Effects of GPNMB in the modulation of neuroinflammation induced by LPS in microglia and astrocytes.

Author(s)

Marina Saade

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2021-08-13

Examining board members

Cristoforo Scavone; Carolina Demarchi Munhoz; Luis Eduardo Menezes Quintas; Andréa da Silva Torrão

• Advisor: Cristoforo Scavone

Abstract

GPNMB is an endogenous transmembrane glycoprotein that can be cleaved by ADAM10, and its extracellular fragment can interact with a transmembrane protein called Na+/K+-ATPase (NKA). NKA, which is known for its essential role in electrolytic control and cell survival, also has a signaling role in several pathways that influence inflammatory processes. Acute inflammation is a cellular defense process. However, when inflammation is not controlled, several other cellular processes are triggered, which can be harmful to the organism. Most studies indicate that GPNMB has an anti-inflammatory role, both in the periphery and in the central nervous system (CNS). In the CNS inflammatory processes are mainly mediated by glial cells, predominantly by microglia. Thus, this project aimed to evaluate the role of GPNMB in neuroinflammation triggered by lipopolysaccharide (LPS) in primary cultures of glial cells and in a microglia cell line. This study contributes to elucidate the effects of GPNMB as a possible new therapeutic target for neurodegenerative diseases, since neuroinflammation is a pattern found in these diseases. Since GPNMB did not modulate cell viability, the concentration of 25ng/mL of GPNMB was chosen for primary culture cells, and 2.5<font face = \"symbol\">mg/mL for line cells, while the chosen LPS concentration was 1<font face = \"symbol\">mg/mL for all cell types. Treatment of GPNMB for 30 minutes was unable to activate the ERK and Akt pathways. The administration of GPNMB with LPS for 30 minutes does not seem to affect the mRNA levels of the cytokines TNF-<font face = \"symbol\">a and IL-10, but it does affect the transcription of IL-1<font face = \"symbol\">b. However, the pretreatment of GPNMB followed by a LPS challenge does not modulate the transcription of any of the cytokines studied in the chosen concentrations. These data corroborate previous studies that point to an anti-inflammatory role for GPNMB, suggesting that this role also extends to primary cultured cells. (AU)

• FAPESP's process: 18/07896-3 - Effects of GPNMB pretein in the modulation of inflammatory processes induced by LPS in microglial cells and astrocytes rat cells
• Grantee: Marina Saade
• Support Opportunities: Scholarships in Brazil - Master