Generic placeholder image

Combinatorial Chemistry & High Throughput Screening


ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

MicroRNA-96 is Downregulated in Sepsis Neonates and Attenuates LPSInduced Inflammatory Response by Inhibiting IL-16 in Monocytes

Author(s): Chunlei Zhang, Xiuting Li, Na Liu, Zijian Feng and Chengyuan Zhang*

Volume 25, Issue 1, 2022

Published on: 10 December, 2020

Page: [90 - 96] Pages: 7

DOI: 10.2174/1386207323666201211091312

Price: $65


Background: Neonatal sepsis (NS) remains one of the leading causes of mortality among newborns. This study found the deregulated microRNA-96 (miR-96) in NS neonates, and aimed to evaluate the clinical significance of miR-96, as well as its effect on LPS-induced inflammatory response in monocytes. In addition, the relationship of interleukin-16 (IL-16) and miR-96 was investigated to understand the underlying mechanisms.

Methods: Expression of miR-96 was examined using real-time quantitative PCR. Monocytes stimulated by LPS was used to mimic excessive inflammation in the pathogenesis of NS. The enzyme-linked immunosorbent assay was applied to evaluate pro-inflammatory cytokine levels. A luciferase reporter assay was used to confirm the interaction between miR-96 and IL-16.

Results: Serum miR-96 expression was decreased in NS newborns and had considerable diagnostic value for NS screening. LPS inhibited miR-96 expression in monocytes, and the overexpression of miR-96 could reverse the effects of LPS on the inflammation of monocytes. IL-16 was a target gene of miR-96 and negatively correlated with miR-96 levels in NS neonates. The inhibited inflammatory responses induced by miR-96 overexpression was abolished by the elevated IL-16 in monocytes.

Conclusion: All the data reveal that serum decreased miR-96 may serve as a candidate noninvasive biomarker for NS diagnosis. In addition, miR-96 inhibits LPS-induced inflammatory responses by targeting IL-16 in monocytes. The miR-96/IL-16 axis may provide novel therapeutic targets for NS treatment.

Keywords: MicroRNA-96, neonatal sepsis, diagnosis, inflammation, monocyte, interleukin-16.

« Previous
Graphical Abstract
Rello, J.; Valenzuela-Sánchez, F.; Ruiz-Rodriguez, M.; Moyano, S. Sepsis: A review of advances in management. Adv. Ther., 2017, 34(11), 2393-2411.
[] [PMID: 29022217]
Shane, A.L.; Sánchez, P.J.; Stoll, B.J. Neonatal sepsis. Lancet, 2017, 390(10104), 1770-1780.
[] [PMID: 28434651]
Li, Y.; Ke, J.; Peng, C.; Wu, F.; Song, Y. microRNA-300/NAMPT regulates inflammatory responses through activation of AMPK/mTOR signaling pathway in neonatal sepsis. Biomed. Pharmacother., 2018, 108, 271-279.
[] [PMID: 30223098]
Wynn, J.L. Defining neonatal sepsis. Curr. Opin. Pediatr., 2016, 28(2), 135-140.
[] [PMID: 26766602]
Richter, D.C.; Heininger, A.; Brenner, T.; Hochreiter, M.; Bernhard, M.; Briegel, J.; Dubler, S.; Grabein, B.; Hecker, A.; Krüger, W.A.; Mayer, K.; Pletz, M.W.; Störzinger, D.; Pinder, N.; Hoppe-Tichy, T.; Weiterer, S.; Zimmermann, S.; Brinkmann, A.; Weigand, M.A.; Lichtenstern, C. Bacterial sepsis: Diagnostics and calculated antibiotic therapy. Anaesthesist, 2017, 66(10), 737-761.
[] [PMID: 28980026]
Sharma, D.; Farahbakhsh, N.; Shastri, S.; Sharma, P. Biomarkers for diagnosis of neonatal sepsis: a literature review. J. Matern. Fetal Neonatal Med., 2018, 31(12), 1646-1659.
[] [PMID: 28427289]
Ni, J.; Zhao, Y.; Su, J.; Liu, Z.; Fang, S.; Li, L.; Deng, J.; Fan, G. Toddalolactone protects lipopolysaccharide-induced sepsis and attenuates lipopolysaccharide-induced inflammatory response by modulating HMGB1-NF-κB translocation. Front. Pharmacol., 2020, 11, 109.
[] [PMID: 32153412]
Rennert, K.; Heisig, K.; Groeger, M.; Wallert, M.; Funke, H.; Lorkowski, S.; Huber, O.; Mosig, A.S. Recruitment of CD16(+) monocytes to endothelial cells in response to LPS-treatment and concomitant TNF release is regulated by CX3CR1 and interfered by soluble fractalkine. Cytokine, 2016, 83, 41-52.
[] [PMID: 27031442]
Askar, B.; Ibrahim, H.; Barrow, P.; Foster, N. Vasoactive intestinal peptide (VIP) differentially affects inflammatory immune responses in human monocytes infected with viable Salmonella or stimulated with LPS. Peptides, 2015, 71, 188-195.
[] [PMID: 26206287]
Zhang, D.; Wang, Y.; Xia, Y.; Huo, J.; Zhang, Y.; Yang, P.; Zhang, Y.; Wang, X. Repression of miR-142-3p alleviates psoriasis-like inflammation by repressing proliferation and promoting apoptosis of keratinocytes via targeting Sema3A. Mol. Cell. Probes, 2020, 52.
[] [PMID: 32325105]
Chen, C.; Tian, A.; Zhou, H.; Zhang, X.; Liu, Z.; Ma, X. Upregulation of miR-211 promotes chondrosarcoma development via targeting tumor suppressor VHL. OncoTargets Ther., 2020, 13, 2935-2943.
[] [PMID: 32308426]
Wang, S.; Wu, Y.; Yang, S.; Liu, X.; Lu, Y.; Liu, F.; Li, G.; Tian, G. miR-874 directly targets AQP3 to inhibit cell proliferation, mobility and EMT in non-small cell lung cancer. Thorac. Cancer, 2020, 11(6), 1550-1558.
[] [PMID: 32301290]
Nejad, C.; Stunden, H.J.; Gantier, M.P. A guide to miRNAs in inflammation and innate immune responses. FEBS J., 2018, 285(20), 3695-3716.
[] [PMID: 29688631]
Zhang, W.; Lu, F.; Xie, Y.; Lin, Y.; Zhao, T.; Tao, S.; Lai, Z.; Wei, N.; Yang, R.; Shao, Y.; He, J. miR-23b negatively regulates sepsis-induced inflammatory responses by targeting ADAM10 in human THP-1 monocytes. Mediators Inflamm., 2019, 20195306541
[] [PMID: 31780861]
Zhu, C.; Chen, T.; Liu, B. Inhibitory effects of miR-25 targeting HMGB1 on macrophage secretion of inflammatory cytokines in sepsis. Oncol. Lett., 2018, 16(4), 5027-5033.
[] [PMID: 30250569]
Chen, J.; Jiang, S.; Cao, Y.; Yang, Y. Altered miRNAs expression profiles and modulation of immune response genes and proteins during neonatal sepsis. J. Clin. Immunol., 2014, 34(3), 340-348.
[] [PMID: 24668300]
Subspecialty Group of Neonatology Pediatric Society Chinese Medical A. Editorial Board Chinese Journal of Pediatrics. Protocol for diagnosis and treatment of neonatal septicemia. Zhonghua Er Ke Za Zhi, 2003, 41(12), 897-899.
[PMID: 14723808]
Yu, H.R.; Chen, R.F.; Hong, K.C.; Bong, C.N.; Lee, W.I.; Kuo, H.C.; Yang, K.D. IL-12-independent Th1 polarization in human mononuclear cells infected with varicella-zoster virus. Eur. J. Immunol., 2005, 35(12), 3664-3672.
[] [PMID: 16285008]
Lei, K.; Bai, H.; Wei, Z.; Xie, C.; Wang, J.; Li, J.; Chen, Q. The mechanism and function of circular RNAs in human diseases. Exp. Cell Res., 2018, 368(2), 147-158.
[] [PMID: 29730164]
Li, Q.L.; Wu, Y.Y.; Sun, H.M.; Gu, W.J.; Zhang, X.X.; Wang, M.J.; Yan, Y.D.; Hao, C.L.; Ji, W.; Chen, Z.R. The role of miR-29c/B7-H3/Th17 axis in children with Mycoplasma pneumoniae pneumonia. Ital. J. Pediatr., 2019, 45(1), 61.
[] [PMID: 31088519]
Ghorpade, D.S.; Sinha, A.Y.; Holla, S.; Singh, V.; Balaji, K.N. NOD2-nitric oxide-responsive microRNA-146a activates Sonic hedgehog signaling to orchestrate inflammatory responses in murine model of inflammatory bowel disease. J. Biol. Chem., 2013, 288(46), 33037-33048.
[] [PMID: 24092752]
Sheng, B.; Zhao, L.; Zang, X.; Zhen, J.; Chen, W. miR-375 ameliorates sepsis by downregulating miR-21 level via inhibiting JAK2-STAT3 signaling. Biomed. Pharmacother., 2017, 86, 254-261.
[] [PMID: 28006751]
Chen, C.; Zhang, L.; Huang, H.; Liu, S.; Liang, Y.; Xu, L.; Li, S.; Cheng, Y.; Tang, W. Serum miR-126-3p level is down-regulated in sepsis patients. Int. J. Clin. Exp. Pathol., 2018, 11(5), 2605-2612.
[PMID: 31938374]
Benz, F.; Roy, S.; Trautwein, C.; Roderburg, C.; Luedde, T. Circulating MicroRNAs as Biomarkers for Sepsis. Int. J. Mol. Sci., 2016, 17(1)
[] [PMID: 26761003]
Wang, X.; Wang, X.; Liu, X.; Wang, X.; Xu, J.; Hou, S.; Zhang, X.; Ding, Y. miR-15a/16 are upreuglated in the serum of neonatal sepsis patients and inhibit the LPS-induced inflammatory pathway. Int. J. Clin. Exp. Med., 2015, 8(4), 5683-5690.
[PMID: 26131152]
Ning, S.; Liu, H.; Gao, B.; Wei, W.; Yang, A.; Li, J.; Zhang, L. miR-155, miR-96 and miR-99a as potential diagnostic and prognostic tools for the clinical management of hepatocellular carcinoma. Oncol. Lett., 2019, 18(3), 3381-3387.
[] [PMID: 31452818]
Mandal, R.; Hardin, H.; Baus, R.; Rehrauer, W.; Lloyd, R.V. Analysis of miR-96 and miR-133a expression in gastrointestinal neuroendocrine neoplasms. Endocr. Pathol., 2017, 28(4), 345-350.
[] [PMID: 29032398]
Schüller, S.S.; Wisgrill, L.; Herndl, E.; Spittler, A.; Förster-Waldl, E.; Sadeghi, K.; Kramer, B.W.; Berger, A. Pentoxifylline modulates LPS-induced hyperinflammation in monocytes of preterm infants in vitro. Pediatr. Res., 2017, 82(2), 215-225.
[] [PMID: 28288151]
Mathy, N.L.; Scheuer, W.; Lanzendörfer, M.; Honold, K.; Ambrosius, D.; Norley, S.; Kurth, R. Interleukin-16 stimulates the expression and production of pro-inflammatory cytokines by human monocytes. Immunology, 2000, 100(1), 63-69.
[] [PMID: 10809960]
Huang, Y.; Du, K.L.; Guo, P.Y.; Zhao, R.M.; Wang, B.; Zhao, X.L.; Zhang, C.Q. IL-16 regulates macrophage polarization as a target gene of mir-145-3p. Mol. Immunol., 2019, 107, 1-9.
[] [PMID: 30634164]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy