Akademik Veri Yönetim Sistemi
JOURNAL OF BASIC AND CLINICAL HEALTH SCIENCES, cilt.5, sa.1, ss.6-13, 2021 (ESCI)
Objectives: Microglial cells are the central regulators of inflammatory responses in the brain and spinal cord. In addition to surveillance during resting state, they become activated due to microbial molecules and pathological insults. Endogenously expressed Activated protein C (APC) is an anticoagulant molecule with anti-inflammatory and cytoprotective roles, mediated by one of its receptors, Endothelial protein C receptor (EPCR). This study aimed to examine the basal and inducible expression of EPCR and unravel the regulatory mediators of its expression in microglia. Methods: We studied probable effects of Lipopolysaccharide (LPS), Peptidoglycan (PGN), and Polyinosinic-polycytidylic acid [Poly(I:C)] on EPCR mRNA and protein levels in N9 mouse microglial cells by qPCR and flow cytometry. Then, Cyclosporin A (CsA) and Mithramycin A (MMA) were used to inhibit the transcription factors; i) Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1), and ii) specificity protein 1 (Sp1) in the promoter region of the EPCR gene. Results: As a result, LPS and PGN stimulations led to the upregulation of EPCR expression in microglial cells. Inhibition of Sp1 and NFATc1 transcription factors in N9 cells showed that Sp1 transcription factor regulates LPS and PGN induced EPCR expression in N9 microglial cells. Also, for the PGN induced cells, NFATc1 seems to be regulating the expression of EPCR. Conclusion: Thus, our data suggest that LPS and PGN gave rise to increased EPCR levels in microglia, mainly through the Sp1 transcription factor.