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Tumor necrosis factor-alpha modulates the expression of its p60 receptor and several cytokines in rat tracheal epithelial cells.

T Bader and P Nettesheim
J Immunol October 1, 1996, 157 (7) 3089-3096;
T Bader
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Abstract

The epithelium of the conducting airways is frequently the target of toxic chemical and microbial agents causing inflammation, hypersecretion, and epithelial necrosis. TNF-alpha is a prototypical inflammatory cytokine released by macrophages and other inflammatory cells. The purpose of this study was to characterize TNF-alpha receptors in fully differentiated rat tracheal epithelial (RTE) cells in culture and to examine the effects of TNF-alpha on this epithelium. We demonstrated the presence of approximately 250 TNF-alpha receptors per RTE cell. Both known receptor types, p60 (TNF-RI, CD 120a) and p80 (TNF-RII, CD 120b), were expressed. The level of p80 mRNA was unaffected by TNF-alpha treatment, whereas p60 mRNA was down-regulated, and soluble TNF-RI was shed from cells within 30 min. Treatment of RTE cultures with TNF-alpha (1000 U) caused no cytotoxicity (as determined by lactate dehydrogenase release). However, TNF-alpha exposure of the cultures induced the expression of several inflammatory mediators, as determined by reverse transcription-PCR and ELISA. Low levels of IFN-gamma mRNA became detectable after 4 h. Increased levels of TNF-alpha mRNA and protein were found, which peaked after 6 h of TNF-alpha treatment, but neither IL-1 alpha nor IL-1 beta was detectable. Calcium-independent nitric oxide synthase transcripts were elevated two- to threefold within 2 to 6 h of TNF-alpha treatment. These findings suggest that the airway epithelium may actively participate in the pathogenesis of airway inflammation through the production of mediators similar to those found in a Th1 response.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 157, Issue 7
1 Oct 1996
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Tumor necrosis factor-alpha modulates the expression of its p60 receptor and several cytokines in rat tracheal epithelial cells.
T Bader, P Nettesheim
The Journal of Immunology October 1, 1996, 157 (7) 3089-3096;

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Tumor necrosis factor-alpha modulates the expression of its p60 receptor and several cytokines in rat tracheal epithelial cells.
T Bader, P Nettesheim
The Journal of Immunology October 1, 1996, 157 (7) 3089-3096;
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Print ISSN 0022-1767        Online ISSN 1550-6606