Interferon-alpha regulates expression of lncRNA MALAT1 and interferon-stimulated genes, as well as chemokine production, in primary Sjögren's syndrome.

Abstract

This study aimed to explore the contribution of interferon-alpha (IFN-α) to MALAT1 expression in primary Sjögren's syndrome (pSS). Peripheral blood mononuclear cells (PBMC) from pSS patients and healthy blood donors were stimulated with recombinant human IFN-α, and the expression levels of MALAT1 and several interferon-stimulated genes (ISGs) were measured by RT-PCR, while supernatant levels of interferon-regulated chemokines were measured using multiplex cytokine immunobead assay. In this work, we found that MALAT1 expression levels were increased in IFN-α-stimulated PBMC from pSS patients and healthy controls. As expected, ISG expression levels and interferon-regulated chemokine secretion levels were higher after IFN-α stimulation. However, the fold-change values for ISG15, Ly6E, OAS1, and OASL expression levels were higher in cells from pSS patients than in controls. Similarly, PBMC from pSS patients produced higher concentrations of chemokines than those from healthy controls after IFN-α stimulation. Our data provide insights into the abnormal IFN-α-mediated regulation of the lncRNA MALAT1 in pSS. Based on an unusually high capacity of PBMC to express ISG and to produce interferon-responsive chemokines, it is likely that targeted therapies to block these molecules may be of benefit to patients with pSS.