, 99-9,424 pg/ml) TNF-alpha versus 55 pg/ml (range, 0-454) by unstimulated cells. Using real-time RT-PCR, Be-stimulated TNF-alpha production at 6 h was preceded by a 5-fold increase in TNF-alpha pre-mRNA copy number:beta-actin copy number (Be median ratio 0.21; unstimulated median ratio 0.04). The median ratio of mature TNF-alpha mRNA:beta-actin mRNA was upregulated 1.4-fold (Be median ratio 0.17; unstimulated median ratio 0.12). Be exposure in the presence of the transcription inhibitor pentoxifylline (PTX) decreased CBD BAL cell TNF-alpha pre-mRNA levels > 60%, whereas treatment with the mRNA splicing inhibitor 2-aminopurine (2AP) decreased levels 40% relative to Be exposure alone. PTX treatment decreased mature TNF-alpha mRNA levels 50% while 2AP decreased levels > 80%, relative to Be exposure alone. Beryllium exposure specifically upregulated transcription factors AP-1 and NF-kappaB. The data suggest that Be exposure induces transcription-dependent TNF-alpha production, potentially due to upregulation of specific transcription factors.

Beryllium-induced TNF-alpha production is transcription-dependent in chronic beryllium disease. Publishing Authors By Initials

RT Sawyer,AP Fontenot,TA Barnes,CE Parsons,BC Tooker,LA Maier,MM Gillespie,EB Gottschall,L Silveira,J Hagman,LS Newman,

For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

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Beryllium-induced TNF-alpha production is transcription-dependent in chronic beryllium disease. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: American journal of respiratory cell and molecular

VOLUME: 36

Page Numbers: 191-200

Journal Abbreviation: Am. J. Respir. Cell Mol. Biol.

ISSN: 1044-1549

DAY: 15

MONTH: 09

YEAR: 2006

Beryllium-induced TNF-alpha production is transcription-dependent in chronic beryllium disease. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8917225

Beryllium-induced TNF-alpha production is transcription-dependent in chronic beryllium disease. Keywords Mesh Terms:

KEYWORDS: Up-Regulation

MESH TERMS: genetics

Chemical & Substance for Abstract: Beryllium-induced TNF-alpha production is transcription-dependent in chronic beryllium disease. Information

Substance Name: Beryllium

Registry Number: 7440-41-7

Grant and Affiliation Information for Beryllium-induced TNF-alpha production is transcription-dependent in chronic beryllium disease.

AFFILIATION: Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado, USA. sawyerr@niaid.nih.gov

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL62410

ACRONYM: HL

MEDLINETA: Am J Respir Cell Mol Biol

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