Synergistic effect of scavenger receptor A and low-density lipoprotein receptor on foam cell formation
Keywords:
Scavenger receptor A, Low-density lipoprotein receptor, RAW264.7 macrophages, Atherosclerosis, Inflammation
Abstract
The aim of the study is to investigate the effect of LPS on the expression of scavenger receptor A (SR-A) and low-density lipoprotein receptor (LDL-R) genes and proteins in RAW264.7 cell line. RAW264.7 cells were incubated in serum-free medium randomly in the absence or presence of low-density lipoprotein (LDL) alone, LDL+LPS and LPS alone. Intracellular cholesterol contents were assessed by Oil Red O staining cholesterol enzymatic assay, tumor necrosis factor α levels in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA), mRNA and protein ex-pressions of SR-A and LDL-R in the treated cells were assessed by semi-quantitative polymerase chain reaction and western blot, respectively. LPS was able to up regulate SR-A mRNA and protein expressions, override LDL-R suppression induced by a high dose of LDL and increase LDL uptake by enhancing receptor expression, leading to foam cell formation in Raw264.7 cells. Synergistic effect of the upregulation of SR-A and dysregulation of LDL-R under inflammatory stress may contribute to macrophage-derived foam cell formation.ÂReferences
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2. Wu C, Chen R, Liu M, Liu D, Li X, et al. Spiromastixones inhibit foam cell formation via regulation of cholesterol efflux and uptake in RAW264.7 macrophages. Mar Drugs 2015; 13(10): 6352–6365. doi: 10.3390/md13106352.
3. Gu HM, Zhang DW. Hypercholesterolemia, low density lipoprotein receptor and pro-protein convertase subtilisin/kexin-type 9. J Biomed Res 2015; 29(5): 356–361. doi: 10.7555/JBR.29.20150067.
4. Hu YW, Zhao JY, Li SF, Wang Q, Zheng L. Genome-wide profiling to analyze the effects of Ox-LDL induced THP-1 macrophage-derived foam cells on gene expression. Genom Data 2014; 2: 328–331. doi: 10.1016/j.gdata.2014.09.011.
5. Chistiakov DA, Bobryshev YV, Orekhov AN. Macrophage-mediated cholesterol handing in atherosclerosis. J Cell Mol Med 2015; 20(1): 17–28. doi: 10.1111/jcmm.12689.
6. Oberoi R, Bogalle EP, Matthes LA, Schuett H, Koch AK, et al. Lipocalin (LCN) 2 mediates pro-atherosclerotic processes and is elevated in patients with coronary artery disease. PLOS One 2015; 10(9): e0137924. doi: 10.1371/journal.pone.0137924.
7. Sherer Y, Zinger H, Shoenfeld Y. Atherosclerosis in systemic lupus erythematosus. Autoimmunity 2010; 43(1): 98–102. doi: 10.3109/08916930903374527.
8. Stojan G, Petri M. Atherosclerosis in systemic lupus erythematosus. J Cardiovasc Pharmacol 2013; 62(3): 255–262. doi: 10.1097/FJC.0b013e31829dd857.
9. Zani IA, Stephen SL, Mughal NA, Russell D, Homer-Vanniasinkam S, et al. Scavenger receptor structure and function in health and disease. Cells 2015; 4(2): 178–201. doi: 10.3390/cells4020178.
10. Ochiai A, Miyata S, Shimizu M, Inoue J, Sato R. Piperine induces hepatic low-density lipo-protein receptor expression through proteolytic activation of sterol regulatory element-binding proteins. PLOS One 2015; 10(10): e0139799. doi:10.1371/journal.pone.0139799.
11. Zhang Q, Ma ZSA, Wang C, Tang WQ, Song ZY. Nifedipine inhibits ox-LDL-induced lipid accumulation in human blood-derived macrophages. Biochem Biophys Res Commun 2015; 457(3): 440–444. doi: 10.1016/j.bbrc.2015.01.010.
12. Cai Y, Sukhova GK, Wong HK, Xu A, Tergaonkar V, et al. Rap1 induces cytokine production in pro-inflammatory macrophages through NFκB signaling and is highly expressed in human atherosclerotic lesions. Cell Cycle 2015; 14(22): 3580–3592. doi: 10.1080/15384101.2015.1100771.
13. Boshuizen MC, Hoeksema MA, Neele AE , van der Velden S, Hamers AA, et al. Interferon-β promotes macrophage foam cell formation by altering both cholesterol influx and efflux mechanisms. Cytokine 2015; 77: 220–226. doi: 10.1016/j.cyto.2015.09.016.
14. Rojas J, Salazar J, MartÃnez MS, Palmar J, Bautista J, et al. Macrophage heterogeneity and plasticity: Impact of macrophage biomarkers on atherosclerosis. Scientifica (Cairo) 2015; 2015: 851252. doi: 10.1155/2015/851252.
15. Zhou F, Pan Y, Huang Z, Jia Y, Zhao X, et al. Visfatin induces cholesterol accumulation in macrophages through up-regulation of scavenger receptor-A and CD36. Cell Stress Chaperones 2013; 18(5): 643–652. doi: 10.1007/s12192–013–0417–z.
16. Lee HY, Kim SD, Baek SH, Choi JH, Cho KH, et al. Serum amyloid A stimulates macrophage foam cell formation via lectin-like oxidized low-density lipoprotein receptor 1 upregulation. Biochem Biophys Res Commun 2013; 433(1): 18–23. doi: 10.1016/j.bbrc.2013.02.077.
17. Kelley JL, Ozment TR, Li C, Schweitzer JB, Williams DL. Scavenger receptor-A (CD204): A two-edged sword in health and disease. Crit Rev Immunol 2014; 34(3): 241–261. doi: 10.1615/CritRevImmunol.2014010267.
18. Yap NVL, Whelan FJ, Bowdish DME, Golding GB. The evolution of the scavenger receptor cysteine-rich domain of the class A scavenger receptors. Front Immunol 2015; 6: 342. doi: 10.3389/fimmu.2015.00342.
19. Van Berkel TJ, Van Velzen A, Kruijt JK, Suzuki H, Kodama T. Uptake and catabolism of modified LDL in scavenger-receptor class A type I/II knock-out mice. Biochem J 1998; 331(1): 29–35. doi: 10.1042/bj3310029.
20. Bist A, Fielding PE, Fielding CJ. Two sterol regulatory element-like sequences mediate up-regulation of caveolin gene transcription in response to low density lipoprotein free cholesterol. Proc Natl Acad Sci USA 1997; 94(20): 10693–10698. doi: 10.1073/pnas.94.20.10693.
21. Sato R. Sterol metabolism and SREBP activation. Arch Biochem Biophys 2010; 501(2): 177–181. doi: 10.1016/j.abb.2010.06.004.
Published
2017-01-19
Issue
Section
Original Research Article
Copyright (c) 2016 Zeng Guili, Chen Hao, Su Tianyi, Gong Jianping, Li Tao
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