The role of peroxisome proliferator activated receptor γ (PPARγ) ligands on foam cells formation derived from murine norovirus-1 (MNV-1) infected macrophage

The role of peroxisome proliferator activated receptor γ (PPARγ) ligands on foam cells formation derived from murine norovirus-1 (MNV-1) infected macrophage. Malaysian Journal of Medicine and Health Sciences, 15 (SUPP9): 4. pp. 20-29. ISSN 2636-9346 (2019)



Abstract

Introduction: Atherosclerosis is a chronic inflammatory disease initiated by the accumulation of macrophage derived foam cells in the intima layer of artery. In mice model of atherosclerosis, murine norovirus-4 has been shown to accelerate atherogenesis. In cells, lipid biometabolism is regulated by peroxisome proliferator activated receptor γ (PPARγ). Since PPARγ is predominantly expressed in macrophages and mice macrophages are MNV-1 proliferation-permissive host, we hypothesised that PPARγ ligands may regulate atherogenesis. Methods: MNV-1 was generated via RNA-based recovery system and used to infect the RAW 264.7 cells, then subjected to oxidized
low-density lipoprotein (oxLDL)-loaded and treated with ciglitazone or 15-deoxy-Delta(12,14)-PGJ(2)(15d-PGJ2). Foam cell formation was evaluated and the MNV-1 infection in all treatments was confirmed using virus titration (50% tissue culture infective dose; TCID50) and polymerase chain reaction (PCR). Results: Increment of lipid droplets was observed in all oxLDL treatment involving MNV-1 infection, ciglitazone or 15d-PGJ2 in the cytosol of RAW 264.7 cells over time compared to non-oxLDL treated cells. From the cholesterol ester (CE) content analysis amongst the oxLDL-loaded cells however, we found MNV-1 did not elicit increment of CE content. Treatment with 15d-PGJ2 resulted in increase of the CE content in oxLDL-treated cells. Interestingly, MNV-1 and ciglitazone had synergistic effect in reducing the CE content in oxLDL-treated cells. Conclusion: oxLDL stimulates foam cells formation in RAW 264.7 cells. However, MNV-1 infection did not contribute to RAW 264.7 cells derived-foam cells formation. On the other hand, 15d-PGJ2 promotes foam cells formation whilst ciglitazone inhibits the formation of foam cells derived from MNV-1-infected macrophages.

Item Type: Article
Keywords: Atherosclerosis, Ciglitazone, Foam cells, Murine norovirus-1 (MNV-1), 15d-PGJ2
Taxonomy: By Subject > Medicine > Biochemistry, Cell Biology and Genetics
By Subject > Medicine > Nervous System
Local Content Hub: Subjects > Medicine
Depositing User: Adi Azri Mohamad (Sg. Buloh)
Date Deposited: 07 Mar 2022 23:43
Last Modified: 09 Mar 2022 06:56
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