title: Tumor necrosis factor-alpha modulates the expression of its p60 receptor and several cytokines in rat tracheal epithelial cells.
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.
authors.affiliation: National Institute of Environmental Health Sciences, Research Triangle Park NC 27709, USA.
authors.forename: T
authors.initials: T
authors.lastname: Bader
authors.forename: P
authors.initials: P
authors.lastname: Nettesheim
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D013047:Specific Pathogen-Free Organisms; D014132:Trachea / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase