The expression of osteopontin and its association with Clara cell 10 kDa protein in allergic rhinitis.
The expression of osteopontin and its association with Clara cell 10 kDa protein in allergic rhinitis.
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DOI：
10.1111/j.1365-2222.2010.03549.x
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Liu Z
中科院分区：
文献类型：
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作者：
Liu Y;Lu X;Yu HJ;Hua XY;Cui YH;Huang SK;Liu Z
骨桥蛋白（OPN）是一种多功能蛋白，最近被认为与过敏性疾病有关。Clara细胞10-kDa蛋白（CC10）是另一种与过敏相关的蛋白，已被认为在炎症性气道疾病中具有抑制作用。目前尚不清楚OPN是否参与变应性鼻炎（AR），也不清楚CC10与OPN在AR中是否存在关联。为了研究OPN在AR中的表达及其与CC10的潜在关联，我们对AR患者鼻黏膜中CC10和OPN的表达进行了研究。采用野生型和cc10敲除小鼠建立AR动物模型。在一些实验中，人重组CC10蛋白在致敏或激发期间给予AR小鼠。通过组织学和实时RT-PCR检测表型变化。通过体外细胞培养，检测CC10对脾单核细胞OPN表达和BEAS-2B细胞OPN诱导的炎性细胞因子表达的直接影响。在AR患者中，OPN表达上调，CC10表达下调，两者表达呈显著负相关。与PBS致敏的对照组小鼠相比，AR小鼠的OPN表达显著增加；与野生型相比，这种增加在cc10基因敲除小鼠中更为突出。在致敏和激发过程中给药CC10可显著改善鼻黏膜th2偏斜炎症和OPN表达。致敏期给药CC10也可降低脾脏OPN的表达。体外研究表明，CC10可直接下调OVA刺激的脾脏单核细胞中OPN的表达，抑制OPN诱导的BEAS-2B细胞中Th2细胞因子和促炎细胞因子的表达。在气道变应性反应的背景下，CC10可以抑制OPN的表达，抑制OPN的Th2促进功能，从而产生CC10的抑制性生物学效应。
Osteopontin (OPN) is a multifunctional protein which has recently been linked to allergic diseases. Clara cell 10-kDa protein (CC10) is another protein linked to allergy, and has been suggested to have an inhibitory role in inflammatory airway diseases. At this time, it is not known whether OPN is involved in allergic rhinitis (AR) or if there is any association between CC10 and OPN in AR. To study the expression of OPN and its potential association with CC10 in AR. The expression of CC10 and OPN in nasal mucosa of AR patients was investigated. AR animal models were established by employing wild-type and CC10-knockout mice. In some experiments, human recombinant CC10 protein was given to AR mice during either sensitization or challenge. The phenotypic changes were examined by histology and real-time RT-PCR. The direct effect of CC10 on OPN expression in spleen mononuclear cells and on OPN-induced inflammatory cytokine expression in BEAS-2B cells was measured through in vitro cell culture. OPN expression was up-regulated, with a concomitant down-regulation of CC10, in AR patients, showing a significant negative correlation between their expression. Compared with control mice sensitized with PBS, OPN expression was significantly increased in AR mice; such increase was more prominent in CC10-knockout mice, compared to wild-type. Administration of CC10 during both sensitization and challenge could markedly ameliorate Th2-skewed inflammation and OPN expression in nasal mucosa. CC10 administration at the sensitization phase could also reduce spleen OPN expression. The in vitro study showed that CC10 directly down-regulated OPN expression in spleen mononuclear cells stimulated with OVA and suppressed OPN-induced expression of Th2 cytokines and proinflammatory cytokines in BEAS-2B cells. In the context of allergic airway responses, CC10 can inhibit OPN expression and suppress the Th2 promoting function of OPN, resulting in CC10’s inhibitory biological effects.