IL-6 Contributes to the TGF-β1-Mediated Epithelial to Mesenchymal Transition in Human Salivary Gland Epithelial Cells

Arch Immunol Ther Exp (Warsz). 2020 Sep 10;68(5):27. doi: 10.1007/s00005-020-00591-5.


To determine the role of IL-6 in bringing about the EMT, in SGEC obtained from healthy subjects. Human salivary gland (SGs) epithelial cells (SGEC) from primary Sjögren's syndrome (pSS) are able to synthesize interleukin (IL)-6, which is a critical mediator of the SGs modifications in response to chronic inflammation. Recently, a hypothetical link between epithelial-mesenchymal transition (EMT)-dependent salivary gland fibrosis and chronic inflammatory conditions has been suggested for pSS; the present study was conducted to evaluate this link. Primary cultures of human SGEC from salivary mucoceles were stimulated with increasing concentrations of IL-6 for 24-72 h. Microscopy, RT-PCR, Real-time PCR, immunoblotting and flow cytometry were used to detect morphological changes, mRNA and protein expression of the EMT markers E-Cadherin, Vimentin and Collagen type I following IL-6 stimulation. The data collected demonstrate that IL-6 can induce SGEC to undergo a morphological and phenotypical transition to a mesenchymal phenotype, in a dose-dependent manner. Decreased mRNA levels of E-Cadherin accompanied by higher mRNA levels of Vimentin and Collagen type I were observed in the IL-6-treated cells compared to control cells (all p < 0.05). This was confirmed at the protein level, demonstrating the decreased E-Cadherin expression, while Vimentin and Collagen type I expression was increased in IL-6-treated SGEC compared to controls (all p < 0.05). The results obtained corroborate the hypothesis that dysregulated cytokines IL-6 may contribute to the EMT-dependent fibrosis, offering a more complete understanding of the role of the EMT during SGs fibrosis in pSS.

Keywords: EMT; IL-6; Salivary gland; Sjögren’s syndrome; TGF-β1.

MeSH terms

  • Cadherins / metabolism
  • Cells, Cultured
  • Collagen Type I / metabolism
  • Down-Regulation
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / genetics
  • Fibrosis / genetics
  • Fibrosis / metabolism*
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-6 / pharmacology*
  • Salivary Glands / cytology
  • Salivary Glands / drug effects
  • Salivary Glands / metabolism*
  • Sjogren's Syndrome / genetics
  • Sjogren's Syndrome / metabolism*
  • Transforming Growth Factor beta1 / metabolism*
  • Up-Regulation
  • Vimentin / metabolism


  • Cadherins
  • Collagen Type I
  • IL6 protein, human
  • Interleukin-6
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Vimentin