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This Article Full Text Full Text (PDF) All Versions of this Article: 286/4/L777    most recent 00289.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Takamura, K. Articles by Nishimura, M. Search for Related Content PubMed PubMed Citation Articles by Takamura, K. Articles by Nishimura, M.

Retinoic acid inhibits interleukin-4-induced eotaxin production in a human bronchial epithelial cell line

¹First Department of Medicine, Hokkaido University School of Medicine, Sapporo 060-8638; ²First Department of Internal Medicine, Showa University, Tokyo 142-8555, Japan; and ³Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224-6801

Submitted 26 August 2003 ; accepted in final form 3 December 2003

Retinoic acid (RA) is known to accelerate wound healing and induce cell differentiation. All-trans RA (ATRA) exerts its effect by binding retinoic acid receptors, which are members of the nuclear receptor family. We investigated whether RA can alter expression of eotaxin, a potent eosinophil chemoattractant that is regulated by the transcription factors signal transducer and activator of transcription 6 (STAT6) and NF-B. We examined the effects of RA on eotaxin expression in a human bronchial epithelial cell line BEAS-2B. ATRA and its stereodimer 9-cis retinoic acid (9-cis RA) inhibited IL-4-induced release of eotaxin at 10^-6 M by 78.0 and 52.0%, respectively (P < 0.05). ATRA and 9-cis RA also significantly inhibited IL-4-induced eotaxin mRNA expression at 10^-6 M by 52.3 and 53.5%, respectively (P < 0.05). In contrast, neither ATRA nor 9-cis RA had any effects on TNF--induced eotaxin production. In transfection studies using eotaxin promoter luciferase plasmids, the inhibitory effect of ATRA on IL-4-induced eotaxin production was confirmed at the transcriptional level. Interestingly, ATRA had no effects on IL-4-induced tyrosine phosphorylation, nuclear translocation, or DNA binding activity of STAT6. Activating protein-1 was not involved in ATRA-mediated transrepression of eotaxin with IL-4 stimulation. The mechanism of the inhibitory effect of ATRA on IL-4-induced eotaxin production in human bronchial epithelial cells has not been elucidated but does not appear to be due to an effect on STAT6 activation. These findings raise the possibility that RA may reduce eosinophilic airway inflammation, one of the prominent pathological features of allergic diseases such as bronchial asthma.

all-trans retinoic acid; 9-cis retinoic acid; eotaxin; signal transducer and activator of transcription 6