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

Kei Takamura, Yasuyuki Nasuhara, Motoko Kobayashi, Tomoko Betsuyaku, Yoko Tanino, Ichiro Kinoshita, Etsuro Yamaguchi, Satoshi Matsukura, Robert P. Schleimer, Masaharu Nishimura

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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-κB. 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-α-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.

Original languageEnglish
Pages (from-to)L777-L785
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume286
Issue number4 30-4
DOIs
Publication statusPublished - 2004 Apr

Keywords

  • 9-cis retinoic acid
  • All-trans retinoic acid
  • Eotaxin
  • Signal transducer and activator of transcription 6

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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