LncRNA AFAP1-AS1 mediates therapy-dependent expression of CCL5, CXCL10 and MMP9 in multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by inflammation, areas of demyelination and axonal loss called plaques, recruitment of lymphocytes and monocytes, and bursts of focal blood-brain barrier leakage. Treatment strategies for MS focus on delaying disease progression and increasing patients’ quality of life. However, most therapies have inconsistent efficacies and are associated with various side effects. Recently, long non-coding RNAs have been found to play a major role in the pathogenesis and development of several diseases. Several long non-coding RNAs have been correlated with MS. We focus on the role of AFAP1-AS1 in regulating the function of M2 macrophages, one of the immune cells believed to attenuate MS. Assessing this long non-coding RNA will improve our understanding of the molecular mechanics of immune cells in MS. We observe the impact of AFAP1-AS1 silencing in M2 macrophages on essential effector and regulatory proteins like MMP9, CCL5 and CXCL10 in MS patients receiving different treatments (Fingolimod, Interferon beta-1a, Interferon beta-1b, Teriflunomide or Dimethyl fumarate). Our results reported an upstream regulatory effect of AFAP1-AS1 on MMP9, CCL5, and CXCL10 in differently treated patients. By measuring the levels of proteins upon silencing of AFAP1-AS1, it was confirmed that this lncRNA has varying effects on the expression of these proteins depending on the treatment the patient is undergoing. These data shed light on the potential role of manipulating the anti-inflammatory activity of M2 cells making it a possible therapeutic target for certain MS patients. • AFAP1-AS1 is upregulated in M2 macrophages of differently treated MS patients. • Silencing of AFAP1-AS1 alters MMP9, CCL5, and CXCL10 expression in M2 cells. • Protein expression to AFAP1-AS1 silencing varies according to the type of MS treatment. • Fingolimod and Interferon beta-1a groups showed MMP9 upregulation after silencing of AFAP1-AS1. • AFAP1-AS1 may serve as a therapy-specific regulatory target in MS.