Divison of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
Department of ENT Diseases, Karolinska University Hospital, Stockholm, Sweden.
Sci Rep. 2018 Jan 24;8(1):1561. doi: 10.1038/s41598-018-19955-1.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a widespread disease causing obstruction of the nasal cavity. Its cause remains unclear. The transforming growth-factor beta (TGF-β) superfamily and their receptors, termed Activin receptor-like kinases (ALKs), have recently been suggested to play a role in local airway inflammation, but have so far not been evaluated in human nasal epithelial cells (HNECs) from CRSwNP patients. We demonstrated that ALK1-7 were expressed in the nasal polyp epithelium, and the expression of ALK1-6 was markedly elevated in polyps compared to nasal mucosa from healthy controls. Stimulation with the ALK ligand TGF-β1 decreased Ki67 expression in HNECs from CRSwNP patients, not evident in controls. Likewise, TGF-β1, Activin A and Activin B, all ALK ligands, decreased IL-8 release and Activin A and Activin B reduced ICAM1 expression on HNECs from CRSwNP patients, not seen in controls. Pre-stimulation with TGF-β1, Activin A, BMP4 and Activin B attenuated a TNF-α-induced ICAM1 upregulation on HNECs of CRSwNP. No effect was evident in controls. In conclusion, an increased expression of ALK1-6 was found on polyp epithelial cells and ligand stimulation appeared to reduce proliferation and local inflammation in polyps.
慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）是一种广泛存在的疾病，可导致鼻腔阻塞。其病因尚不清楚。转化生长因子-β（TGF-β）超家族及其受体，称为激活素受体样激酶（ALKs），最近被认为在局部气道炎症中发挥作用，但迄今为止尚未在 CRSwNP 患者的人鼻腔上皮细胞（HNECs）中进行评估。我们证明 ALK1-7 在鼻息肉上皮中表达，并且与健康对照组的鼻黏膜相比，息肉中 ALK1-6 的表达明显升高。ALK 配体 TGF-β1 的刺激可降低 CRSwNP 患者 HNECs 中的 Ki67 表达，但在对照组中不明显。同样，ALK 配体 TGF-β1、激活素 A 和激活素 B 均降低 CRSwNP 患者 HNECs 中 IL-8 的释放，并且激活素 A 和激活素 B 降低 CRSwNP 患者 HNECs 中 ICAM1 的表达，但在对照组中未见。在 TNF-α 诱导的 ICAM1 上调之前用 TGF-β1、激活素 A、BMP4 和激活素 B 预处理可减弱 CRSwNP 患者 HNECs 中的 ICAM1 上调。在对照组中未见明显效果。总之，在息肉上皮细胞上发现了 ALK1-6 的表达增加，并且配体刺激似乎可减少息肉中的增殖和局部炎症。
