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

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

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.

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Acknowledgement

We are grateful to M.V.C. Pragnell, B.A., a professional scientific text editor, for critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Basic Medical Sciences, Neurosciences and Sensory Organs (SMBNOS), Section of Human Anatomy and Histology, University of Bari “Aldo Moro”, piazza Giulio Cesare 1, 70124, Bari, Italy

    Margherita Sisto, Roberto Tamma, Domenico Ribatti & Sabrina Lisi

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  1. Margherita Sisto
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  2. Roberto Tamma
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  3. Domenico Ribatti
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  4. Sabrina Lisi
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Correspondence to Margherita Sisto.

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Sisto, M., Tamma, R., Ribatti, D. et al. IL-6 Contributes to the TGF-β1-Mediated Epithelial to Mesenchymal Transition in Human Salivary Gland Epithelial Cells. Arch. Immunol. Ther. Exp. 68, 27 (2020). https://doi.org/10.1007/s00005-020-00591-5

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