Cold-inducible RNA-binding protein contributes to tissue remodeling in chronic rhinosinusitis with nasal polyps
Cold-inducible RNA-binding protein contributes to tissue remodeling in chronic rhinosinusitis with nasal polyps
复制标题
冷诱导RNA结合蛋白有助于慢性鼻窦炎伴鼻息肉的组织重塑
作者：
Shi Li-Li;Ma Jin;Deng Yi-Ke;Chen Cai-Ling;Wang Heng;Cao Ping-Ping;Long Xiao-Bo;Zeng Ming;Liu Zheng
冷诱导RNA结合蛋白（Cold-inducible RNA-binding protein，CIRP）是一种新发现的损伤相关分子模式分子。除了促进炎症和人类疾病外，其作用还知之甚少。本研究旨在探讨CIRP在慢性鼻窦炎伴鼻息肉（CRSwNP）中的作用。方法采用免疫组化、定量RT-PCR和ELISA方法检测CIRP和基质金属蛋白酶（MMPs）在慢性鼻窦炎伴鼻息肉（CRSwNP）中的表达。人鼻上皮细胞（HNECs）和THP-1细胞，一个人单核细胞/巨噬细胞系，培养，探讨调节CIRP的表达和MMP expression.ResultsCytoplasmic CIRP在鼻上皮细胞和CD 68+巨噬细胞在鼻窦组织中的表达，和CIRP水平在鼻分泌物中均显着增加与嗜酸性粒细胞和noneosinophilic CRSwNP患者相比，在对照组。IL-4、IL-13、IL-10、IL-17 A、TNF-α、屋尘螨1型和脂多糖诱导从THP-1细胞分化的HNEC和巨噬细胞产生和分泌CIRP。CIRP促进HNEC、从THP-1细胞分化的巨噬细胞和息肉组织产生MMP 2、MMP 7、MMP 9、MMP 12和血管内皮生长因子A（VEGF-A），这受到Toll样受体4阻断抗体的抑制，但不受晚期糖基化终产物的抑制。CRSwNP患者鼻分泌物中的CIRP水平与组织中MMP和VEGF-A的表达相关。结论鼻上皮细胞和巨噬细胞CIRP的产生和释放上调可能通过诱导上皮细胞和巨噬细胞产生MMP和VEGF-A而导致嗜酸性和非嗜酸性CRSwNP的水肿形成。
BackgroundCold‐inducible RNA‐binding protein (CIRP) is a newly identified damage‐associated molecular pattern molecule. Its roles beyond promoting inflammation and in human diseases are poorly understood. This study aimed to investigate the involvement of CIRP in chronic rhinosinusitis with nasal polyps (CRSwNP).MethodsImmunohistochemistry, quantitative RT‐PCR, and ELISA were used to detect the expression of CIRP and matrix metalloproteinases (MMPs) in sinonasal mucosal samples and nasal secretions. Human nasal epithelial cells (HNECs) and THP‐1 cells, a human monocytic/macrophage cell line, were cultured to explore the regulation of CIRP expression and MMP expression.ResultsCytoplasmic CIRP expression in nasal epithelial cells and CD68+macrophages in sinonasal tissues, and CIRP levels in nasal secretions were significantly increased in both patients with eosinophilic and noneosinophilic CRSwNP as compared to those in control subjects. IL‐4, IL‐13, IL‐10, IL‐17A, TNF‐α,Dermatophagoides pteronyssinusgroup 1, and lipopolysaccharide induced the production and secretion of CIRP from HNECs and macrophages differentiated from THP‐1 cells. CIRP promoted MMP2, MMP7, MMP9, MMP12, and vascular endothelial growth factor A (VEGF‐A) production from HNECs, macrophages differentiated from THP‐1 cells, and polyp tissues, which was inhibited by the blocking antibody for Toll‐like receptor 4, but not advanced glycation end products. The expression of MMPs and VEGF‐A in tissues correlated with CIRP levels in nasal secretions in patients with CRSwNP.ConclusionsThe upregulated production and release of CIRP from nasal epithelial cells and macrophages may contribute to the edema formation in both eosinophilic and noneosinophilic CRSwNP by inducing MMP and VEGF‐A production from epithelial cells and macrophages.