Calcitriol decreases expression of importin α3 and attenuates RelA translocation in human bronchial smooth muscle cells

Tanupriya Agrawal, Gaurav K. Gupta, Devendra K. Agrawal

    Research output: Contribution to journalArticlepeer-review

    27 Scopus citations

    Abstract

    Purpose: A potent immunomodulatory role of Vitamin D in both innate and adaptive immunity has recently been appreciated. In allergic asthma, activation of NF-κB induces transcription of various cytokines and chemokines involved in allergic airway inflammation. The nuclear import of activated NF-κB p50/RelA subunit is dependent on importin α3 (KPNA4) and importin α4 (KPNA3). In this study, we examined the role of importin α3 in immunomodulatory effect of calcitriol in human bronchial smooth muscle cells (HBSMCs). Methods Cultured HBSMCs were stimulated with calcitriol in the presence and absence of cytokines, TNF-α, IL-1β, and IL-10. The mRNA transcripts of importin α3 and α4 were analyzed using qPCR while protein expression of importin α3, α4 and nuclear RelA was analyzed by immunoblotting. Results Calcitriol significantly decreased mRNA and protein expression of importin α3 as well as nuclear protein expression of NF-KB p65 (RelA). The decreased activation of RelA by calcitriol was confirmed by decreased release of RelA-inducible molecules, including IL-5, IL-6 and IL-8, by HBSMCs upon calcitriol treatment. Calcitriol attenuated the effect of TNF-α and IL-1β to upregulate mRNA and protein expression of importin α3. IL-10 significantly decreased the TNF-a induced expression of importin a3 and this effect was further potentiated by calcitriol. Conclusions These data suggest that under inflammatory conditions, calcitriol decreases the expression of importin α3 resulting in decreased nuclear import of activated RelA. This could be a novel mechanism by which calcitriol could exert its immunomodulatory effects to reduce allergic airway inflammation and thus may alleviate the symptoms in allergic asthma.

    Original languageEnglish
    Pages (from-to)1093-1103
    Number of pages11
    JournalJournal of Clinical Immunology
    Volume32
    Issue number5
    DOIs
    StatePublished - Oct 2012

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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