CD38 in the pathogenesis of allergic airway disease: Potential therapeutic targets.
CD38 in the pathogenesis of allergic airway disease: Potential therapeutic targets.
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DOI：
10.1016/j.pharmthera.2016.12.002
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发表时间：
2017-04
影响因子：
13.5
通讯作者：
Kannan MS
中科院分区：
文献类型：
--
作者：
Deshpande DA;Guedes AGP;Lund FE;Subramanian S;Walseth TF;Kannan MS
CD38是一种胞外酶，催化β-烟酰胺腺嘌呤二核苷酸(β-NAD)转化为环腺苷二磷核糖(CADPR)和腺苷二磷酸核糖(ADPR)，并将其转化为烟酸腺嘌呤二核苷酸磷酸(NAADP)和腺苷二磷酸核糖-2‘-磷酸(ADPR-P)。NAD和NADP的代谢产物在不同细胞类型的钙信号转导中发挥作用，包括气道平滑肌(ASM)细胞。在ASM细胞中，炎性细胞因子增强CD38的表达，并在哮喘患者的细胞中达到更大的幅度，表明哮喘患者ASM中产生cADPR和ADPR的能力更强。与野生型小鼠相比，CD38缺陷小鼠在过敏原致敏和激发后对吸入乙酰甲胆碱的呼吸道反应性减弱，表明其在哮喘中的潜在作用。CD38在ASM细胞中的表达是通过丝裂原激活的蛋白激酶、PI3K的特定亚型、转录因子NF-κB和AP-1以及由microRNAs转录后实现的。这篇综述将集中于CD38在ASM细胞内钙调节中的作用，在过敏性气道炎症小鼠模型中对气道炎症和气道高反应性的贡献，转录和转录后调控表达的机制，并概述抑制其表达和活性的方法。
CD38 is an ectoenzyme that catalyzes the conversion of β-nicotinamide adenine dinucleotide (β-NAD) to cyclic adenosine diphosphoribose (cADPR) and adenosine diphosphoribose (ADPR) and NADP to nicotinic acid adenine dinucleotide phosphate (NAADP) and adenosine diphosphoribose-2’-phosphate (ADPR-P). The metabolites of NAD and NADP have roles in calcium signaling in different cell types including airway smooth muscle (ASM) cells. In ASM cells, inflammatory cytokines augment CD38 expression and to a greater magnitude in cells from asthmatics, indicating a greater capacity for the generation of cADPR and ADPR in ASM from asthmatics. CD38 deficient mice develop attenuated airway responsiveness to inhaled methacholine following allergen sensitization and challenge compared to wild-type mice indicating its potential role in asthma. Regulation of CD38 expression in ASM cells is achieved by mitogen activated protein kinases, specific isoforms of PI3 kinases, the transcription factors NF-κB and AP-1, and post-transcriptionally by microRNAs. This review will focus on the role of CD38 in intracellular calcium regulation in ASM, contribution to airway inflammation and airway hyperresponsiveness in mouse models of allergic airway inflammation, the transcriptional and post-transcriptional mechanisms of regulation of expression, and outline approaches to inhibit its expression and activity.