1.Inhibition of GSK-3 by Tideglusib Suppresses Activated Macrophages and Inflammatory Responses in Lipopolysaccharide-stimulated RAW 264.7 Cell Line
Nur Fatin Zalikha Zailan ; Niranjana Jaganathan ; Thiban Sandramuti ; Seri Narti Edayu Sarchio ; Masriana Hassan
Malaysian Journal of Medicine and Health Sciences 2020;16(Supp 9, November):2-8
Introduction: Glycogen synthase kinase-3 (GSK-3) is an important immune regulator that controls inflammation via inhibition of its protein kinase activities. Persistent inflammatory responses through the activation of
immune cells and excessive production of immune mediators may cause tissue destruction and implicated in the development of chronic inflammatory diseases. The objective of this study was to examine the role of Tideglusib,
a GSK-3 inhibitor, in inflammatory responses elicited through macrophage activation by investigating the
expression of cell surface biomarkers and inflammatory molecule levels. Method: The effects of GSK-3 inhibition by Tideglusib on the expression of CD11b and CD40 and secretion of pro-inflammatory cytokines in the
lipopolysaccharide (LPS)-activated macrophage-derived RAW 264.7 cells were determined by flow cytometry, while the presence of nitric oxide (NO) was determined by Griess assay. Results: Stimulation of RAW 264.7 cells with LPS increased substantial levels of CD11b and CD40 expressions, and secretion of NO, TNF-α, and MCP-1. However, the expression of these molecules was suppressed through inhibition of GSK-3. Conclusion: These findings suggest the significant role of Tideglusib to limit the upregulation of immune responses in activated macrophages, and as a potential anti-inflammatory drug for the intervention and treatment of inflammatory diseases.
2.Assessment of Pathogenicity of Community-Acquired MRSA Isolates in Mice-Induced Peritonitis
Nur Izzatie Zulkiflee ; Norhidayah Mat Azis ; Mohd Nasir Mohd Desa ; Norhafizah Mohtarrudin ; Sharifah Sakinah Syed Alwi ; Seri Narti Edayu Sarchio
Malaysian Journal of Medicine and Health Sciences 2021;17(No.3):8-15
Introduction: Methicillin-Resistance Staphylococcus aureus (MRSA) is known as a major nosocomial pathogen in
healthcare. However, it has now spread in the community known as community-acquired MRSA (CA-MRSA). Thus,
the survival and pathogenicity of CA-MRSA isolates were assessed using in vivo peritonitis model with comparison to
ATCC-MRSA. Two CA-MRSA isolates; CA-MRSA1 and CA-MRSA2 that were isolated from healthy population, were
studied and compared. Methods: Mice were assigned into 4 groups and injected intraperitoneally with ATCC-MRSA,
CA-MRSA1 or CA-MRSA2, respectively. Sterile Dulbecco’s Phosphate-Buffered Saline (DPBS) represents negative
control. Mice were observed twice daily, 0-72 hours of post-infection. Any signs of distress were recorded for severity score and survival analyses. Mice were euthanised at 72 hours post-inoculation or by referring to the Peritonitis
Severity Scoring (PSS) system. Organs of interest, peritoneal lavage and abscess were processed for bacterial counts.
Tissue samples were analysed for histopathological scores. Results: All mice inoculated with MRSA showed clear
signs of illness with peritonitis symptoms of p<0.001 and comparable PSS scores were recorded in all infected mice
groups. Intraperitoneal injection of lethal dose of MRSA resulted in significant death of ATCC-MRSA (p<0.05) and
CA-MRSA-infected mice (p<0.01), compared to the un-infected. Bacterial burden was significantly high in all samples harvested from mice challenged with CA-MRSA2 compared to ATCC-MRSA except in abscess and lung. Significant liver necrosis and spleen inflammation were observed in CA-MRSA1, and lung inflammation in ATCC-MRSA-infected mice. Conclusion: Nasal carriage CA-MRSA isolates from a healthy population has the potential to cause
peritonitis with comparable severity as ATCC-MRSA.