title: Vitamin A differentially regulates cytokine expression in respiratory epithelial and macrophage cell lines.
abstract: Vitamin A is an essential nutrient for the protection of children from respiratory tract disease. Supplementation with vitamin A is frequently prescribed in the clinical setting, in part to combat deficiencies among children in developing countries, and in part to treat respiratory infections in clinical trials. This vitamin influences immune responses via multiple, and sometimes seemingly contradictory mechanisms. For example, in separate reports, vitamin A was shown to decrease Th17 T-cell activity by downregulating IL-6, and to promote B cell production of IgA by upregulating IL-6. To explain these apparent contradictions, we evaluated the effects of retinoic acid (RA), a key metabolite of vitamin A, on cell lines of respiratory tract epithelial cells (LETs) and macrophages (MACs). When triggered with LPS or Sendai virus, a mouse respiratory pathogen, these two cell lines experienced opposing influences of RA on IL-6. Both IL-6 protein production and transcript levels were downregulated by RA in LETs, but upregulated in MACs. RA also increased transcript levels of MCP-1, GMCSF, and IL-10 in MACs, but not in LETs. Conversely, when LETs, but not MACs, were exposed to RA, there was an increase in transcripts for RARβ, an RA receptor with known inhibitory effects on cell metabolism. Results help explain past discrepancies in the literature by demonstrating that the effects of RA are cell target dependent, and suggest close attention be paid to cell-specific effects in clinical trials involving vitamin A supplements.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Rhiannon R
authors.initials: RR
authors.lastname: Penkert
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Bart G
authors.initials: BG
authors.lastname: Jones
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Häcker
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Janet F
authors.initials: JF
authors.lastname: Partridge
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA. Electronic address: julia.hurwitz@stjude.org.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Hurwitz
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D016207:Cytokines / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D014801:Vitamin A / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D014801:Vitamin A
keywords: Epithelial cell; IL-6; Macrophage; Respiratory tract; Vitamin A