Liu Z, Lu X, Zhang X H, Bochner B S, Long X B, Zhang F, Wang H, Cui Y H
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Allergy. 2009 Jan;64(1):149-57. doi: 10.1111/j.1398-9995.2008.01847.x. Epub 2008 Dec 12.
Clara cell 10-kDa protein (CC10) is a multifunction protein with anti-inflammatory and immunomodulatory effects; hence we compared the CC10 expression between chronic rhinosinusitis (CRS) patients with and without nasal polyps (NPs), analyzed its association with disease severity and response to surgery, and explored its regulation via cytokines.
The plasma and tissue CC10 levels were compared between controls and CRS patients with and without NPs by means of quantitative RT-PCR, ELISA, and immunohistochemistry. Computed tomography (CT) scan and endoscopy findings and symptoms were scored. Nasal explant culture was used to explore the effect of TNF-alpha, IL-1beta, IL-4, INF-gamma, and IL-10 on CC10 gene regulation.
Compared with controls, the CC10 expression in sinonasal mucosa was significantly inhibited in both CRS patients with and without NPs. There was a significant further decrease of CC10 expression in patients with NPs and asthma. No difference in CC10 plasma levels was found between controls and patients. CC10 levels inversely correlated with preoperative CT scores, and postoperative endoscopy and symptom scores. TNF-alpha, IL-1beta and IL-4 inhibited, whereas INF-gamma and IL-10 promoted CC10 production in nasal mucosa. A significantly faster decay of CC10 transcripts was seen after IL-1beta treatment. IL-1beta and IL-10 induced thyroid transcription factor-1 expression. INF-gamma increased, whereas IL-4 inhibited hepatocyte nuclear factor-3alpha expression.
CC10 may take part in the pathogenesis of CRS and correlates with disease severity and response to surgery. Different cytokines can regulate CC10 expression in nasal mucosa differentially through modulating mRNA stability and certain transcriptional factors expression.
克拉拉细胞10 kDa蛋白（CC10）是一种具有抗炎和免疫调节作用的多功能蛋白；因此，我们比较了有鼻息肉（NP）和无鼻息肉的慢性鼻-鼻窦炎（CRS）患者之间的CC10表达，分析了其与疾病严重程度及手术反应的相关性，并探讨了细胞因子对其的调控作用。
通过定量逆转录聚合酶链反应（RT-PCR）、酶联免疫吸附测定（ELISA）和免疫组织化学方法，比较对照组与有NP和无NP的CRS患者血浆和组织中的CC10水平。对计算机断层扫描（CT）、内镜检查结果及症状进行评分。采用鼻外植体培养法，探讨肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-4（IL-4）、干扰素-γ（INF-γ）和白细胞介素-10（IL-10）对CC10基因调控的影响。
与对照组相比，有NP和无NP的CRS患者鼻窦黏膜中的CC10表达均显著受到抑制。NP合并哮喘患者的CC10表达进一步显著降低。对照组与患者之间的CC10血浆水平未发现差异。CC10水平与术前CT评分、术后内镜检查及症状评分呈负相关。TNF-α、IL-1β和IL-4抑制鼻黏膜中CC10的产生，而INF-γ和IL-10则促进其产生。IL-1β处理后，CC10转录本的衰减明显加快。IL-1β和IL-10诱导甲状腺转录因子-1表达。INF-γ增加，而IL-4抑制肝细胞核因子-3α表达。
CC10可能参与CRS的发病机制，并与疾病严重程度及手术反应相关。不同的细胞因子可通过调节mRNA稳定性和某些转录因子的表达，对鼻黏膜中CC10的表达产生不同的调控作用。
