TGF-β Targeted by miR-27a Modulates Anti-Parasite Responses of Immune System
-
Faezeh Hamidi
,
Samira Mohammadi -Yeganeh
,
Mostafa Haji Molla Hoseini
,
Seyyed Javad Seyyed Tabaei
,
Niloofar Taghipour
,
Ameneh Koochaki
,
Vahedeh Hosseini
,
Ali Haghighi
Abstract
Background: Immune cells and their secreted cytokines are known as the first barrier against pathogens. Leishmania major as an intracellular protozoan produces anti-inflammatory cytokines that lead to proliferation and survival of the parasite in the macrophages. miRNAs are small non-coding RNA molecules that regulate mRNAs expression. We aimed to investigate the relationship between the expression of TGF-β and a bioinformatically candidate miRNA, in leishmaniasis as a model of TGF-β overexpression.
Methods: The miRNAs that target TGF-β -3´UTR were predicted and scored by bioinformatic tools. After cloning of TGF-β-3'UTR in psi-CHECK TM- 2 vector, targeting validation was confirmed using Luciferase assay. After miRNA mimic transfection, the expression of miR-27a, TGF-β, as well as Nitric Oxide concentration was evaluated.
Results: miR-27a received the highest score for targeting TGF-β in bioinformatic predictions. Luciferase assay confirmed that miR-27a is targeting TGF-β-3'UTR, since miR-27a transfection decreased the luciferase activity. After miRNA transfection, TGF-β expression and Nitric Oxide concentration were declined in L. major infected macrophages.
Conclusion: Bioinformatic prediction, luciferase assay, and miRNA transfection results showed that miR-27a targets TGF-β. Since miRNA and cytokine-base therapies are developing in infectious diseases, finding and validating miRNAs targeting regulatory cytokines can be a novel strategy for controlling and treating leishmaniasis.
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13. Crooke ST. Progress in antisense technology. Annu Rev Med. 2004; 55: 61-95. doi.org//10.1146/annurev.med.55.091902.104408
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17. Xie N, Cui H, Banerjee S, Tan Z, et al. miR-27a regulates inflammatory response of macrophages by targeting IL-10. J Immunol. 2014; 193 (1): 327-34. doi.org/10.4049/jimmunol.1400203
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19. Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. Elife; 2015; 4: e05005.
20. NLM. Samples of Formatted References for Authors of Journal Articles. http://www.nlm.nih.gov/bsd/uniform_requirements.html
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23. Karami F, Mohammadi‐Yeganeh S, et al. Bioinformatics Prediction and In Vitro Analysis Revealed That miR‐17 Targets Cyclin D 1 mRNA in Triple Negative Breast Cancer Cells. Wiley Online Library. 2016; 317-20.
24. Lasjerdi Z, Ghanbarian H, Mohammadi-Yeganeh S, et al. Comparative expression profile analysis of apoptosis-related miRNA and its target gene in Leishmania major infected macrophages. Iran J Parasitol. 2020; 15: 332- 40. doi.org/ 10.18502/ijpa.v15i3.4197
25. Gholamrezaei M, Rouhani S, Mohebali M, et al. MicroRNAs expression induces apoptosis of macrophages in response to Leishmania major (MRHO/IR/75/ER): an in-vitro and in-vivo study. Iran J Parasitol. 2020; 15: 475-87. doi.org/ 10.18502/ijpa.v15i4.4851
26. Guevara I, Iwanejko J, Dembińska-Kieć A, et al. Determination of nitrite/nitrate in human biological material by the simple Griess reaction. Clin Chim Acta. 1998; 274(2); 177-88. doi.org/10.1016/S0009-8981(98)00060-6
27. Ribeiro-Gomes FL, Otero AC, Gomes NA, et al. Macrophage interactions with neutrophils regulate Leishmania major infection. J Immunol. 2004; 172 (7) : 4454-62. doi.org/10.4049/jimmunol.172.7.4454
28. Kane MM, Mosser DM. Leishmania parasites and their ploys to disrupt macrophage activation. Curr Opin Hematol. 2000; 7(1): 6-31.
29. Tahamtan A, Teymoori-Rad M, Nakstad B, Salimi V. Anti-inflammatory microRNAs and their potential for inflammatory diseases treatment. Front Immunol. 2018; 9: 1377. doi.org/10.3389/fimmu.2018.01377
30. Jin Y, Chen Z, Liu X, Zhou X. Evaluating the microRNA targeting sites by luciferase reporter gene assay. Methods Mol Biol. 2013;936:117-27.
31. Sherf BA, Navarro SL, Hannah RR, Wood K. Dual-luciferase reporter assay: an advanced co-reporter technology integrating firefly and Renilla luciferase assays. Promega Notes. 1996; 57 (2): 2-8.
32. Rezaei F, Daryani A, Sharifi M, et al. miR-20a inhibition using locked nucleic acid (LNA) technology and its effects on apoptosis of human macrophages infected by Toxoplasma gondii RH strain. Microb Pathog. 2018; 121: 269-76. doi.org/10.1016/j.micpath.2018.05.030
33. Monteiro CJ, Mota SLA, Diniz LdF, Bahia MT, Moraes K. miR-190b negatively contributes to the Trypanosoma cruzi-infected cell survival by repressing PTEN protein expression. Mem Inst Oswaldo Cruz. 2015; 110: 996-1002. doi.org/10.1590/0074-02760150184
34. Cai Y, Chen H, Mo X, et al. Toxoplasma gondii inhibits apoptosis via a novel STAT3-miR-17–92-Bim pathway in macrophages.Cell Signal. 2014; 26 (6): 1204-12. doi.org/10.1016/j.cellsig.2014.02.013
35. Gong AY, Zhou R, Hu G, et al. Cryptosporidium parvum induces B7-H1 expression in cholangiocytes by down-regulating microRNA-513. J Infect Dis. 2010; 201(1): 160-9. doi.org/10.1086/648589
36. Lin WC, Huang KY, Chen SC, et al. Malate dehydrogenase is negatively regulated by miR-1 in Trichomonas vaginalis. Parasitol Res. 2009; 105 (6) : 1683-9. doi.org/10.1007/s00436-009-1616-5
37. Frank B, Marcu A, Petersen ALdoa, et al. Autophagic digestion of Leishmania major by host macrophages is associated with differential expression of BNIP3, CTSE, and the miRNAs miR-101c, miR-129, and miR-210. Parasites Vectors. 2015; 8: 404. doi.org/10.1186/s13071-015-0974-3
38. Dkhil MA, Al-Quraishy SA, Abdel-Baki A-AS, Delic D, Wunderlich F. Differential miRNA expression in the liver of Balb/c mice protected by vaccination during crisis of Plasmodium chabaudi blood-stage malaria. Front Microbiol. 2017; 7: 2155. doi.org/10.3389/fmicb.2016.02155
39. Emami MM, Yazdi M, Nilforoushzadeh M. Emergence of cutaneous leishmaniasis due to Leishmania major in a new focus of central Iran. Trans R Soc Trop Med Hyg. 2009; 103(12): 1257-62. doi.org/10.1016/j.trstmh.2009.04.020
40. Cong W, Zhang XX, He JJ, Li F-C, Elsheikha HM, Zhu X-Q. Global miRNA expression profiling of domestic cat livers following acute Toxoplasma gondii infection. Oncotarget. 2017; 8 (15): 25599-11. doi.org/10.18632/oncotarget.16108
41. Jiang S, Li X, Wang X, Ban Q, Hui W, Jia B. MicroRNA profiling of the intestinal tissue of Kazakh sheep after experimental Echinococcus granulosus infection, using a high-throughput approach. Parasite. 2016; 23: 23. doi.org/ 10.1051/parasite/2016023
42. Han H, Peng J, Hong Y, et al. MicroRNA expression profile in different tissues of BALB/c mice in the early phase of Schistosoma japonicum infection. Mol Biochem Parasitol. 2013; 188 (1): 1-9. doi.org/10.1016/j.molbiopara.2013.02.001
43. Jiang H, Zhai T, Yu Y, et al. Delayed IL-12 production by macrophages during Toxoplasma gondii infection is regulated by miR-187. Parasitol Res. 2020; 119 (3): 1023-33. doi.org/10.1007/s00436-019-06588-0
44. Hamidi F, Mohammadi-Yeganeh S, et al. Inhibition of anti-inflammatory cytokines, IL-10 and TGF-β, in Leishmania major infected macrophages by miRNAs: A new therapeutic modality against leishmaniasis. Microb Pathog. 2021;153. 104777. doi.org/10.1016/j.micpath.2021.104777.
45. Kavoosi G, Ardestani SK, Kariminia A, Tavakoli Z. Production of nitric oxide by murine macrophages induced by lipophosphoglycan of Leishmania major. Korean J Parasitol. 2006; 44 (1): 35-41. doi.org/ 10.3347/kjp.2006.44.1.35
46. Muxel SM, Laranjeira-Silva MF, Zampieri RA, Floeter-Winter LM. Leishmania (Leishmania) amazonensis induces macrophage miR-294 and miR-721 expression and modulates infection by targeting NOS2 and L-arginine metabolism. Sci Rep. 2017; 7(1): 1-15. doi.org/10.1038/srep44141
47. Muxel SM, Acuna SM, Aoki JI, Zampieri RA, Floeter-Winter LM. Toll-like receptor and miRNA-let-7e expression alter the inflammatory response in Leishmania amazonensis-infected macrophages. Front Immunol. 2018; 2792. doi.org/10.3389/fimmu.2018.02792
48. Fernandes JCR, Aoki JI, Maia Acuña S, et al . Melatonin and Leishmania amazonensis infection altered miR-294, miR-30e, and miR-302d impacting on tnf, mcp-1, and nos2 expression. Front Cell Infect Microbiol. 2019; 9: 60. doi.org/10.3389/fcimb.2019.00060
49. Janssen HL, Reesink HW, Lawitz EJ, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med. 2013; 368 (18): 1685-94. doi.org/ 10.1056/NEJMoa1209026
2. Tauber AI. Metchnikoff and the phagocytosis theory. Nat Rev Mol Cell Biol. 2003; 4 (11): 897-901.
3. Liu D, Uzonna JE. The early interaction of Leishmania with macrophages and dendritic cells and its influence on the host immune response. Front Cell Infect Microbiol. 2012; 2:83. doi.org/10.3389/fcimb.2012.00083
4. Barral-Netto M, Barral A, Brownell CE, et al. Transforming growth factor-β in leishmanial infection: a parasite escape mechanism. Science. 1992; 257 (5069): 545-8. doi.org/ 10.1126/science.1636092
5. Abdoli A, Maspi N, Ghaffarifar F. Wound healing in cutaneous leishmaniasis: a double edged sword of IL-10 and TGF-β. Comp Immunol Microbiol Infect Dis. 2017; 51:15-26. doi.org/10.1016/j.cimid.2017.02.001
6. Gantt KR, Schultz-Cherry S, Rodriguez N, et al. Activation of TGF-β by Leishmania chagasi: importance for parasite survival in macrophages. J Immunol. 2003; 170 (5): 2613-20. doi.org/10.4049/jimmunol.170.5.2613
7. Fitzpatrick DR, Bielefeldt-Ohmann H. Transforming growth factor β in infectious disease: always there for the host and the pathogen. Trends Microbiol. 1999; 7 (6): 232-6. doi.org/10.1016/S0966-842X(99)01498-5
8. Cunningham AC. Parasitic adaptive mechanisms in infection by Leishmania. Exp Mol Pathol.2002; 72 (2): 132-41. doi.org/10.1006/exmp.2002.2418
9. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol. 2018; 9: 402. doi.org/10.3389/fendo.2018.00402
10. Rodriguez A, Vigorito E, Clare S, et al. Requirement of bic/microRNA-155 for normal immune function. Science. 2007; 316 (5824): 608-11. doi.org/ 10.1126/science.1139253
11. Taganov KD, Boldin MP, Baltimore D. MicroRNAs and immunity: tiny players in a big field. Immunity. 2007; 26 (2): 133-7. doi.org/10.1016/j.immuni.2007.02.005
12. Mohammadi-Yeganeh S, Paryan M, Mirab Samiee S, et al. Development of a robust, low cost stem-loop real-time quantification PCR technique for miRNA expression analysis. Mol Biol Rep. 2013; 40 (5): 3665-74. doi.org/10.1007/s11033-012-2442-x
13. Crooke ST. Progress in antisense technology. Annu Rev Med. 2004; 55: 61-95. doi.org//10.1146/annurev.med.55.091902.104408
14. Bratkovič T, Glavan G, Strukelj B, Zivin M, Rogelj B. Exploiting microRNAs for cell engineering and therapy. Biotechnol Adv. 2012; 30 (3): 753-65. doi.org/10.1016/j.biotechadv.2012.01.006
15. Sharma AR, Sharma G, Lee SS, Chakraborty C. miRNA‐regulated key components of cytokine signaling pathways and inflammation in rheumatoid arthritis. Med Res Rev. 2016; 36 (3): 425-39. doi.org/10.1002/med.21384
16. Tomasello L, Cluts L, Croce CM. Experimental validation of microRNA Targets: Luciferase reporter assay. Methods Mol Biol. 2019;1970:315-330..
17. Xie N, Cui H, Banerjee S, Tan Z, et al. miR-27a regulates inflammatory response of macrophages by targeting IL-10. J Immunol. 2014; 193 (1): 327-34. doi.org/10.4049/jimmunol.1400203
18. Dweep H, Gretz N. miRWalk2. 0: a comprehensive atlas of microRNA-target interactions. Nat Methods. 2015; 12 (8): 697. doi.org/10.1038/nmeth.3485
19. Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. Elife; 2015; 4: e05005.
20. NLM. Samples of Formatted References for Authors of Journal Articles. http://www.nlm.nih.gov/bsd/uniform_requirements.html
21. "Improved TA Cloning". Caister Academic Press. Archived from the original on 2011-07-08. Retrieved 2009-10-17.
22. Application for the psiCHECK™-2 Vector. microRNA Biosensors. www.promega.com. Number 99 may 2008.
23. Karami F, Mohammadi‐Yeganeh S, et al. Bioinformatics Prediction and In Vitro Analysis Revealed That miR‐17 Targets Cyclin D 1 mRNA in Triple Negative Breast Cancer Cells. Wiley Online Library. 2016; 317-20.
24. Lasjerdi Z, Ghanbarian H, Mohammadi-Yeganeh S, et al. Comparative expression profile analysis of apoptosis-related miRNA and its target gene in Leishmania major infected macrophages. Iran J Parasitol. 2020; 15: 332- 40. doi.org/ 10.18502/ijpa.v15i3.4197
25. Gholamrezaei M, Rouhani S, Mohebali M, et al. MicroRNAs expression induces apoptosis of macrophages in response to Leishmania major (MRHO/IR/75/ER): an in-vitro and in-vivo study. Iran J Parasitol. 2020; 15: 475-87. doi.org/ 10.18502/ijpa.v15i4.4851
26. Guevara I, Iwanejko J, Dembińska-Kieć A, et al. Determination of nitrite/nitrate in human biological material by the simple Griess reaction. Clin Chim Acta. 1998; 274(2); 177-88. doi.org/10.1016/S0009-8981(98)00060-6
27. Ribeiro-Gomes FL, Otero AC, Gomes NA, et al. Macrophage interactions with neutrophils regulate Leishmania major infection. J Immunol. 2004; 172 (7) : 4454-62. doi.org/10.4049/jimmunol.172.7.4454
28. Kane MM, Mosser DM. Leishmania parasites and their ploys to disrupt macrophage activation. Curr Opin Hematol. 2000; 7(1): 6-31.
29. Tahamtan A, Teymoori-Rad M, Nakstad B, Salimi V. Anti-inflammatory microRNAs and their potential for inflammatory diseases treatment. Front Immunol. 2018; 9: 1377. doi.org/10.3389/fimmu.2018.01377
30. Jin Y, Chen Z, Liu X, Zhou X. Evaluating the microRNA targeting sites by luciferase reporter gene assay. Methods Mol Biol. 2013;936:117-27.
31. Sherf BA, Navarro SL, Hannah RR, Wood K. Dual-luciferase reporter assay: an advanced co-reporter technology integrating firefly and Renilla luciferase assays. Promega Notes. 1996; 57 (2): 2-8.
32. Rezaei F, Daryani A, Sharifi M, et al. miR-20a inhibition using locked nucleic acid (LNA) technology and its effects on apoptosis of human macrophages infected by Toxoplasma gondii RH strain. Microb Pathog. 2018; 121: 269-76. doi.org/10.1016/j.micpath.2018.05.030
33. Monteiro CJ, Mota SLA, Diniz LdF, Bahia MT, Moraes K. miR-190b negatively contributes to the Trypanosoma cruzi-infected cell survival by repressing PTEN protein expression. Mem Inst Oswaldo Cruz. 2015; 110: 996-1002. doi.org/10.1590/0074-02760150184
34. Cai Y, Chen H, Mo X, et al. Toxoplasma gondii inhibits apoptosis via a novel STAT3-miR-17–92-Bim pathway in macrophages.Cell Signal. 2014; 26 (6): 1204-12. doi.org/10.1016/j.cellsig.2014.02.013
35. Gong AY, Zhou R, Hu G, et al. Cryptosporidium parvum induces B7-H1 expression in cholangiocytes by down-regulating microRNA-513. J Infect Dis. 2010; 201(1): 160-9. doi.org/10.1086/648589
36. Lin WC, Huang KY, Chen SC, et al. Malate dehydrogenase is negatively regulated by miR-1 in Trichomonas vaginalis. Parasitol Res. 2009; 105 (6) : 1683-9. doi.org/10.1007/s00436-009-1616-5
37. Frank B, Marcu A, Petersen ALdoa, et al. Autophagic digestion of Leishmania major by host macrophages is associated with differential expression of BNIP3, CTSE, and the miRNAs miR-101c, miR-129, and miR-210. Parasites Vectors. 2015; 8: 404. doi.org/10.1186/s13071-015-0974-3
38. Dkhil MA, Al-Quraishy SA, Abdel-Baki A-AS, Delic D, Wunderlich F. Differential miRNA expression in the liver of Balb/c mice protected by vaccination during crisis of Plasmodium chabaudi blood-stage malaria. Front Microbiol. 2017; 7: 2155. doi.org/10.3389/fmicb.2016.02155
39. Emami MM, Yazdi M, Nilforoushzadeh M. Emergence of cutaneous leishmaniasis due to Leishmania major in a new focus of central Iran. Trans R Soc Trop Med Hyg. 2009; 103(12): 1257-62. doi.org/10.1016/j.trstmh.2009.04.020
40. Cong W, Zhang XX, He JJ, Li F-C, Elsheikha HM, Zhu X-Q. Global miRNA expression profiling of domestic cat livers following acute Toxoplasma gondii infection. Oncotarget. 2017; 8 (15): 25599-11. doi.org/10.18632/oncotarget.16108
41. Jiang S, Li X, Wang X, Ban Q, Hui W, Jia B. MicroRNA profiling of the intestinal tissue of Kazakh sheep after experimental Echinococcus granulosus infection, using a high-throughput approach. Parasite. 2016; 23: 23. doi.org/ 10.1051/parasite/2016023
42. Han H, Peng J, Hong Y, et al. MicroRNA expression profile in different tissues of BALB/c mice in the early phase of Schistosoma japonicum infection. Mol Biochem Parasitol. 2013; 188 (1): 1-9. doi.org/10.1016/j.molbiopara.2013.02.001
43. Jiang H, Zhai T, Yu Y, et al. Delayed IL-12 production by macrophages during Toxoplasma gondii infection is regulated by miR-187. Parasitol Res. 2020; 119 (3): 1023-33. doi.org/10.1007/s00436-019-06588-0
44. Hamidi F, Mohammadi-Yeganeh S, et al. Inhibition of anti-inflammatory cytokines, IL-10 and TGF-β, in Leishmania major infected macrophages by miRNAs: A new therapeutic modality against leishmaniasis. Microb Pathog. 2021;153. 104777. doi.org/10.1016/j.micpath.2021.104777.
45. Kavoosi G, Ardestani SK, Kariminia A, Tavakoli Z. Production of nitric oxide by murine macrophages induced by lipophosphoglycan of Leishmania major. Korean J Parasitol. 2006; 44 (1): 35-41. doi.org/ 10.3347/kjp.2006.44.1.35
46. Muxel SM, Laranjeira-Silva MF, Zampieri RA, Floeter-Winter LM. Leishmania (Leishmania) amazonensis induces macrophage miR-294 and miR-721 expression and modulates infection by targeting NOS2 and L-arginine metabolism. Sci Rep. 2017; 7(1): 1-15. doi.org/10.1038/srep44141
47. Muxel SM, Acuna SM, Aoki JI, Zampieri RA, Floeter-Winter LM. Toll-like receptor and miRNA-let-7e expression alter the inflammatory response in Leishmania amazonensis-infected macrophages. Front Immunol. 2018; 2792. doi.org/10.3389/fimmu.2018.02792
48. Fernandes JCR, Aoki JI, Maia Acuña S, et al . Melatonin and Leishmania amazonensis infection altered miR-294, miR-30e, and miR-302d impacting on tnf, mcp-1, and nos2 expression. Front Cell Infect Microbiol. 2019; 9: 60. doi.org/10.3389/fcimb.2019.00060
49. Janssen HL, Reesink HW, Lawitz EJ, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med. 2013; 368 (18): 1685-94. doi.org/ 10.1056/NEJMoa1209026
| Files | ||
| Issue | Vol 18 No 3 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v18i3.13762 | |
| Keywords | ||
| Leishmania major Luciferase assay Immunity | ||
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How to Cite
1.
Hamidi F, Mohammadi -Yeganeh S, Haji Molla Hoseini M, Seyyed Tabaei SJ, Taghipour N, Koochaki A, Hosseini V, Haghighi A. TGF-β Targeted by miR-27a Modulates Anti-Parasite Responses of Immune System. Iran J Parasitol. 2023;18(3):390-399.
