Asthmatic airway biopsy specimens are more likely to express the IL-4 alternative splice variant IL-4δ2
Asthmatic airway biopsy specimens are more likely to express the IL-4 alternative splice variant IL-4δ2
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DOI：
10.1016/s0091-6749(99)70078-3
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发表时间：
1999-11-01
影响因子：
14.2
通讯作者：
Walters, EH
中科院分区：
文献类型：
--
作者：
Glare, EM;Divjak, W;Walters, EH
背景：人IL-4基因已被证明表达选择性剪接信使（m）RNA IL-4 δ 2。IL-4 delta 2是一种缺失了第2外显子的完整序列的IL-4受体拮抗剂，目的：首次对呼吸道组织中IL-4和IL-4 delta 2 mRNA进行区分。在IL 4基因可变剪接点两侧设计引物，建立了一种新的竞争PCR检测方法，结果：IL-4和IL-4 delta 2在4例鼻息肉组织中均有不同程度的表达。对照组间支气管内活检标本IL-4 mRNA表达无差异（中位数，2.8 × 10（2）拷贝/μ g RNA;范围，0-3.7 × 10（3）拷贝/μ g RNA）和哮喘受试者（中位数，1.4 × 10（2）拷贝/μ g RNA;范围，0-4.7 × 10（2）拷贝/μ g RNA），然而，哮喘组（6/9）比对照组（1/7）表达IL-4 δ 2（P = 0.036），IL-4变体的表达不受特应性状态的影响。鉴于IL-4 δ 2是IL-4受体拮抗剂，这些结果表明，在评估IL-4基因表达时，能够区分IL-4 δ 2和IL-4是至关重要的。稳定期哮喘患者IL-4 delta 2表达增加提示IL-4和IL-4 delta 2的平衡可能调节哮喘炎症。
Background: The human IL4 gene, has been shown to express the alternatively spliced messenger (m)RNA IL-4 delta 2. IL-4 delta 2 is missing the entire sequence from exon 2 and has been identified as an IL-4 receptor antagonist.Objective: We sought to distinguish IL-4 and IL-4 delta 2 mRNA in respiratory tract tissue for the first time.Methods: A novel competitive PCR assay was established with primers designed on either side of the alternative splice junction of the IL4 gene, allowing the simultaneous quantitation of both IL-4 and IL-4 delta 2 mRNA from one reaction.Results: IL-4 and IL-4 delta 2 were differentially expressed in 4 nasal polyps. No difference was seen in endobronchial biopsy specimens for IL-4 mRNA expression between control subjects (median, 2.8 x 10(2) copies/mu g RNA; range, 0-3.7 x 10(3) copies/mu g RNA) and asthmatic subjects (median, 1.4 x 10(2) copies/mu g RNA; range, 0-4.7 x 10(2) copies/mu g RNA), However, significantly more asthmatic subjects (6 of 9) than control subjects (1 of 7) expressed IL-4 delta 2 (P = .036), Expression of IL-4 variants was unaffected by atopic status.Conclusions: Given that IL-4 delta 2 is an IL-4 receptor antagonist, these results indicate that it is crucial to be able to distinguish IL-4 delta 2 from IL-4 when assessing IL4 gene expression. Increased expression of IL-4 delta 2 in stable asthmatic subjects suggests that the balance of IL-4 and IL-4 delta 2 may modulate asthmatic inflammation.