Journal of Veterinary Science

The Korean Society of Veterinary Science (대한수의학회)
권호 표지
DOI QR코드

DOI QR Code

MicroRNA-127 promotes antimicrobial ability in porcine alveolar macrophages via S1PR3/TLR signaling pathway

  • Honglei Zhou (School of Pet Science and Technology, Jiangsu Agri-animal Husbandry Vocational College) ;
  • Yujia Qian (Taizhou Jianyouda Pharma Co., LTD) ;
  • Jing Liu (School of Pet Science and Technology, Jiangsu Agri-animal Husbandry Vocational College)
  • Received : 2022.04.20
  • Accepted : 2022.12.16
  • Published : 2023.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Background: As Actinobacillus pleuropneumonniae (APP) infection causes considerable losses in the pig industry, there is a growing need to develop effective therapeutic interventions that leverage host immune defense mechanisms to combat these pathogens. Objectives: To demonstrate the role of microRNA (miR)-127 in controlling bacterial infection against APP. Moreover, to investigate a signaling pathway in macrophages that controls the production of anti-microbial peptides. Methods: Firstly, we evaluated the effect of miR-127 on APP-infected pigs by cell count/enzyme-linked immunosorbent assay (ELISA). Then the impact of miR-127 on immune cells was detected. The cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 were evaluated by ELISA. The expression of cytokines (anti-microbial peptides [AMPs]) was assessed using quantitative polymerase chain reaction. The expression level of IL-6, TNF-α and p-P65 were analyzed by western blot. The expression of p65 in the immune cells was investigated by immunofluorescence. Results: miR-127 showed a protective effect on APP-infected macrophage. Moreover, the protective effect might depend on its regulation of macrophage bactericidal activity and the generation of IL-22, IL-17 and AMPs by targeting sphingosine-1-phosphate receptor3 (SIPR3), the element involved in the Toll-like receptor (TLR) cascades. Conclusions: Together, we identify that miR-127 is a regulator of S1PR3 and then regulates TLR/nuclear factor-κB signaling in macrophages with anti-bacterial acticity, and it might be a potential target for treating inflammatory diseases caused by APP.

Keywords

Acknowledgement

This work was supported by National Double High Program: Animal Husbandry and Veterinary medicine Subject group; college program of Jiangsu Agri-animal Husbandry Vocational College (NSF201903).

References

  1. Hathroubi S, Beaudry F, Provost C, Martelet L, Segura M, Gagnon CA, et al. Impact of Actinobacillus pleuropneumoniae biofilm mode of growth on the lipid A structures and stimulation of immune cells. Innate Immun. 2016;22(5):353-362.  https://doi.org/10.1177/1753425916649676
  2. Hsu CW, Li SC, Chang NY, Chen ZW, Liao JW, Chen TH, et al. Involvement of NF-κB in regulation of Actinobacillus pleuropneumoniae exotoxin ApxI-induced proinflammatory cytokine production in porcine alveolar macrophages. Vet Microbiol. 2016;195:128-135.  https://doi.org/10.1016/j.vetmic.2016.09.020
  3. Xiong J, Zhu Q, Yang S, Zhao Y, Cui L, Zhuang F, et al. Comparison of pharmacokinetics of tilmicosin in healthy pigs and pigs experimentally infected with Actinobacillus pleuropneumoniae. N Z Vet J. 2019;67(5):257-263.  https://doi.org/10.1080/00480169.2019.1633434
  4. Mortensen S, Skovgaard K, Hedegaard J, Bendixen C, Heegaard PM. Transcriptional profiling at different sites in lungs of pigs during acute bacterial respiratory infection. Innate Immun. 2011;17(1):41-53. https://doi.org/10.1177/1753425909349760
  5. Tsiotou AG, Sakorafas GH, Anagnostopoulos G, Bramis J. Septic shock; current pathogenetic concepts from a clinical perspective. Med Sci Monit. 2005;11(3):RA76-RA85. 
  6. Kennedy DW, Abkowitz JL. Kinetics of central nervous system microglial and macrophage engraftment: analysis using a transgenic bone marrow transplantation model. Blood. 1997;90(3):986-993.  https://doi.org/10.1182/blood.V90.3.986
  7. Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol. 2009;27(1):451-483.  https://doi.org/10.1146/annurev.immunol.021908.132532
  8. Yi YS. Folate receptor-targeted diagnostics and therapeutics for inflammatory diseases. Immune Netw. 2016;16(6):337-343.  https://doi.org/10.4110/in.2016.16.6.337
  9. Tiwari D, Peariso K, Gross C. MicroRNA-induced silencing in epilepsy: opportunities and challenges for clinical application. Dev Dyn. 2018;247(1):94-110.  https://doi.org/10.1002/dvdy.24582
  10. Chen JJ, Zhao B, Zhao J, Li S. Potential roles of exosomal microRNAs as diagnostic biomarkers and therapeutic application in Alzheimer's disease. Neural Plast. 2017;2017:7027380. 
  11. Song G, Wang L. Transcriptional mechanism for the paired miR-433 and miR-127 genes by nuclear receptors SHP and ERRgamma. Nucleic Acids Res. 2008;36(18):5727-5735.  https://doi.org/10.1093/nar/gkn567
  12. Ying H, Kang Y, Zhang H, Zhao D, Xia J, Lu Z, et al. MiR-127 modulates macrophage polarization and promotes lung inflammation and injury by activating the JNK pathway. J Immunol. 2015;194(3):1239-1251.  https://doi.org/10.4049/jimmunol.1402088
  13. Liu X, Mao Y, Kang Y, He L, Zhu B, Zhang W, et al. MicroRNA-127 promotes anti-microbial host defense through restricting A20-mediated De-ubiquitination of STAT3. iScience. 2020;23(1):100763. 
  14. Zhai L, Wu R, Han W, Zhang Y, Zhu D. miR-127 enhances myogenic cell differentiation by targeting S1PR3. Cell Death Dis. 2017;8(3):e2707-e2707.  https://doi.org/10.1038/cddis.2017.128
  15. Sun X, Ma SF, Wade MS, Acosta-Herrera M, Villar J, Pino-Yanes M, et al. Functional promoter variants in sphingosine 1-phosphate receptor 3 associate with susceptibility to sepsis-associated acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol. 2013;305(7):L467-L477.  https://doi.org/10.1152/ajplung.00010.2013
  16. Bustamante MF, Garcia-Carbonell R, Whisenant KD, Guma M. Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis. Arthritis Res Ther. 2017;19(1):110. 
  17. Thacker EL. Lung inflammatory responses. Vet Res. 2006;37(3):469-486.  https://doi.org/10.1051/vetres:2006011
  18. Huang H, Potter AA, Campos M, Leighton FA, Willson PJ, Haines DM, et al. Pathogenesis of porcine Actinobacillus pleuropneumonia, part II: roles of proinflammatory cytokines. Can J Vet Res. 1999;63(1):69-78. 
  19. Liu X, Mao Y, Kang Y, He L, Zhu B, Zhang W, et al. MicroRNA-127 promotes anti-microbial host defense through restricting A20-mediated de-ubiquitination of STAT3. iScience. 2020;23(1):100763. 
  20. Seeley JJ, Baker RG, Mohamed G, Bruns T, Hayden MS, Deshmukh SD, et al. Induction of innate immune memory via microRNA targeting of chromatin remodelling factors. Nature. 2018;559(7712):114-119.  https://doi.org/10.1038/s41586-018-0253-5
  21. Rothchild AC, Sissons JR, Shafiani S, Plaisier C, Min D, Mai D, et al. MiR-155-regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2016;113(41):E6172-E6181.  https://doi.org/10.1073/pnas.1608255113
  22. Wang Y, Li Y, Zhang P, Baker ST, Wolfson MR, Weiser JN, et al. Regenerative therapy based on miRNA-302 mimics for enhancing host recovery from pneumonia caused by Streptococcus pneumoniae. Proc Natl Acad Sci U S A. 2019;116(17):8493-8498.  https://doi.org/10.1073/pnas.1818522116
  23. El Gazzar M, Church A, Liu T, McCall CE. MicroRNA-146a regulates both transcription silencing and translation disruption of TNF-α during TLR4-induced gene reprogramming. J Leukoc Biol. 2011;90:509-519. https://doi.org/10.1189/jlb.0211074
  24. Suzuki Y, Kim HW, Ashraf M, Haider HK. Diazoxide potentiates mesenchymal stem cell survival via NF-kappaB-dependent miR-146a expression by targeting Fas. Am J Physiol Heart Circ Physiol. 2010;299(4):H1077-H1082.  https://doi.org/10.1152/ajpheart.00212.2010
  25. Nahid MA, Satoh M, Chan EK. Mechanistic role of microRNA-146a in endotoxin-induced differential cross-regulation of TLR signaling. J Immunol. 2011;186(3):1723-1734.  https://doi.org/10.4049/jimmunol.1002311
  26. Rusca N, Monticelli S. MiR-146a in immunity and disease. Mol Biol Int. 2011;2011:437301. 
  27. Lai L, Song Y, Liu Y, Chen Q, Han Q, Chen W, et al. MicroRNA-92a negatively regulates Toll-like receptor (TLR)-triggered inflammatory response in macrophages by targeting MKK4 kinase. J Biol Chem. 2013;288(11):7956-7967.  https://doi.org/10.1074/jbc.M112.445429
  28. Branchett WJ, Lloyd CM. Regulatory cytokine function in the respiratory tract. Mucosal Immunol. 2019;12(3):589-600.  https://doi.org/10.1038/s41385-019-0158-0
  29. Sechet E, Telford E, Bonamy C, Sansonetti PJ, Sperandio B. Natural molecules induce and synergize to boost expression of the human antimicrobial peptide β-defensin-3. Proc Natl Acad Sci U S A. 2018;115(42):E9869-E9878.  https://doi.org/10.1073/pnas.1805298115
  30. Choi SM, McAleer JP, Zheng M, Pociask DA, Kaplan MH, Qin S, et al. Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia. J Exp Med. 2013;210(3):551-561.  https://doi.org/10.1084/jem.20120260
  31. Li J, Casanova JL, Puel A. Mucocutaneous IL-17 immunity in mice and humans: host defense vs. excessive inflammation. Mucosal Immunol. 2018;11(3):581-589.  https://doi.org/10.1038/mi.2017.97
  32. Saint-Criq V, Villeret B, Bastaert F, Kheir S, Hatton A, Cazes A, et al. Pseudomonas aeruginosa LasB protease impairs innate immunity in mice and humans by targeting a lung epithelial cystic fibrosis transmembrane regulator-IL-6-antimicrobial-repair pathway. Thorax. 2018;73(1):49-61.  https://doi.org/10.1136/thoraxjnl-2017-210298
  33. Ruan HH, Zhang Z, Wang SY, Nickels LM, Tian L, Qiao JJ, et al. Tumor necrosis factor receptor-associated factor 6 (TRAF6) mediates ubiquitination-dependent STAT3 activation upon Salmonella enterica serovar Typhimurium infection. Infect Immun. 2017;85(8):85.