Eosinophil-epithelial cell interactions stimulate the production of MUC5AC mucin and profibrotic cytokines involved in airway tissue remodeling

嗜酸性粒细胞-上皮细胞相互作用刺激 MUC5AC 粘蛋白和促纤维化细胞因子的产生，参与气道组织重塑

• 批准号: 23592509
• 负责人: SHIMIZU TAKESHI
• 金额: $ 3.41万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592509/
• 关键词: 好酸球; 鼻副鼻腔炎; 粘液産生; 鼻茸; 上皮細胞; 組織リモデリング; ＥＧＦ受容体; MUC5AC; 鼻茸形成; ＭＵＣ５ＡＣ; 気道上皮細胞; ムチン; EGFR; 慢性副鼻腔炎; ADAM; TGF-alpha; amphiregulin

To elucidate the role of eosinophils in tissue remodeling of chronic rhinosinusitis, eosinophil-epithelial interactions were examined by the co-culture of airway epithelial (NCI-H292) cells with the eosinophilic cell line EoL-1 or with human blood eosinophils.Eosinophil-epithelial interactions stimulated the secretion of MUC5AC, PDGF, VEGF, TGF-beta and IL-8 in culture supernatants. The EGFR tyrosine kinase inhibitor AG1478 inhibited the co-culture-induced secretion of MUC5AC, PDGF, VEGF, and IL-8. Neutralizing antibodies directed against TGF-alpha or amphiregulin and pan-metalloprotease inhibitor GM6001 inhibited the co-culture-induced secretion of MUC5AC and amphiregulin from the co-cultured NCI-H292 cells. These results indicate that eosinophil-epithelial interactions stimulate tissue remodeling induced by MUC5AC mucin, PDGF and VEGF, probably mediated by metalloprotease-dependent EGFR transactivation via amphiregulin and TGF-alpha released from the epithelial cells.

为了阐明嗜酸性粒细胞在慢性鼻窦炎组织重塑中的作用，通过将气道上皮细胞（NCI-H292）与嗜酸性细胞系EoL-1或与人血嗜酸性粒细胞共培养来检测嗜酸性粒细胞与上皮细胞的相互作用，嗜酸性粒细胞与上皮细胞的相互作用刺激培养上清液中MUC 5AC、PDGF、VEGF、TGF-β和IL-8的分泌。EGFR酪氨酸激酶抑制剂AG 1478抑制共培养诱导的MUC 5AC、PDGF、VEGF和IL-8的分泌。针对TGF-α或双调蛋白的中和抗体和泛金属蛋白酶抑制剂GM 6001抑制共培养物诱导的MUC 5AC和双调蛋白从共培养的NCI-H292细胞的分泌。这些结果表明，嗜酸性粒细胞-上皮细胞相互作用刺激由MUC 5AC粘蛋白、PDGF和VEGF诱导的组织重塑，这可能是由上皮细胞释放的双调蛋白和TGF-α介导的金属蛋白酶依赖性EGFR反式激活介导的。

项目成果

Role of eosinophils in tissue remodeling of chronic rhinosinusitis

嗜酸性粒细胞在慢性鼻窦炎组织重塑中的作用

• 发表时间: 2013
• 作者: Shimizu T;Shimizu S
• 通讯作者: Shimizu S

気道上皮細胞と好酸球の相互作用による粘液・サイトカイン分泌

由于气道上皮细胞和嗜酸性粒细胞之间的相互作用而分泌粘液和细胞因子

• 发表时间: 2012
• 作者: 清水志乃;神前英明;清水猛史
• 通讯作者: 清水猛史

粘液・サイトカイニン分泌における好酸球と上皮細胞の交互作用

粘液中嗜酸性粒细胞和上皮细胞之间的相互作用和细胞分裂素分泌

• 发表时间: 2012
• 作者: 清水志乃;清水猛史
• 通讯作者: 清水猛史

Role of coagulation factors and eosinophils in the pathogenesis of mucus hypersecretion in eosinophil-associated chronic rhinosinusitis

凝血因子和嗜酸性粒细胞在嗜酸性粒细胞相关慢性鼻窦炎粘液分泌过多发病机制中的作用

• 发表时间: 2013
• 作者: 3.Sakashita T;Homma A;Oridate N;Suzuki S;Hatakeyama H;Kano S;Mizumachi T;Onimaru R;Tsuchiya K;Yasuda K;Shirato H;Fukuda S;Shimizu T
• 通讯作者: Shimizu T

Tsissue remodeling of eosinophil-associated chronic rhinosinusitis

嗜酸性粒细胞相关的慢性鼻窦炎的组织重塑

• 发表时间: 2013
• 作者: Fertig EJ;Ren Q;Cheng H;Hatakeyama H;Dicker AP;Rodeck U;Considine M;Ochs MF;Chung CH;Shimizu T
• 通讯作者: Shimizu T