Inflammation-mediated upregulation of centrosomal protein 110, a negative modulator of ciliogenesis, in patients with chronic rhinosinusitis

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• 作者：Yinyan Lai MD^a ;   ; ^b ; Bei Chen MD^b ; Jianbo Shi MD^a ; James N. Palmer MD^b ;   ; ^c ; David W. Kennedy MD^b ; Noam A. Cohen MD ; PhD^b ;   ; ^c ;   ; ^{cohenn@uphs.upenn.edu}
• 关键词：Chronic rhinosinusitis ; ciliated epithelial cell ; ciliogenesis ; cytokine ; inflammation ; centrosomal protein 110
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：128
• 期：6
• 页码：1207-1215.e1
• 全文大小：1269 K

文摘

Background

Sinonasal mucosa in patients with chronic rhinosinusitis (CRS) is often devoid of motile cilia. This defect is presumed to result from prolonged inflammation, infection, or both. However, the mechanism underlying this observation is unknown. Recently, centrosomal protein 110 (Cp110) was shown to prevent the terminal step in ciliary maturation (ie, elongation), suggesting that Cp110 might be involved in pathological states in which ciliation is abnormal.

Objectives

First, we sought to investigate the expression of Cp110 in sinonasal mucosa from patients with CRS and control subjects. Second, we sought to determine the extent that inflammatory cytokines modulate Cp110 expression and ciliary maturation in?vitro.

Methods

Sinonasal mucosal specimens from patients with and without CRS were analyzed for Cp110 mRNA and protein expression. Furthermore, human and murine nasal respiratory epithelial cultures were used to investigate Cp110 expression under normal growth conditions and in the presence of exogenous proinflammatory cytokines.

Results

Increased Cp110 mRNA and protein expression was found in sinonasal mucosal specimens from patients with CRS compared with that seen in control specimens. During ciliogenesis in?vitro, the expression of Cp110 gradually decreased in cultures derived from patients without CRS but remained increased in cultures derived from patients with CRS. Furthermore, cultures grown in the presence of proinflammatory cytokines demonstrated increased levels of Cp110 expression with concomitant inhibition of ciliogenesis.

Conclusion

Increased Cp110 expression in mucosa from patients with CRS might contribute to the poor ciliation observed in patients with CRS. Exogenous cytokine exposure maintains increased levels of Cp110 expression. Regulation of Cp110 expression by inflammation warrants additional investigation because it might offer a novel target in the management of respiratory tract diseases.