Interferon-beta induces major histocompatibility complex of class I (MHC-I) expression and a proinflammatory phenotype in cultivated human astrocytes

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Ignarro, Raffaela Silvestre ; Bombeiro, Andre Luis ; Chiarotto, Gabriela Bortolanca ; Cartarozzi, Luciana Politti ; Coser, Lilian de Oliveira ; Ghizoni, Enrico ; Tedeschi, Helder ; Cendes, Fernando ; Lopes-Cendes, Iscia ; Rogerio, Fabio ; Rodrigues de Oliveira, Alexandre Leite

• Document type: Journal article
• Source: DIFFERENTIATION; v. 128, p. 14-pg., 2022-10-25.

Abstract

Major histocompatibility complex class I (MHC-I) has been implicated in several types of neuroplasticity phe-nomena. Interferon beta-1b (IFN-8) increases MHC-I expression by motoneurons after sciatic nerve crush in mice, improving axonal growth and functional recovery. Additionally, IFN-8 induces glial hypertrophy associated with upregulation of glial fibrillary acidic protein (GFAP) and MHC-I in murine astrocytes in vitro. As knowledge about MHC-I and its role in synaptic plasticity in human astrocytes (HAs) is scarce, we investigated these aspects in mature HAs obtained from the neocortex of patients undergoing surgery due to hippocampal sclerosis. Cells were exposed to media in the absence (0 IU/ml) or presence of IFN-8 for 5 days (500 IU/ml). Beta-2 microglobulin (82m), a component of the MHC-I, GFAP and vimentin proteins, was quantified by flow cytometry (FC) and increased by 100%, 60% and 46%, respectively, after IFN-8 exposure. We also performed qRT-PCR gene expression analyses for 82m, GFAP, vimentin, and pro-and anti-inflammatory cytokines. Our data showed that IFN-8-treated astrocytes displayed 82m and GFAP gene upregulation. Additionally, they presented a proin-flammatory profile with increase in the IL-6 and IL-18 genes and a tendency to upregulate TNF-a. Moreover, we evaluated the effect of HAs conditioned medium (CM) on the formation/maintenance of neurites/synapses by the PC12 lineage. Synaptophysin protein expression was quantified by FC. The CM of IFN-8-activated astrocytes was not harmful to PC12 neurites, and there was no change in synaptophysin protein expression. Therefore, IFN-8 activated HAs by increasing GFAP, vimentin and MHC-I protein expression. Like MHC-I modulation and astro-cyte activation may be protective after peripheral nerve damage and in some neurodegenerative conditions, this study opens perspectives on the pathophysiological roles of astroglial MHC-I in the human CNS. (AU)

• FAPESP's process: 17/03619-2 - Expression of Major Histocompatibility Complex Class I (MHC-I/HLA) and its receptor LilrB2 in brain tissue and primary cultures of human astrocytes
• Grantee: Raffaela Silvestre Ignarro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/05006-0 - Sensorimotor recovery following spinal root axotomy: use of different experimental approaches
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology
• Grantee: Fernando Cendes
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC