IRAK-M has effects in regulation of lung epithelial inflammation.
IRAK-M has effects in regulation of lung epithelial inflammation.
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DOI：
10.1186/s12931-023-02406-5
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发表时间：
2023-04-07
影响因子：
5.8
通讯作者：
中科院分区：
文献类型：
--
作者：
上皮屏障通过影响免疫反应，对哮喘的发生发展起着重要作用。Toll样受体途径的气道表达-IL-1受体相关激酶(IRAK)-M通过影响巨噬细胞和树突状细胞的活性或T细胞分化参与了气道炎症的免疫调节。IRAK-M是否对刺激后的呼吸道上皮细胞的细胞免疫有影响尚不清楚。我们在BEAS-2B和A549细胞中模拟了IL-1β、肿瘤坏死因子-α、IL-33和屋尘螨诱导的细胞炎症。通过细胞因子的产生和途径的激活来反映IRAK-M siRNA敲除对上皮免疫的影响。对哮喘患者进行了IRAK-M SNP rs1624395基因分型和血清CXCL10水平检测。炎症刺激可显著诱导BEAS-2B和A549细胞表达IRAK-M。IRAK-M基因敲除增加了肺上皮细胞因子和趋化因子的产生，包括IL-6、IL-8、CXCL10和CXCL11，在mRNA和蛋白水平上都是如此。在刺激下，IRAK-M沉默导致肺上皮细胞JNK和p38MAPK的过度激活。拮抗JNK或p38MAPK可抑制IRAK-M沉默的肺上皮细胞分泌CXCL10的增加。携带G/G基因的哮喘患者血清CXCL10水平明显高于携带A/A纯合子的患者。提示IRAK-M可能通过JNK和p38MAPK途径影响肺上皮细胞分泌CXCL10。IRAK-M的调节可能为从疾病的起源认识哮喘的发病机制提供了新的视角。网上版载有补充材料，可在10.1186/s12931-023-02406-5查阅。
Epithelial barrier is important for asthma development by shaping immune responses. Airway expressing-IL-1 receptor-associated kinase (IRAK)-M of Toll-like receptor pathway was involved in immunoregulation of airway inflammation through influencing activities of macrophages and dendritic cells or T cell differentiation. Whether IRAK-M has effect on cellular immunity in airway epithelial cells upon stimulation remains unclear. We modeled cellular inflammation induced by IL-1β, TNF-α, IL-33, and house dust mite (HDM) in BEAS-2B and A549 cells. Cytokine production and pathway activation were used to reflect the effects of IRAK-M siRNA knockdown on epithelial immunity. Genotyping an asthma-susceptible IRAK-M SNP rs1624395 and measurement of serum CXCL10 levels were performed in asthma patients. IRAK-M expression was significantly induced in BEAS-2B and A549 cells after inflammatory stimulation. IRAK-M knockdown increased the lung epithelial production of cytokines and chemokines, including IL-6, IL-8, CXCL10, and CXCL11, at both mRNA and protein levels. Upon stimulation, IRAK-M silencing led to overactivation of JNK and p38 MAPK in lung epithelial cells. While antagonizing JNK or p38 MAPK inhibited increased secretion of CXCL10 in IRAK-M silenced-lung epithelium. Asthma patients carrying G/G genotypes had significantly higher levels of serum CXCL10 than those carrying homozygote A/A. Our findings suggested that IRAK-M has effect on lung epithelial inflammation with an influence on epithelial secretion of CXCL10 partly mediated through JNK and p38 MAPK pathways. IRAK-M modulation might indicate a new insight into asthma pathogenesis from disease origin. The online version contains supplementary material available at 10.1186/s12931-023-02406-5.
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DOI：
10.1016/j.jaci.2011.10.043
发表时间：
2012-03
期刊：
The Journal of allergy and clinical immunology
影响因子：
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作者：
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DOI：
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发表时间：
2011-08-01
影响因子：
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作者：
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影响因子：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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影响因子：
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