Interleukin-17 (IL-17) is a pleiotropic cytokine that plays a primary role in triggering epithelial–mesenchymal transition (EMT) in many chronic inflammatory diseases. EMT plays a critical role in the progression of salivary gland (SG) fibrosis in primary Sjögren’s syndrome (pSS). This study focused on the activation of the canonical TGF-β1/Smad2/3 and noncanonical TGF-β1/Erk1/2 pathways in IL-17-dependent TGFβ1-induced EMT in human SG epithelial cells (SGEC) derived from healthy subjects. The expression of phosphorylated Smad2/3 and Erk1/2 during IL-17 treatment-stimulated EMT was evaluated in healthy SGEC. Cotreatment with IL-17 and specific TGFβ receptor type I kinase inhibitor SB431542, or Erk 1/2 inhibitor U0126, abrogates the corresponding morphological changes and EMT phenotypic markers expression in healthy SGEC. Interestingly, inhibition of canonical TGFβ1/Smad2/3 signal transduction had no effect on activation of the noncanonical TGFβ1/Erk1/2/EMT pathway, suggesting that the two pathways act independently in activating IL-17-dependent EMT in SGEC.

白细胞介素 17 (IL-17) 是一种多效性细胞因子，在许多慢性炎症性疾病中在触发上皮-间质转化 (EMT) 中起主要作用。EMT 在原发性干燥综合征 (pSS) 唾液腺 (SG) 纤维化的进展中起着关键作用。本研究重点关注源自健康受试者的人 SG 上皮细胞 (SGEC) 中 IL-17 依赖性 TGFβ1 诱导的 EMT 中典型 TGF-β1/Smad2/3 和非典型 TGF-β1/Erk1/2 通路的激活。在健康的 SGEC 中评估了 IL-17 治疗刺激的 EMT 期间磷酸化 Smad2/3 和 Erk1/2 的表达。与 IL-17 和特异性 TGFβ 受体 I 型激酶抑制剂 SB431542 或 Erk 1/2 抑制剂 U0126 共同治疗可消除健康 SGEC 中相应的形态学变化和 EMT 表型标志物表达。有趣的是，