Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Anti-Inflammatory Effects of Plasma Circulating Exosomes Obtained from Normal-Weight and Obese Subjects on Hepatocytes

Author(s): Reza Afrisham, Sahar Sadegh-Nejadi, Reza Meshkani, Solaleh Emamgholipour, Molood Bagherieh and Maliheh Paknejad*

Volume 21, Issue 3, 2021

Published on: 05 May, 2020

Page: [478 - 484] Pages: 7

DOI: 10.2174/1871530320666200505121426

Price: $65

Abstract

Introduction: Obesity is a disorder with low-grade chronic inflammation that plays a key role in hepatic inflammation and steatosis. Moreover, there are studies to support the role of exosomes in cellular communications, the regulation of metabolic homeostasis and immunomodulatory activity. Accordingly, we aimed to evaluate the influence of plasma circulating exosomes derived from females with normal-weight and obesity on the secretion of inflammatory cytokines in human liver cells.

Methods: Plasma circulating exosomes were isolated from four normal (N-Exo) and four obese (OExo) women. The exosomes were characterized and approved for CD63 expression (common exosomal protein marker) and morphology/size using the western blot and TEM methods, respectively. The exosomes were used for the stimulation of HepG2 cells in vitro. After 24 h of incubation, the protein levels of TNF-α, IL-6, and IL-1β were measured in the culture supernatant of HepG2 cells using the ELISA kit.

Results: The protein levels of IL-6 and TNF-α in the cells treated with O-Exo and N-Exo reduced significantly in comparison with the control group (P=0.039 and P<0.001 respectively), while significant differences were not found between normal and obese groups (P=0.808, and P=0.978 respectively). However, no significant differences were found among the three groups in terms of IL-1β levels (P=0.069). Based on the correlation analysis, the protein levels of IL-6 were positively correlated with TNF-α (r 0.978, P<0.001).

Conclusion: These findings suggest that plasma circulating exosomes have probably antiinflammatory properties independent of body mass index and may decrease the secretion of inflammatory cytokines in the liver. However, further in vitro and in vivo investigations are needed to address the anti-inflammatory function of N-Exo and O-Exo in human liver cells and/or other cells.

Keywords: Exosome, inflammatory cytokines, interleukin-6, liver, tumor necrosis factor-alpha, obesity.

« Previous Next »
Graphical Abstract

[1]
Zhao, H.; Shang, Q.; Pan, Z.; Bai, Y.; Li, Z.; Zhang, H.; Zhang, Q.; Guo, C.; Zhang, L.; Wang, Q. Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissue. Diabetes, 2018, 67(2), 235-247.
[http://dx.doi.org/10.2337/db17-0356] [PMID: 29133512]
[2]
Meshkani, R.; Adeli, K. Hepatic insulin resistance, metabolic syndrome and cardiovascular disease. Clin. Biochem., 2009, 42(13-14), 1331-1346.
[http://dx.doi.org/10.1016/j.clinbiochem.2009.05.018] [PMID: 19501581]
[3]
Kranendonk, M.E.; Visseren, F.L.; van Herwaarden, J.A.; Nolte-’t Hoen, E.N.; de Jager, W.; Wauben, M.H.; Kalkhoven, E. Effect of extracellular vesicles of human adipose tissue on insulin signaling in liver and muscle cells. Obesity (Silver Spring), 2014, 22(10), 2216-2223.
[http://dx.doi.org/10.1002/oby.20847] [PMID: 25045057]
[4]
Shi, H.; Kokoeva, M.V.; Inouye, K.; Tzameli, I.; Yin, H.; Flier, J.S. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest., 2006, 116(11), 3015-3025.
[http://dx.doi.org/10.1172/JCI28898] [PMID: 17053832]
[5]
Verschuren, L.; Kooistra, T.; Bernhagen, J.; Voshol, P.J.; Ouwens, D.M.; van Erk, M.; de Vries-van der Weij, J.; Leng, L.; van Bockel, J.H.; van Dijk, K.W.; Fingerle-Rowson, G.; Bucala, R.; Kleemann, R. MIF deficiency reduces chronic inflammation in white adipose tissue and impairs the development of insulin resistance, glucose intolerance, and associated atherosclerotic disease. Circ. Res., 2009, 105(1), 99-107.
[http://dx.doi.org/10.1161/CIRCRESAHA.109.199166] [PMID: 19478200]
[6]
Kranendonk, M.E.; Visseren, F.L.; van Balkom, B.W.; Nolte-’t Hoen, E.N.; van Herwaarden, J.A.; de Jager, W.; Schipper, H.S.; Brenkman, A.B.; Verhaar, M.C.; Wauben, M.H.; Kalkhoven, E. Human adipocyte extracellular vesicles in reciprocal signaling between adipocytes and macrophages. Obesity (Silver Spring), 2014, 22(5), 1296-1308.
[http://dx.doi.org/10.1002/oby.20679] [PMID: 24339422]
[7]
Helwa, I.; Cai, J.; Drewry, M.D.; Zimmerman, A.; Dinkins, M.B.; Khaled, M.L.; Seremwe, M.; Dismuke, W.M.; Bieberich, E.; Stamer, W.D.; Hamrick, M.W.; Liu, Y. A comparative study of serum exosome isolation using differential ultracentrifugation and three commercial reagents. PLoS One, 2017, 12(1)e0170628
[http://dx.doi.org/10.1371/journal.pone.0170628] [PMID: 28114422]
[8]
Lawson, C.; Vicencio, J.M.; Yellon, D.M.; Davidson, S.M. Microvesicles and exosomes: new players in metabolic and cardiovascular disease. J. Endocrinol., 2016, 228(2), R57-R71.
[http://dx.doi.org/10.1530/JOE-15-0201] [PMID: 26743452]
[9]
Thomou, T.; Mori, M.A.; Dreyfuss, J.M.; Konishi, M.; Sakaguchi, M.; Wolfrum, C.; Rao, T.N.; Winnay, J.N.; Garcia-Martin, R.; Grinspoon, S.K.; Gorden, P.; Kahn, C.R. Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature, 2017, 542(7642), 450-455.
[http://dx.doi.org/10.1038/nature21365] [PMID: 28199304]
[10]
Raposo, G.; Stoorvogel, W. Extracellular vesicles: exosomes, microvesicles, and friends. J. Cell Biol., 2013, 200(4), 373-383.
[http://dx.doi.org/10.1083/jcb.201211138] [PMID: 23420871]
[11]
Luo, Q.; Guo, D.; Liu, G.; Chen, G.; Hang, M.; Jin, M. Exosomes from MiR-126-overexpressing adscs are therapeutic in relieving acute myocardial ischaemic injury. Cell. Physiol. Biochem., 2017, 44(6), 2105-2116.
[http://dx.doi.org/10.1159/000485949] [PMID: 29241208]
[12]
Ti, D.; Hao, H.; Tong, C.; Liu, J.; Dong, L.; Zheng, J.; Zhao, Y.; Liu, H.; Fu, X.; Han, W. LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b. J. Transl. Med., 2015, 13(1), 308.
[http://dx.doi.org/10.1186/s12967-015-0642-6] [PMID: 26386558]
[13]
Li, R.; Liang, P.; Yuan, J.; He, F. Exosomal miR-103a-3p ameliorates LPS-induced immune response in BEAS-2B cells via NF-κB pathway by targeting TBL1XR1. Clin. Exp. Pharmacol. Physiol., 2019.
[14]
Tamura, R.; Uemoto, S.; Tabata, Y. Immunosuppressive effect of mesenchymal stem cell-derived exosomes on a concanavalin A-induced liver injury model. Inflamm. Regen., 2016, 36(1), 26.
[http://dx.doi.org/10.1186/s41232-016-0030-5] [PMID: 29259699]
[15]
Zheng, L.; Li, Z.; Ling, W.; Zhu, D.; Feng, Z.; Kong, L. Exosomes derived from dendritic cells attenuate liver injury by modulating the balance of treg and Th17 cells after ischemia reperfusion. Cell. Physiol. Biochem., 2018, 46(2), 740-756.
[http://dx.doi.org/10.1159/000488733] [PMID: 29621784]
[16]
Romanelli, P.; Bieler, L.; Scharler, C.; Pachler, K.; Kreutzer, C.; Zaunmair, P.; Jakubecova, D.; Mrowetz, H.; Benedetti, B.; Rivera, F.J.; Aigner, L.; Rohde, E.; Gimona, M.; Strunk, D.; Couillard-Despres, S. Extracellular Vesicles Can Deliver Anti-inflammatory and Anti-scarring Activities of Mesenchymal Stromal Cells After Spinal Cord Injury. Front. Neurol., 2019, 10, 1225.
[http://dx.doi.org/10.3389/fneur.2019.01225] [PMID: 31849808]
[17]
Huang, J-H.; Yin, X-M.; Xu, Y.; Xu, C-C.; Lin, X.; Ye, F-B.; Cao, Y.; Lin, F.Y. Systemic administration of exosomes released from mesenchymal stromal cells attenuates apoptosis, inflammation, and promotes angiogenesis after spinal cord injury in rats. J. Neurotrauma, 2017, 34(24), 3388-3396.
[http://dx.doi.org/10.1089/neu.2017.5063] [PMID: 28665182]
[18]
Casado, J.G.; Blázquez, R.; Vela, F.J.; Álvarez, V.; Tarazona, R.; Sánchez-Margallo, F.M. Mesenchymal stem cell-derived exosomes: immunomodulatory evaluation in an antigen-induced synovitis porcine model. Front. Vet. Sci., 2017, 4, 39.
[http://dx.doi.org/10.3389/fvets.2017.00039] [PMID: 28377922]
[19]
Jiang, M.; Wang, H.; Jin, M.; Yang, X.; Ji, H.; Jiang, Y.; Zhang, H.; Wu, F.; Wu, G.; Lai, X.; Cai, L.; Hu, R.; Xu, L.; Li, L. Exosomes from MiR-30d-5p-ADSCs reverse acute ischemic stroke-induced, autophagy-mediated brain injury by promoting M2 microglial/macrophage polarization. Cell. Physiol. Biochem., 2018, 47(2), 864-878.
[http://dx.doi.org/10.1159/000490078] [PMID: 29807362]
[20]
Ma, Z.J.; Wang, Y.H.; Li, Z.G.; Wang, Y.; Li, B.Y.; Kang, H.Y.; Wu, X.Y. Immunosuppressive Effect of Exosomes from Mesenchymal Stromal Cells in Defined Medium on Experimental Colitis. Int. J. Stem Cells, 2019, 12(3), 440-448.
[http://dx.doi.org/10.15283/ijsc18139] [PMID: 31242720]
[21]
Geiger, A.; Walker, A.; Nissen, E. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice. Biochem. Biophys. Res. Commun., 2015, 467(2), 303-309.
[http://dx.doi.org/10.1016/j.bbrc.2015.09.166] [PMID: 26454169]
[22]
Wang, N.; Ma, J.; Ren, Y.; Xiang, S.; Jia, R. Secreted klotho from exosomes alleviates inflammation and apoptosis in acute pancreatitis. Am. J. Transl. Res., 2019, 11(6), 3375-3383.
[PMID: 31312351]
[23]
Singla, D.K.; Johnson, T.A.; Tavakoli Dargani, Z. Exosome Treatment Enhances Anti-Inflammatory M2 Macrophages and Reduces Inflammation-Induced Pyroptosis in Doxorubicin-Induced Cardiomyopathy. Cells, 2019, 8(10), 1224.
[http://dx.doi.org/10.3390/cells8101224] [PMID: 31600901]
[24]
Cao, L.; Xu, H.; Wang, G.; Liu, M.; Tian, D.; Yuan, Z. Extracellular vesicles derived from bone marrow mesenchymal stem cells attenuate dextran sodium sulfate-induced ulcerative colitis by promoting M2 macrophage polarization. Int. Immunopharmacol., 2019, 72, 264-274.
[http://dx.doi.org/10.1016/j.intimp.2019.04.020] [PMID: 31005036]
[25]
Chang, C-L.; Chen, C-H.; Chiang, J.Y.; Sun, C-K.; Chen, Y-L.; Chen, K-H.; Sung, P.H.; Huang, T.H.; Li, Y.C.; Chen, H.H.; Yip, H.K. Synergistic effect of combined melatonin and adipose-derived mesenchymal stem cell (ADMSC)-derived exosomes on amelioration of dextran sulfate sodium (DSS)-induced acute colitis. Am. J. Transl. Res., 2019, 11(5), 2706-2724.
[PMID: 31217848]
[26]
Conforti, A.; Scarsella, M.; Starc, N.; Giorda, E.; Biagini, S.; Proia, A.; Carsetti, R.; Locatelli, F.; Bernardo, M.E. Microvescicles derived from mesenchymal stromal cells are not as effective as their cellular counterpart in the ability to modulate immune responses in vitro. Stem Cells Dev., 2014, 23(21), 2591-2599.
[http://dx.doi.org/10.1089/scd.2014.0091] [PMID: 24937591]
[27]
Gouveia de Andrade, A.V.; Bertolino, G.; Riewaldt, J.; Bieback, K.; Karbanová, J.; Odendahl, M.; Bornhäuser, M.; Schmitz, M.; Corbeil, D.; Tonn, T. Extracellular vesicles secreted by bone marrow- and adipose tissue-derived mesenchymal stromal cells fail to suppress lymphocyte proliferation. Stem Cells Dev., 2015, 24(11), 1374-1376.
[http://dx.doi.org/10.1089/scd.2014.0563] [PMID: 25779336]
[28]
Chen, W.; Huang, Y.; Han, J.; Yu, L.; Li, Y.; Lu, Z.; Li, H.; Liu, Z.; Shi, C.; Duan, F.; Xiao, Y. Immunomodulatory effects of mesenchymal stromal cells-derived exosome. Immunol. Res., 2016, 64(4), 831-840.
[http://dx.doi.org/10.1007/s12026-016-8798-6] [PMID: 27115513]
[29]
Del Fattore, A.; Luciano, R.; Pascucci, L.; Goffredo, B.M.; Giorda, E.; Scapaticci, M.; Fierabracci, A.; Muraca, M. Immunoregulatory effects of mesenchymal stem cell-derived extracellular vesicles on T lymphocytes. Cell Transplant., 2015, 24(12), 2615-2627.
[http://dx.doi.org/10.3727/096368915X687543] [PMID: 25695896]
[30]
Ferrante, S.C.; Nadler, E.P.; Pillai, D.K.; Hubal, M.J.; Wang, Z.; Wang, J.M.; Gordish-Dressman, H.; Koeck, E.; Sevilla, S.; Wiles, A.A.; Freishtat, R.J. Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease. Pediatr. Res., 2015, 77(3), 447-454.
[http://dx.doi.org/10.1038/pr.2014.202] [PMID: 25518011]
[31]
Hubal, M.J.; Nadler, E.P.; Ferrante, S.C.; Barberio, M.D.; Suh, J.H.; Wang, J.; Dohm, G.L.; Pories, W.J.; Mietus-Snyder, M.; Freishtat, R.J. Circulating adipocyte-derived exosomal MicroRNAs associated with decreased insulin resistance after gastric bypass. Obesity (Silver Spring), 2017, 25(1), 102-110.
[http://dx.doi.org/10.1002/oby.21709] [PMID: 27883272]
[32]
Mleczko, J.; Ortega, F.J.; Falcon-Perez, J.M.; Wabitsch, M.; Fernandez-Real, J.M.; Mora, S. Extracellular Vesicles from Hypoxic Adipocytes and Obese Subjects Reduce Insulin-Stimulated Glucose Uptake. Mol. Nutr. Food Res., 2018, 62(5)1700917
[http://dx.doi.org/10.1002/mnfr.201700917] [PMID: 29292863]
[33]
Razmkhah, F.; Soleimani, M.; Mehrabani, D.; Karimi, M.H.; Kafi-Abad, S.A. Leukemia cell microvesicles promote survival in umbilical cord blood hematopoietic stem cells. EXCLI J., 2015, 14, 423-429.
[PMID: 26862318]
[34]
Caradec, J.; Kharmate, G.; Hosseini-Beheshti, E.; Adomat, H.; Gleave, M.; Guns, E. Reproducibility and efficiency of serum-derived exosome extraction methods. Clin. Biochem., 2014, 47(13-14), 1286-1292.
[http://dx.doi.org/10.1016/j.clinbiochem.2014.06.011] [PMID: 24956264]
[35]
Shiue, S-J.; Rau, R-H.; Shiue, H-S.; Hung, Y-W.; Li, Z-X.; Yang, K.D.; Cheng, J.K. Mesenchymal stem cell exosomes as a cell-free therapy for nerve injury-induced pain in rats. Pain, 2019, 160(1), 210-223.
[http://dx.doi.org/10.1097/j.pain.0000000000001395] [PMID: 30188455]
[36]
Kornek, M.; Popov, Y.; Libermann, T.A.; Afdhal, N.H.; Schuppan, D. Human T cell microparticles circulate in blood of hepatitis patients and induce fibrolytic activation of hepatic stellate cells. Hepatology, 2011, 53(1), 230-242.
[http://dx.doi.org/10.1002/hep.23999] [PMID: 20979056]
[37]
Alexander, M.; Hu, R.; Runtsch, M.C.; Kagele, D.A.; Mosbruger, T.L.; Tolmachova, T.; Seabra, M.C.; Round, J.L.; Ward, D.M.; O’Connell, R.M. Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat. Commun., 2015, 6, 7321.
[http://dx.doi.org/10.1038/ncomms8321] [PMID: 26084661]
[38]
Yang, C.; Lim, W.; Park, J.; Park, S.; You, S.; Song, G. Anti-inflammatory effects of mesenchymal stem cell-derived exosomal microRNA-146a-5p and microRNA-548e-5p on human trophoblast cells. Mol. Hum. Reprod., 2019, 25(11), 755-771.
[http://dx.doi.org/10.1093/molehr/gaz054] [PMID: 31588496]
[39]
Ouchi, N.; Walsh, K. A novel role for adiponectin in the regulation of inflammation; Am Heart Assoc, 2008.
[http://dx.doi.org/10.1161/ATVBAHA.108.165068]
[40]
Phoonsawat, W.; Aoki-Yoshida, A.; Tsuruta, T.; Sonoyama, K. Adiponectin is partially associated with exosomes in mouse serum. Biochem. Biophys. Res. Commun., 2014, 448(3), 261-266.
[http://dx.doi.org/10.1016/j.bbrc.2014.04.114] [PMID: 24792183]
[41]
Deng, Z.B.; Poliakov, A.; Hardy, R.W.; Clements, R.; Liu, C.; Liu, Y.; Wang, J.; Xiang, X.; Zhang, S.; Zhuang, X.; Shah, S.V.; Sun, D.; Michalek, S.; Grizzle, W.E.; Garvey, T.; Mobley, J.; Zhang, H.G. Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes, 2009, 58(11), 2498-2505.
[http://dx.doi.org/10.2337/db09-0216] [PMID: 19675137]
[42]
Wang, L.; Zhang, B.; Zheng, W.; Kang, M.; Chen, Q.; Qin, W.; Li, C.; Zhang, Y.; Shao, Y.; Wu, Y. Exosomes derived from pancreatic cancer cells induce insulin resistance in C2C12 myotube cells through the PI3K/Akt/FoxO1 pathway. Sci. Rep., 2017, 7(1), 5384.
[http://dx.doi.org/10.1038/s41598-017-05541-4 ] [PMID: 28710412]

Rights & Permissions Print Cite
Article Metrics
14
1
© 2024 Bentham Science Publishers | Privacy Policy