Linke Robert, Pries Ralph, Könnecke Michael, Bruchhage Karl-Ludwig, Böscke Robert, Gebhard Maximilian, Wollenberg Barbara
Department of Oto-Rhino-Laryngology and Facial Plastic Surgery, University of Luebeck, Luebeck, Germany.
Am J Rhinol Allergy. 2015 May-Jun;29(3):182-7. doi: 10.2500/ajra.2015.29.4170.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a recurrent, benign, extensively proliferating disease that is triggered by inflammation. The signaling pathways in sinusitis and the regulation by intracellular signaling peptides and proteins are not fully understood. Signal transducer and activator of transcription (STAT) 5a and STAT5b are two closely related phosphokinases involved in the regulation of diverse cellular functions, including proliferation and apoptosis.
The objective of the study was to investigate the expression, activation, and distribution of STAT5 Transcription factor in CRSwNP.
We studied these transcription factors in tissue samples of nasal polyps and inferior turbinates from a total of 35 patients with CRSwNP and compared them with healthy nasal mucosa. The samples were analyzed by using a DNA microarray, quantitative real-time polymerase chain reaction, a protein array, immunoblot, immunoprecipitation and immunohistochemistry.
We found equivalent overall expression of STAT5a in all tissue types. We observed an increase in the expression of STAT5b protein in both polyps and turbinates of patients with CRSwNP. In addition, STAT5b, but not STAT5a, was activated by phosphorylation in nasal polyps. Phosphorylated STAT5a/b was not detectable in the epithelium of turbinates from either patients with CRSwNP or patients with healthy mucosa, but it was clearly expressed in the epithelium of nasal polyps.
Analysis of these data indicates distinct expression and activation of STAT5a and STAT5b in nasal polyps, particularly the activation of STAT5b. It is possible that STAT5b may contribute to the development of nasal polyps.
伴鼻息肉的慢性鼻-鼻窦炎(CRSwNP)是一种由炎症引发的复发性、良性、广泛增殖性疾病。鼻窦炎中的信号通路以及细胞内信号肽和蛋白质的调控作用尚未完全明确。信号转导和转录激活因子(STAT)5a和STAT5b是两种密切相关的磷酸激酶,参与多种细胞功能的调控,包括增殖和凋亡。
本研究旨在探讨STAT5转录因子在CRSwNP中的表达、激活及分布情况。
我们对35例CRSwNP患者的鼻息肉和下鼻甲组织样本进行研究,并与健康鼻黏膜进行比较。采用DNA微阵列、定量实时聚合酶链反应、蛋白质阵列、免疫印迹、免疫沉淀和免疫组化对样本进行分析。
我们发现STAT5a在所有组织类型中的总体表达相当。我们观察到CRSwNP患者的息肉和鼻甲中STAT5b蛋白表达均增加。此外,鼻息肉中STAT5b而非STAT5a通过磷酸化被激活。在CRSwNP患者或健康黏膜患者的鼻甲上皮中均未检测到磷酸化的STAT5a/b,但在鼻息肉上皮中明显表达。
对这些数据的分析表明,鼻息肉中STAT5a和STAT5b存在不同的表达和激活情况,尤其是STAT5b的激活。STAT5b可能参与鼻息肉的发生发展。