ADRB2 suppresses IL-13-induced allergic rhinitis inflammatory cytokine regulated by miR-15a-5p

ADRB2 suppresses IL-13-induced allergic rhinitis inflammatory cytokine regulated by miR-15a-5p
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ADRB2 抑制 miR-15a-5p 调节的 IL-13 诱导的过敏性鼻炎炎症细胞因子

DOI:
10.1007/s13577-019-00259-z
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发表时间:
2019-05
期刊:
影响因子:
4.3
通讯作者:
Zhang Junhong
Zhang Junhong
中科院分区:
生物学3区
文献类型:
--
作者:
Wang Li;Lv Qiaoying;Song Xicheng;Jiang Kun;Zhang Junhong

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过敏性鼻炎(AR)是一种常见的过敏性疾病,给患者带来很大的困扰。鼻上皮细胞(NECs)作为吸入的最外层保护层,在AR过敏反应中发挥着重要作用。肾上腺素受体β2(ADRB2)是炎症反应中的重要基因,近年来已成为AR开发和治疗的热点。 MiR-15a-5p已被证明作为ADRB2的上游调节因子参与AR免疫反应。分离人原代 NEC 并用 IL-13 刺激。采用qRT-PCR法检测目的基因的RNA水平。应用ELISA和Western blotting检测目标蛋白水平。进行荧光素酶报告基因测定和生物素下拉测定来测试分子相互作用。 ADRB2在AR患者的鼻粘膜中高表达,并与IL-13刺激呈正相关,敲低ADRB2可抑制IL-13诱导的NECs中GM-CSF、eotaxin和MUC5AC的表达。 ADRB2 是 miR-15a-5p 直接靶向的,并且 miR-15a-5p 抑制 IL-13 诱导的 NEC 中 GM-CSF、eotaxin 和 MUC5AC 的表达。 ADRB2 介导 miR-15a-5p 对鼻上皮免疫反应调节的影响。 ADRB2 受 miR-15a-5p 负调节,抑制 IL-13 诱导的鼻上皮炎症反应。
Allergic rhinitis (AR) is a common hypersensitive disease that troubles patients a lot. Nasal epithelial cells (NECs), as the outmost protection of inhalation, play an important role in AR allergic response. Adrenoceptor beta 2 (ADRB2) is an important gene in inflammatory response, which has become the hot spot for AR development and treatment in recent years. MiR-15a-5p has been proved to be involved in AR immune response as the upstream regulator of ADRB2. Human primary NECs were isolated and stimulated by IL-13. qRT-PCR assay was used to detect the RNA level of target genes. ELISA and Western blotting were applied to detect target protein levels. Luciferase reporter assay and biotin pull-down assay were performed to test molecules interaction. ADRB2 was highly expressed in nasal mucosa of AR patients and was positively correlated with IL-13 stimulation, and knockdown of ADRB2 inhibited IL-13-induced expression of GM-CSF, eotaxin, and MUC5AC in NECs. ADRB2 was directly targeted by miR-15a-5p, and miR-15a-5p inhibited IL-13-induced expression of GM-CSF, eotaxin, and MUC5AC in NECs. ADRB2 mediated the effect of miR-15a-5p on the regulation of nasal epithelial immune responses. ADRB2 is negatively regulated by miR-15a-5p, which inhibits IL-13-induced nasal epithelial inflammatory responses.
E2F1 诱导的长链非编码 RNA LINC00668 的上调可预测胃癌的不良预后,并通过 CKI 的表观遗传沉默促进细胞增殖。
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