IL-17A在食管腺癌中的表达及其对NF-κB/COX-2信号轴的调控作用OACSTPCD
Expression of IL-17A in esophageal adenocarcinoma and its regulatory effect on NF-κB/COX-2 signaling axis
目的 探讨白细胞介素17A(IL-17A)在食管腺癌中的表达情况及其通过核转录因子κB(NF-κB)信号通路对环氧合酶-2(COX-2)的调控作用及机制.方法 收集10例食管腺癌组织、癌旁组织和血清,同时收集10例做胃镜检查的健康体检者的食管上皮组织和血清,免疫组化法检测组织中IL-17A和COX-2蛋白的表达,real time-PCR法检测癌组织和癌旁组织中IL-17A mRNA和Th17细胞的特异性转录因子维甲酸相关孤儿核受体c(RORc)mRNA的表达,ELISA法检测食管腺癌患者和健康对照者血清中IL-17A的含量.选取对数生长期的人食管腺癌OE19细胞,分为对照组、IL-17A(100 ng/mL)组和IL-17A(100 ng/mL)+PDTC(100 µmol/L,NF-κB信号通路抑制剂吡咯烷二硫代甲酸铵)组,Western blot法检测OE19细胞中p50、p65、p-IKB-α和COX-2蛋白的表达水平.结果 食管腺癌组织中IL-17A阳性染色细胞数高于癌旁组织;相较于癌旁组织,食管腺癌组织中IL-17A和RORc mRNA水平增多(P＜0.05).与健康对照者相比,食管腺癌患者血清中IL-17A的含量明显升高(P＜0.05).与正常食管上皮组织比较,食管腺癌组织中 COX-2蛋白阳性染色面积更大更深.与对照组相比,IL-17A组OE19细胞中p-IκB-α和COX-2蛋白的表达量明显增加(P＜0.05);与IL-17A组相比较,IL-17A+PDTC组细胞中p-IκB-α和COX-2蛋白的表达量明显降低(P＜0.05).结论 IL-17A表达在食管腺癌患者组织和血清中均增加.在食管腺癌OE19细胞中,IL-17A可能通过激活NF-κB信号通路上调COX-2的表达量.
Objective To explore the expression of interleukin 17A(IL-17A)in esophageal adenocarcinoma and its role and mecha-nism in the regulation of cyclooxygenase-2(COX-2)protein through the nuclear transcription factor κB(NF-κB)signaling pathway.Methods The specimens of esophageal adenocarcinoma,paracancerous tissues and serum were collected from ten patients with esopha-geal adenocarcinoma.At the same time,normal esophageal epithelial tissues and serum were collected from ten healthy subjects undergoing gastroscopy.Expressions of IL-17A and COX-2 proteins were detected in tissues by immunohistochemical assay.IL-17A mRNA and retinoic acid receptor related orphan c(RORc)mRNA,a specific transcription factor of Th17 cells,were detected in cancerous tissues and paracancerous tissues by real time-PCR method.The serum levels of IL-17A were measured in esophageal adeno-carcinoma patients and healthy controls by ELISA method.Human esophageal adenocarcinoma OE19 cells in logarithmic growth phase were divided into control group,IL-17A(100 ng/mL)group and IL-17A(100 ng/mL)+PDTC(100 μmol/L,NF-κB signaling pathway inhibitor pyrrolidine di thiocarbamate)group,and the expressions of p50,p65,p-IκB-α,and COX-2 proteins were detected by Western blotting in OE19 cells.Results The number of IL-17A-positive cells was higher in cancer tissues than in paracancerous tissues.The levels of IL-17A mRNA and RORc mRNA were increased in esophageal adenocarcinoma tissues compared to paracancerous tissues(P＜0.05).Serum level of IL-17A was significantly higher in patients with esophageal adenocarcinoma than in healthy controls(P＜0.05).Compared with normal esophageal epithelial tissues,there was a larger and deeper positive staining area of COX-2 protein in esophageal adenocarcinoma tissues.The expressions of p-IκB-α and COX-2 proteins in OE19 cells in IL-17A group was significantly increased compared with control group(P＜0.05),and the expressions of p-IKB-α and COX-2 proteins in OE19 cells in IL-17A+PDTC group were significantly decreased compared with IL-17A group(P＜0.05).Conclusion IL-17A expression is increased in both tissues and serum of patients with esophageal adenocarcinoma.IL-17A could upregulate the expression of COX-2 in OE19 cells by activating the NF-κB signaling pathway.
冯诚;刘冬;张军;张蓉;吴菁;程妍
西安交通大学第二附属医院麻醉科,西安 710004西安交通大学第二附属医院消化内科陕西省人民医院消化内科
临床医学
食管腺癌白细胞介素17A环氧合酶-2NF-κB信号通路炎症OE19细胞
esophageal adenocarcinomainterleukin 17 ACOX-2nuclear transcription factor κBinflammationOE19 cells
《山西医科大学学报》 2024 (007)
813-819 / 7
国家卫生部临床重点项目(2007353);国家自然科学基金资助项目(81700474)
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