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 journalArticle

24 Citations (Scopus)

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

Fingerprint

Karyopherins
Calcitriol
Smooth Muscle Myocytes
Cell Nucleus Active Transport
Interleukin-1
Interleukin-10
Messenger RNA
Asthma
Cytokines
Inflammation
Proteins
Interleukin-5
Adaptive Immunity
Nuclear Proteins
Interleukin-8
Chemokines
Immunoblotting
Innate Immunity
Vitamin D
Interleukin-6

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Calcitriol decreases expression of importin α3 and attenuates RelA translocation in human bronchial smooth muscle cells. / Agrawal, Tanupriya; Gupta, Gaurav K.; Agrawal, Devendra K.

In: Journal of Clinical Immunology, Vol. 32, No. 5, 10.2012, p. 1093-1103.

Research output: Contribution to journalArticle

@article{a5d6b53564bb4edcac3e162f745ae01f,
title = "Calcitriol decreases expression of importin α3 and attenuates RelA translocation in human bronchial smooth muscle cells",
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.",
author = "Tanupriya Agrawal and Gupta, {Gaurav K.} and Agrawal, {Devendra K.}",
year = "2012",
month = "10",
doi = "10.1007/s10875-012-9696-x",
language = "English",
volume = "32",
pages = "1093--1103",
journal = "Journal of Clinical Immunology",
issn = "0271-9142",
publisher = "Springer New York",
number = "5",

}

TY - JOUR

T1 - Calcitriol decreases expression of importin α3 and attenuates RelA translocation in human bronchial smooth muscle cells

AU - Agrawal, Tanupriya

AU - Gupta, Gaurav K.

AU - Agrawal, Devendra K.

PY - 2012/10

Y1 - 2012/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84866742257&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866742257&partnerID=8YFLogxK

U2 - 10.1007/s10875-012-9696-x

DO - 10.1007/s10875-012-9696-x

M3 - Article

VL - 32

SP - 1093

EP - 1103

JO - Journal of Clinical Immunology

JF - Journal of Clinical Immunology

SN - 0271-9142

IS - 5

ER -