Bacterial endotoxin-lipopolysaccharide role in inflammatory diseases: An overview

Document Type : Review Article

Authors

1 Galgotias College of Pharmacy, Greater Noida, U.P., India

2 Banasthali Vidyapith, Department of Pharmacy, Rajasthan, India

3 Department of Pharmacology, All India Institute of Medical Sciences, Rishikesh 249203, India

Abstract

Despite advancements in antimicrobial and anti-inflammatory treatments, inflammation and its repercussions continue to pose a considerable challenge in medicine. Acute inflammation may cause life-threatening conditions like septic shock, while chronic inflammation leads to tissue degeneration and impaired function. Lipopolysaccharides (LPS), a well-known pathogenic trigger contributing to several dysfunctions, is a crucial part of the outer membrane of gr-negative bacteria. LPS are well-known for eliciting acute inflammatory responses by activating a pathogen-associated molecular pattern (PAMP), which stimulates the innate immune system and triggers local or systemic inflammatory responses. LPS also activate numerous intracellular molecules that modulate the expression of a wide range of inflammatory mediators. These mediators subsequently initiate or exacerbate various inflammatory processes. Beyond immune cells, LPS can also activate non-immune cells, leading to inflammatory reactions. These excessive inflammatory responses are often detrimental and typically result in chronic and progressive inflammatory diseases, including neurodegenerative, cardiovascular diseases, and cancer. This review delves into the mechanisms by which the bacterial endotoxin LPS contribute to multiple inflammatory diseases. These insights into LPS signaling pathways could inform the design of new treatment strategies such as TLR4, NLRP3, HMGA1, MAPK, and NF-kB inhibitors. This enables precise targeting of inflammation-related processes in disease management.

Keywords

Main Subjects

References

1. Page MJ, Kell DB, Pretorius E. The role of lipopolysaccharide-induced cell signalling in chronic inflammation. Chronic Stress 2022; 6: 1-18. 
2. Skrzypczak-Wiercioch A, Sałat K. Lipopolysaccharide-induced model of neuroinflammation: Mechanisms of action, research application and future directions for its use. Molecules 2022; 27: 5481-5490. 
3. Jiang D, Yang Y, Li D. Lipopolysaccharide induced vascular smooth muscle cells proliferation: A new potential therapeutic target for proliferative vascular diseases. Cell Prolif 2017; 50: 12332-12340.
4. Liu X, Yao JJ, Chen Z, Lei W, Duan R, Yao Z. Lipopolysaccharide sensitizes the therapeutic response of breast cancer to IAP antagonist. Front Immunol 2022; 13: 906357-906373.
5. Killeen SD, Wang JH, Andrews EJ, Redmond HP. Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-κB-dependent activation of the urokinase plasminogen activator system. Br J Cancer 2009; 100: 1589–1602 
6. Wang EL, Qian ZR, Nakasono M, Tanahashi T, Yoshimoto K, Bando Y, et al. High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer. Br J cancer 2010; 102: 908-915.
7. Raetz CR, Reynolds CM, Trent MS, Bishop RE. Lipid A modification systems in Gram-negative bacteria. Annu Rev Biochem 2007; 76: 295-329.
8. Raetz CRH, Whitfield C. Lipopolysaccharide endotoxins. Annu Rev Biochem 2002; 71: 635-700.
9. Mazgaeen L, Gurung P. Recent advances in lipopolysaccharide recognition systems. Int J Mol Sci 2020; 21: 379-397. 
10. Klein G, Lindner B, Brabetz W, Brade H, Raina S. Escherichia coli K-12 suppressor-free mutants lacking early glycosyltransferases and late acyltransferases: Minimal lipopolysaccharide structure and induction of envelope stress response. J Biol Chem 2009; 284: 15369-15389.
11. Page MJ, Kell DB, Pretorius E. The role of lipopolysaccharide-induced cell signaling in chronic inflammation. Chronic Stress (Thousand Oaks) 2022; 6: 1-18. 
12. Ebbensgaard A, Mordhorst H, Aarestrup FM, Hansen EB. The role of outer membrane proteins and lipopolysaccharides for the sensitivity of Escherichia coli to antimicrobial peptides. Front Microbiol 2018; 9: 2153-2166. 
13. Klein G, Raina S. Regulated assembly of LPS, its structural alterations, and cellular response to LPS defects. Int J Mol Sci 2019; 20: 356-378. 
14. Ashraf KU, Nygaard R, Vickery ON, Erramilli SK, Herrera CM, McConville TH, et al. Structural basis of lipopolysaccharide maturation by the O-antigen ligase. Nature 2022; 604: 371–376. 
15. Gorman A, Golovanov AP. Lipopolysaccharide structure and the phenomenon of low endotoxin recovery. Eur J Pharm Biopharm 2022; 180: 289-307. 
16. Furevi A, Ståhle J, Muheim C, Gkotzis S, Daley DO, Udekwu KI, et al. Elucidation of the O-antigen structure of Escherichia coli O93 and characterization of its biosynthetic genes. Glycobiology 2023; 33: 289-300. 
17. Wang J, Qin C, Xu Y, Yin J, Hu J, Guo X. Structural and genetic identification of the O-antigen from an Escherichia coli isolate, SD2019180, representing a novel serogroup. Int J Mol Sci 2023; 24: 15040-15055.
18. Liu B, Furevi A, Perepelov AV, Guo X, Cao H, Wang Q, et al. Structure and genetics of Escherichia coli O antigens. FEMS Microbiol Rev 2020; 44: 655-683. 
19. Fux AC, Casonato Melo C, Michelini S, Swartzwelter BJ, Neusch A, Italiani P, et al. Heterogeneity of lipopolysaccharide as a source of variability in bioassays and LPS-binding proteins as a remedy. Int J Mol Sci 2023; 24: 8395-8429. 
20. Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: Update from the GBD 2019 study. J Am Coll Cardiol 2020; 76: 2982-3021. 
21. Zhang Y, Feng Y, Zhou S, Gao S, Xiong B, Gao X, et al. Establishment of a model of LPS-induced inflammatory injury in human aortic endothelial cells. Biomed Pharmacother 2024; 174: 116576-116582.
22. Henein MY, Vancheri S, Longo G, Vancheri F. The role of inflammation in cardiovascular disease. Int J Mol Sci 2022; 23: 12906-12911. 
23. Krüger-Genge A, Blocki A, Franke RP, Jung F. Vascular endothelial cell biology: An update. Int J Mol Sci 2019; 20: 4411-4419. 
24. Kong P, Cui ZY, Huang XF, Zhang DD, Guo RJ, Han M. Inflammation and atherosclerosis: Signaling pathways and therapeutic intervention. Sig Transduct Target Ther 2022; 7: 131-140.
25. Medina-Leyte DJ, Zepeda-García O, Domínguez-Pérez M, González-Garrido A, Villarreal-Molina T, Jacobo-Albavera L. Endothelial dysfunction, inflammation and coronary artery disease: Potential biomarkers and promising therapeutical approaches. Int J Mol Sci 2021; 22: 3850- 3859.
26. Sun F, Xu K, Zhou J, Zhang W, Duan G, Lei M. Allicin protects against LPS-induced cardiomyocyte injury by activating Nrf2-HO-1 and inhibiting NLRP3 pathways. BMC Cardiovasc Disord 2023; 23: 410-419.
27. Walley KR. Sepsis-induced myocardial dysfunction. Curr Opin Crit Care 2018; 24: 292-299.  
28. Chen D, Jin Z, Zhang J, Jiang L, Chen K, He X, et al. HO-1 protects against Hypoxia/Reoxygenation-Induced mitochondrial dysfunction in H9c2 cardiomyocytes. PLoS ONE 2016; 11: e0153587-153604.
29. Jiang CS, Zhuang CL, Zhu K, Zhang J, Muehlmann LA, Figueiró Longo JP, et al. Identification of a novel small-molecule Keap1-Nrf2 PPI inhibitor with cytoprotective effects on LPS-induced cardiomyopathy. J Enzyme Inhib Med Chem 2018; 33: 833–841.
30. Sun HJ, Wu ZY, Nie XW, Bian JS. Role of endothelial dysfunction in cardiovascular diseases: The link between inflammation and hydrogen sulfide. Front Pharmacol 2020; 10: 1568-1572.
31. Cowan DB, Noria S, Stamm C, Garcia LM, Poutias DN, del Nido PJ, McGowan Jr FX. Lipopolysaccharide internalization activates endotoxin-dependent signal transduction in cardiomyocytes. Circ Res 2001; 88: 491-498. 
32. Natanson C, Danner RL, Elin RJ, Hosseini JM, Peart KW, Banks SM, et al. Role of endotoxemia in cardiovascular dysfunction and mortality. Escherichia coli and Staphylococcus aureus challenges in a canine model of human septic shock. The J Clin Invest 1989; 83: 243-251.
33. Ognibene FP, Parker MM, Natanson C, Shelhamer JH, Parrillo JE. Depressed left ventricular performance: Response to volume infusion in patients with sepsis and septic shock. Chest 1988; 93: 903-910.
34. Parker MM, Shelhamer JH, Bacharach SL, Green MV, Natanson C, Frederick TM, et al. Profound but reversible myocardial depression in patients with septic shock. Ann Intern Med 1984; 100: 483-490.
35. Yücel G, Zhao Z, El-Battrawy I, Lan H, Lang S, Li X, et al. Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell-derived cardiomyocytes. Sci Rep 2017; 7: 2935-2942.
36. Giannino G, Braia V, Griffith Brookles C, Giacobbe F, D’Ascenzo F, Angelini F, et al. The intrinsic cardiac nervous system: From pathophysiology to therapeutic implications. Biol 2024; 13: 105-111.
37. Yang D, Dai X, Xing Y, Tang X, Yang G, Harrison AG, et al. Intrinsic cardiac adrenergic cells contribute to LPS-induced myocardial dysfunction. Commun Biol 2022 5: 96-111. 
38. Yang D, Dai X, Xing Y, Tang X, Yang G, Wang P. Intrinsic cardiac adrenergic cells contribute to septic cardiomyopathy. bioRxiv 2021; 2: 2021-2033. 
39. Wang HY, Liu XY, Han G, Wang ZY, Li XX, Jiang ZM, et al. LPS induces cardiomyocyte injury through calcium-sensing receptor. Mol Cell Biochem 2013; 379: 153-159. 
40. Moriya J. Critical roles of inflammation in atherosclerosis. J Cardiol 2019; 73: 22-27. 
41. Wolf D, Ley K. Immunity and inflammation in atherosclerosis. Cir Res 2019; 124: 315-327.
42. Triantafilou M, Gamper FG, Lepper PM, Mouratis MA, Schumann C, Harokopakis E, et al. Lipopolysaccharides from atherosclerosis‐associated bacteria antagonize TLR4, induce formation of TLR2/1/CD36 complexes in lipid rafts and trigger TLR2‐induced inflammatory responses in human vascular endothelial cells. Cell Microbiol 2007; 9: 2030-2039.
43. Sieve I, Ricke-Hoch M, Kasten M, Battmer K, Stapel B, Falk CS et al. A positive feedback loop between IL-1β, LPS and NEU1 may promote atherosclerosis by enhancing a proinflammatory state in monocytes and macrophages. Vascul Pharmacol 2018; 103: 16-28.
44. Wang J, Si Y, Wu C, Sun L, Ma Y, Ge A, et al. Lipopolysaccharide promotes lipid accumulation in human adventitial fibroblasts via TLR4-NF-κB pathway. Lipids Health Dis 2012; 11: 139 -142.
45. Griendling KK, Sorescu D, Ushio-Fukai M. NAD (P) H oxidase: role in cardiovascular biology and disease. Circ Res 2000; 86: 494-501.
46. Loffredo L, Ivanov V, Ciobanu N, Deseatnicova E, Gutu E, Mudrea L, et al. Is there an association between atherosclerotic burden, oxidative stress, and gut-derived lipopolysaccharides? Antioxid Redox Signal 2020; 6: 761-766.
47. DeLeo FR, Renee J, McCormick S, Nakamura M, Apicella M, Weiss JP, et al. Neutrophils exposed to bacterial lipopolysaccharide upregulate NADPH oxidase assembly. J Clin Invest 1998;101: 455-463.
48. De KWG, Alexander RW, Ushio-Fukai M, Ishizaka N, Griendling KK. Tumour necrosis factor α activates a p22phox-based NADH oxidase in vascular smooth muscle. Biochem J 1998; 329: 6537-6542.
49. Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 1994; 74: 11418-11423.
50. Belmadani S, Matrougui K. Role of high mobility group box 1 in cardiovascular diseases. Inflammation 2022; 45: 1864-1874. 
51. Xie Q, Yao Q, Hu T, Cai Z, Zhao J, Yuan Y, et al. High-mobility group A1 promotes cardiac fibrosis by upregulating FOXO1 in fibroblasts. Front Cell Dev Biol 2021; 9: 666422-666433. 
52. Cai ZL, Shen B, Yuan Y, Liu C, Xie QW, Hu TT, et al. The effect of HMGA1 in LPS-induced myocardial inflammation. Int J Biol Sci 2020; 16: 1798-1810. 
53. Hu K, Jiang P, Hu J, Song B, Hou Y, Zhao J, et al. Dapagliflozin attenuates LPS-induced myocardial injury by reducing ferroptosis. J Bioenerg Biomembr 2024; 5: 361-371.
54. Marshall JS, Warrington R, Watson W, Kim HL. An introduction to immunology and immunopathology. Allergy Asthma Clin Immunol 2018; 14: 1-8. 
55. Li D, Wu M. Pattern recognition receptors in health and diseases. Sig Transduct Target Ther 2021; 6: 291-315.
56. Papadakos SP, Arvanitakis K, Stergiou IE, Lekakis V, Davakis S, Christodoulou MI, et al. The role of TLR4 in the immunotherapy of hepatocellular carcinoma: Can we teach an old dog new tricks? Cancers 2023; 15: 2795-2825. 
57. Armstrong H, Bording-Jorgensen M, Dijk S, Wine E. The complex interplay between chronic inflammation, the microbiome, and cancer: understanding disease progression and what we can do to prevent it. Cancers 2018; 10: 83-102. 
58. Ketcham CM, Anai S, Reutzel R, Sheng S, Schuster SM, Brenes RB, et al. p37 induces tumor invasiveness. Mol Cancer Ther 2005; 4: 1031–1038. 
59. Tanih NF, Okeleye BI, Ndip LM, Clarke AM, Naidoo N, Mkwetshana N, et al. Helicobacter pylori prevalence in dyspeptic patients in the Eastern Cape province - race and disease status. S Afr Med J 2010; 100:734–737. 
60. Hamada T, Zhang X, Mima K, Bullman S, Sukawa Y, Nowak JA, et al. Fusobacterium nucleatum in colorectal cancer relates to immune response differentially by tumor microsatellite instability status. Cancer Immunol Res 2018; 6: 1327-1336.
61. Chen T, Li Q, Zhang X, Long R, Wu Y, Wu J, et al. TOX expression decreases with the progression of colorectal cancers and is associated with CD4 T-cell density and Fusobacterium nucleatum infection. Hum Pathol 2018; 79: 93-101.
62. Parhi L, Alon-Maimon T, Sol A, Nejman D, Shhadeh A, Levi TF, et al. Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression. Nat Commun 2020; 11: 3259-3271. 
63. Liu X, Yao JJ, Chen Z, Lei W, Duan R, Yao Z. Lipopolysaccharide sensitizes the therapeutic response of breast cancer to IAP antagonist. Front Immunol 2022;13: 906357-906373. 
64.    Li J, Yang F, Wei F, Ren X. The role of toll-like receptor 4 in tumor microenvironment. Oncotarget 2017; 8: 66656-66667. 
65. Liu WT, Jing YY, Yan F, Han ZP, Lai FB, Zeng JX, et al. LPS-induced CXCR4-dependent migratory properties and a mesenchymal-like phenotype of colorectal cancer cells. Cell Adh Migr 2017; 11: 13–23.
66. Li XY, Yang X, Zhao QD, Han ZP, Liang L, Pan XR, et al. Lipopolysaccharide promotes tumorigenicity of hepatic progenitor cells by promoting proliferation and blocking normal differentiation. Cancer Lett 2017; 386: 35–46. 
67. Chen C, Khismatullin DB. Lipopolysaccharide induces the interactions of breast cancer and endothelial cells via activated monocytes. Cancer Lett 2014; 345: 75–84. 
68. Ying J, Zhou HY, Liu P, You Q, Kuang F, Shen YN, et al. Aspirin inhibited the metastasis of colon cancer cells by inhibiting the expression of toll-like receptor 4. Cell Biosci 2018; 8: 1-15.
69. Zhu G, Huang Q, Huang Y, Zheng W, Hua J, Yang S, et al. Lipopolysaccharide increases the release of VEGF-C that enhances cell motility and promotes lymphangiogenesis and lymphatic metastasis through the TLR4-NF-κB/JNK pathways in colorectal cancer. Oncotarget 2016; 7: 73711–73724. 
70. Wu W. PD-L1 induced by lipopolysaccharide via TLR4/MyD88/NF-κB pathway promotes immune escape in pancreatic cancer. HPB 2021; 23: S234. 
71. Massoumi RL, Teper Y, Ako S, Ye L, Wang E, Hines OJ, et al. Direct effects of lipopolysaccharide on human pancreatic cancer cells. Pancreas 2021; 50: 524–528. 
72. Yin H, Pu N, Chen Q, Zhang J, Zhao G, Xu X, et al. Gut-derived lipopolysaccharide remodels tumoral microenvironment and synergizes with PD-L1 checkpoint blockade via TLR4/MyD88/AKT/NF-κB pathway in pancreatic cancer. Cell Death Dis 2021; 12: 1033-1047. 
73. Wilkie T, Verma AK, Zhao H, Charan M, Ahirwar DK, Kant S, et al. Lipopolysaccharide from the commensal microbiota of the breast enhances cancer growth: Role of S100A7 and TLR4. Mol Oncol 2022; 16: 1508–1522. 
74. Li S, Xu X, Jiang M, Bi Y, Xu J, Han M. Lipopolysaccharide induces inflammation and facilitates lung metastasis in a breast cancer model via the prostaglandin E2-EP2 pathway. Mol Med Rep 2015; 11: 4454-4462. 
75. Chen C, Khismatullin DB. Lipopolysaccharide induces the interactions of breast cancer and endothelial cells via activated monocytes. Cancer Lett 2014; 345: 75-84. 
76. Muhammad JS, Nanjo S, Ando T, Yamashita S, Maekita T, Ushijima T, et al. Autophagy impairment by Helicobacter pylori-induced methylation silencing of MAP1LC3Av1 promotes gastric carcinogenesis. Int J Cancer 2017; 140: 2272–2283.
77. Zhou Y, Xia L, Liu Q, Wang H, Lin J, Oyang L, et al. Induction of proinflammatory response via activated macrophage-mediated NF-κB and STAT3 pathways in gastric cancer cells. Cell Physiol Biochem 2018; 47: 1399–1410.
78. Xiao Z, Su Z, Han S, Huang J, Lin L, Shuai X. Dual pH-sensitive nanodrug blocks PD-1 immune checkpoint and uses T cells to deliver NF-κB inhibitor for antitumor immunotherapy. Sci Adv 2020; 6: 7785-7797.
79. Nakazawa N, Yokobori T, Sohda M, Hosoi N, Watanabe T, Shimoda Y, et al. Significance of lipopolysaccharides in gastric cancer and their potential as a biomarker for nivolumab sensitivity. Int J Mol Sci 2023; 24: 11790-11800. 
80. Liu WT, Jing YY, Gao L, Li R, Yang X, Pan XR, et al. Lipopolysaccharide induces the differentiation of hepatic progenitor cells into myofibroblasts constitutes the hepatocarcinogenesis-associated microenvironment. Cell Death Differ 2020; 27: 85-101. 
81. Wang L, Zhu R, Huang Z, Li H, Zhu H. Lipopolysaccharide-induced Toll-like receptor 4 signaling in cancer cells promotes cell survival and proliferation in hepatocellular carcinoma. Dig Dis Sci 2013; 58: 2223–2236. 
82. Patil VS, Harish DR, Sampat GH, Roy S, Jalalpure SS, Khanal P, et al. System biology investigation revealed lipopolysaccharide and alcohol-induced hepatocellular carcinoma resembled hepatitis B virus immunobiology and pathogenesis. Int J Mol Sci 2023; 24: 11146-11169.  
83. Muzio L, Viotti A, Martino G. Microglia in neuroinflammation and neurodegeneration: From understanding to therapy. Front Neurosci 2021: 15: 742065-742072.
84. Lehnardt S, Lachance C, Patrizi S, Lefebvre S, Follett PL, Jensen FE, et al. The toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS. J Neurosci 2002; 22: 2478-2486.
85. Mrak RE, Griffin WS. Glia and their cytokines in progression of neurodegeneration. Neurobiol Aging 2005; 26: 349-354.
86. Liu BI, Hong JS. Role of microglia in inflammation-mediated neurodegenerative diseases: Mmechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther 2003; 304: 1-7.
87. Cookson MR. Alpha-Synuclein and neuronal cell death. Mol Neurodegener 2009; 4: 9-23.
88. Dauer W, Przedborski S. Parkinson’s disease: Mechanisms and models. Neuron 2003; 39: 889-909.
89. Javoy-Agid F, Agid Y. Is the mesocortical dopaminergic system involved in Parkinson disease? Neurology 1980; 30: 1326-.1332.
90. Hunter R, Ojha U, Bhurtel S, Bing G, Choi DY. Lipopolysaccharide-induced functional and structural injury of the mitochondria in the nigrostriatal pathway. Neurosci Res 2017; 114: 62-69.
91. Castano A, Herrera AJ, Cano J, Machado A. The degenerative effect of a single intranigral injection of LPS on the dopaminergic system is prevented by dexamethasone, and not mimicked by rh‐TNF‐α, IL‐1β and IFN‐γ. J Neurochem 2002; 81: 150-157.
92. Park JS, Davis RL, Sue CM. Mitochondrial dysfunction in Parkinson’s disease: New mechanistic insights and therapeutic perspectives. Curr Neurol Neurosci Rep 2018; 18: 1-12.
93. Ruano D, Revilla E, Gavilán MP, Vizuete ML, Pintado C, et al. Role of p38 and inducible nitric oxide synthase in the in vivo dopaminergic cells’ degeneration induced by inflammatory processes after lipopolysaccharide injection. Neuroscience 2006; 140: 1157-1168.
94. Ittner LM, Götz J. Amyloid-β and tau—a toxic pas de deux in Alzheimer’s disease. Nat Rev Neurosci 2011; 12: 67-72.
95. Hauss-Wegrzyniak B, Dobrzanski P, Stoehr JD, Wenk GL. Chronic neuroinflammation in rats reproduces components of the neurobiology of Alzheimer’s disease. Brain Res 1998; 780: 294-303.
96. Sheng JG, Bora SH, Xu G, Borchelt DR, Price DL, Koliatsos VE. Lipopolysaccharide-induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid β peptide in APPswe transgenic mice. Neurobiol Dis 2003; 14: 133-145.
97. Lee JW, Lee YK, Yuk DY, Choi DY, Ban SB, Oh KW, et al. Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. J Neuroinflamm 2008; 5: 37-51.
98. Hsiao HY, Chen YC, Chen HM, Tu PH, Chern Y. A critical role of astrocyte-mediated nuclear factor-κB-dependent inflammation in Huntington’s disease. Hum Mol Genet 2013; 22: 1826-1842.
99. Turner RC, Naser ZJ, Lucke-Wold BP, Logsdon AF, Vangilder RL, Matsumoto RR, et al. Single low-dose lipopolysaccharide preconditioning: neuroprotective against axonal injury and modulates glial cells. Neuroimmunol Neuroinflamm 2017; 4: 6-18.
100. Kanekiyo T, Bu G. The low-density lipoprotein receptor-related protein 1 and amyloid-β clearance in Alzheimer’s disease. Front Aging Neurosci 2014; 6: 93-99.
101. Jaeger LB, Dohgu S, Sultana R, Lynch JL, Owen JB, Erickson MA, et al. Lipopolysaccharide alters the blood-brain barrier transport of amyloid β protein: A mechanism for inflammation in the progression of Alzheimer’s disease. Brain Behav Immun 2009; 23: 507-517.
102. Barton SM, Janve VA, McClure R, Anderson A, Matsubara JA, Gore JC, et al. Lipopolysaccharide induced opening of the blood brain barrier on aging 5XFAD mouse model. J Alzheimers Dis 2019; 67: 503-513.
103. Wang LM, Wu Q, Kirk RA, Horn KP, Salem AH, Hoffman JM, et al. Lipopolysaccharide endotoxemia induces amyloid-β and p-tau formation in the rat. Brain Am J Nucl Med Mol Imaging 2018; 8: 86-92.
104. Ma L, Zhang H, Liu N, Wang PQ, Guo WZ, Fu Q, et al. TSPO ligand PK11195 alleviates neuroinflammation and beta-amyloid generation induced by systemic LPS administration. Brain Res Bull 2016; 121: 192–200.
105. Lykhmus O, Mishra N, Koval L, Kalashnyk O, Gergalova G, Uspenska K, et al. Molecular mechanisms regulating LPS-induced inflammation in the brain. Front Mol Neurosci 2016; 9: 19-26.
Iranian Journal of Basic Medical Sciences
Volume 28, Issue 5
May 2025
Pages 553-564

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