Evidence for diminished levels of epithelial psoriasin and calprotectin in chronic rhinosinusitis.

Evidence for diminished levels of epithelial psoriasin and calprotectin in chronic rhinosinusitis.
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DOI:
10.1016/j.jaci.2009.11.045
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发表时间:
2010-03
影响因子:
14.2
通讯作者:
Schleimer, Robert P.
Schleimer, Robert P.
中科院分区:
医学1区
文献类型:
--
作者:
Tieu, David D.;Peters, Anju T.;Carter, Roderick T.;Suh, Lydia;Conley, David B.;Chandra, Rakesh;Norton, James;Grammer, Leslie C.;Harris, Kathleen E.;Kato, Atsushi;Kern, Robert C.;Schleimer, Robert P.

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据报道,在慢性鼻-鼻窦炎(CRS)中,S100A7(Psoriasin)和S100A8/A9(钙保护素)的mRNA在上皮中的表达降低。目的:探讨慢性阻塞性肺疾病患者鼻腔中S100蛋白的表达是否也发生改变。采用免疫组织化学方法检测CRS患者鼻息肉组织和钩突组织中S100蛋白的表达,并用ELISA法检测CRS患者鼻腔灌洗液和鼻窦组织提取液中S100蛋白的水平。与对照组相比,两组CRS患者鼻腔灌洗液中S100蛋白的表达水平均降低(p<0.05)。同样,免疫组织化学评估这些蛋白的组织表达显示明显减少,主要是在上皮衬里。有趣的是,尽管灌洗液中钙保护素的水平较低,但鼻息肉组织中钙保护素的水平却增加了。鼻腔组织中钙保护素的水平与中性粒细胞的水平相关,通过中性粒细胞弹性酶的定量来评估。一些S100蛋白存在于基因的表皮分化复合体中,已被证明在维持屏障功能和形成抗菌屏障方面发挥作用。我们发现CRS患者上皮细胞中S100蛋白的表达水平显著降低,这可能导致先天性免疫反应和屏障功能的减弱。鼻息肉组织中钙保护素水平的升高可能反映了中性粒细胞的募集和代偿机制。未来的研究将是重要的,以确定S100蛋白水平的降低是否会导致上呼吸道和鼻窦的抗菌反应降低,以及这种减少是否在CRS的发病机制和感染性疾病的易感性中起到病因学作用。
Decreased epithelial expression of mRNA for S100A7 (Psoriasin) and S100A8/A9 (Calprotectin) have been reported in chronic rhinosinusitis (CRS). To assess whether the expression of S100 proteins is also altered in the sinonasal cavity of patients with CRS. We determined levels of S100 proteins in nasal lavage and sinonasal tissue extracts from CRS patients using ELISA and immunohistochemical analysis of nasal polyp tissue from CRSwNP patients and uncinate tissue from all three groups. Expression levels of S100 proteins were decreased compared to control subjects in nasal lavage fluids from both CRS groups (p < 0.05). Similarly, tissue expression of these proteins assessed by immunohistochemistry demonstrated clear reductions primarily in the epithelial lining. Interestingly, levels of Calprotectin were increased in nasal polyp tissue despite lower levels in lavage fluid. Levels of Calprotectin in nasal tissues were correlated with levels of neutrophils as assessed by quantification of neutrophil elastase. Several S100 proteins are in the epidermal differentiation complex of genes and have been demonstrated to play a role in maintenance of barrier function and formation of an antimicrobial shield. We demonstrate significantly decreased levels of expression of S100 proteins in epithelium of CRS patients, which may lead to diminished innate immune response and barrier function. Increased levels of Calprotectin in nasal polyp tissue may reflect neutrophil recruitment and a compensatory mechanism. Future studies will be important to determine whether reduced levels of S100 proteins lead to decreased antimicrobial responses in the upper airways and sinuses and whether this reduction plays an etiologic role in CRS pathogenesis and susceptibility to infectious disease.
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