Calcitriol decreases expression of importin α3 and attenuates RelA translocation in human bronchial smooth muscle cells.
Calcitriol decreases expression of importin α3 and attenuates RelA translocation in human bronchial smooth muscle cells.
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DOI：
10.1007/s10875-012-9696-x
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发表时间：
2012-10
影响因子：
9.1
通讯作者：
Agrawal, Devendra K.
中科院分区：
文献类型：
--
作者：
Agrawal, Tanupriya;Gupta, Gaurav K.;Agrawal, Devendra K.
关键词：
维生素D在先天免疫和适应性免疫中的有效免疫调节作用最近得到了重视。在变应性哮喘中，NF-κB的活化诱导参与变应性气道炎症的各种细胞因子和趋化因子的转录。活化的NF-κB p50/RelA亚单位的核输入依赖于输入素α3（importin α 4，KPNA 3）和输入素α4（importin α4，KPNA 4）。本研究探讨了importin α3在骨化三醇对人支气管平滑肌细胞（HBSMCs）免疫调节作用中的作用。在存在和不存在细胞因子TNF-α、IL-1β和IL-10的情况下，用骨化三醇刺激培养的HBSMC。使用qPCR分析importin α3和α4的mRNA转录物，同时通过免疫印迹分析importin α3、α4和核RelA的蛋白表达。骨化三醇显著降低importin α3 mRNA和蛋白表达及NF-κB p65（RelA）核蛋白表达。通过骨化三醇处理后HBSMC释放RelA诱导分子（包括IL-5、IL-6和IL-8）的减少证实了骨化三醇对RelA活化的减少。骨化三醇可减弱TNF-α和IL-1β上调importin α3 mRNA和蛋白表达的作用。IL-10显著降低TNF-α诱导的importin α3的表达，骨化三醇进一步增强这种作用。这些数据表明，在炎症条件下，骨化三醇降低importin α3的表达，导致活化RelA的核输入减少。这可能是骨化三醇发挥其免疫调节作用减轻过敏性哮喘气道炎症从而缓解症状的一种新机制。
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). 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. Calcitriol significantly decreased mRNA and protein expression of importin α3 as well as nuclear protein expression of NF-κB 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-α induced expression of importin α3 and this effect was further potentiated by calcitriol. 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.
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影响因子：
13.5
作者：
Edwards MR;Bartlett NW;Clarke D;Birrell M;Belvisi M;Johnston SL
通讯作者：
Johnston SL
影响因子：
4.4
作者：
Giarratana, N;Penna, G;Adorini, L
通讯作者：
Adorini, L
影响因子：
5.3
作者：
HOHMANN, HP;REMY, R;VANLOON, APGM
通讯作者：
VANLOON, APGM
影响因子：
3.5
作者：
Harant, H;Wolff, B;Lindley, IJD
通讯作者：
Lindley, IJD
影响因子：
14.2
作者：
Agrawal, DK;Ariyarathna, K;Kelbe, PW
通讯作者：
Kelbe, PW