Tofacitinib counteracts IL-6 overexpression induced by deficient autophagy: implications in Sjögren's syndrome.

Rheumatology
María-José BarreraMaría-Julieta González

Abstract

Altered homeostasis of salivary gland (SG) epithelial cells in Sjögren's syndrome (SS) could be the initiating factor that leads to inflammation, secretory dysfunction and autoimmunity. Autophagy is an important homeostatic mechanism, whose deficiency is associated with inflammation and accumulation of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) components. We aimed to evaluate whether autophagy is altered in labial SG (LSG) epithelial cells from primary SS (pSS) patients and whether this contributes to inflammation through the JAK-STAT pathway. Furthermore, we investigated the anti-inflammatory effect of the JAK inhibitor tofacitinib in autophagy-deficient (ATG5 knockdown) three-dimensional (3D)-acini. We analysed LSG biopsies from 12 pSS patients with low focus score and 10 controls. ATG5-deficient 3D-acini were generated and incubated with IL-6 in the presence or absence of tofacitinib. Autophagy markers, pro-inflammatory cytokine expression, and JAK-STAT pathway activation were evaluated by PCR or western blot, along with correlation analyses between the evaluated markers and clinical parameters. LSG from pSS patients showed increased p62 and decreased ATG5 expression, correlating negatively w...Continue Reading

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Citations

Apr 4, 2021·International Journal of Molecular Sciences·Toshimasa ShimizuAtsushi Kawakami
Jul 30, 2021·Expert Opinion on Pharmacotherapy·Soledad RetamozoPilar Brito-Zerón
Nov 4, 2021·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Bin WangGuixiu Shi

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