Downregulation of miR‑409‑3p suppresses LPS‑induced inflammation in human bronchial epithelial cells through SOCS3/JAK1/STAT3 signaling: The implication for bronchopneumonia

He,Li; Tian,Lang

doi:10.3892/mmr.2021.11829

Downregulation of miR‑409‑3p suppresses LPS‑induced inflammation in human bronchial epithelial cells through SOCS3/JAK1/STAT3 signaling: The implication for bronchopneumonia

Authors:
- Li He
- Lang Tian
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Affiliations: Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: January 6, 2021 https://doi.org/10.3892/mmr.2021.11829
Article Number: 190

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Abstract

In recent decades, the role of microRNAs (miRs) in the development of pneumonia has been reported by a number of researchers. The present study aimed to investigate the role of miR‑409‑3p in lipopolysaccharide (LPS)‑induced human bronchial epithelial cells and the implication for bronchopneumonia. An in vitro inflammation model was established using LPS‑induced BEAS‑2B cells. Cell apoptosis was determined by flow cytometry. Inflammatory factors were detected by ELISA and reverse transcription‑quantitative PCR. Protein levels of Janus kinase 1 (JAK1)/STAT3 and suppressor of cytokine signaling (SOCS)3 were determined by western blotting. Dual‑luciferase reporter assay was performed to confirm the interaction between miR‑409‑3p and SOCS3. LPS treatment significantly increased miR‑409‑3p expression and decreased the expression levels of SOCS3 in BEAS‑2B cells. Dual‑luciferase reporter assay demonstrated that miR‑409‑3p directly targeted and negatively regulated SOCS3. Inhibition of miR‑409‑3p markedly decreased the levels of TNF‑α, IL‑6 and IL‑1β, and suppressed apoptosis induced by LPS, which was reversed by SOCS3‑knockdown. The inhibition of SOCS3 significantly activated JAK1/STAT3 signaling, as well as enhancing the levels of TNF‑α, IL‑6 and IL‑1β, and promoting apoptosis, which was reversed by the JAK1 inhibitor Tofacitinib. Suppression of miR‑409‑3p improved LPS‑induced inflammation through SOCS3 in LPS‑treated BEAS‑2B cells, and this may be caused by regulating JAK1/STAT3 signaling.

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1	McAllister DA, Liu L, Shi T, Chu Y, Reed C, Burrows J, Adeloye D, Rudan I, Black RE, Campbell H, et al: Global, regional, and national estimates of pneumonia morbidity and mortality in children younger than 5 years between 2000 and 2015: A systematic analysis. Lancet Glob Health. 7:e47–e57. 2019. View Article : Google Scholar : PubMed/NCBI
2	Yu C, Xiang Q and Zhang H: Xianyu decoction attenuates the inflammatory response of human lung bronchial epithelial cell. Biomed Pharmacother. 102:1092–1098. 2018. View Article : Google Scholar : PubMed/NCBI
3	Oumei H, Xuefeng W, Jianping L, Kunling S, Rong M, Zhenze C, Li D, Huimin Y, Lining W, Zhaolan L, et al: Etiology of community-acquired pneumonia in 1500 hospitalized children. J Med Virol. 90:421–428. 2018. View Article : Google Scholar : PubMed/NCBI
4	Garenne M, Ronsmans C and Campbell H: The magnitude of mortality from acute respiratory infection in children under 5 years in developing countries. World Health Stat Q. 45:180–191. 1992.PubMed/NCBI
5	Liu Z, Yu H and Guo Q: MicroRNA 20a promotes inflammation via the nuclear factor κB signaling pathway in pediatric pneumonia. Mol Med Rep. 17:612–617. 2018.PubMed/NCBI
6	Zec SL, Selmanovic K, Andrijic NL, Kadic A, Zecevic L and Zunic L: Evaluation of drug treatment of bronchopneumonia at the pediatric clinic in Sarajevo. Med Arh. 70:177–181. 2016. View Article : Google Scholar
7	Catry B, Govaere JLJ, Devriese L, Laevens H, Haesebrouck F and Kruif AD: Bovine enzootic bronchopneumonia: Prevalence of pathogens and its antimicrobial susceptibility. Vlaams Diergeneeskd Tijdschr. 71:348–354. 2002.
8	Abd-El-Fattah AA, Sadik NAH, Shaker OG and Aboulftouh ML: Differential microRNAs expression in serum of patients with lung cancer, pulmonary tuberculosis, and pneumonia. Cell Biochem Biophys. 67:875–884. 2013. View Article : Google Scholar : PubMed/NCBI
9	Foster PS, Plank M, Collison A, Tay HL, Kaiko GE, Li J, Johnston SL, Hansbro PM, Kumar RK, Yang M, et al: The emerging role of microRNAs in regulating immune and inflammatory responses in the lung. Immunol Rev. 253:198–215. 2013. View Article : Google Scholar : PubMed/NCBI
10	Neudecker V, Yuan X, Bowser JL and Eltzschig HK: MicroRNAs in mucosal inflammation. J Mol Med (Berl). 95 (Suppl 3):935–949. 2017. View Article : Google Scholar : PubMed/NCBI
11	Huang F, Zhang J, Yang D, Zhang Y, Huang J, Yuan Y, Li X and Lu G: MicroRNA expression profile of whole blood is altered in adenovirus-infected pneumonia children. Mediators Inflamm. 2018:23206402018. View Article : Google Scholar : PubMed/NCBI
12	Gomez JC, Dang H, Kanke M, Hagan RS, Mock JR, Kelada SNP, Sethupathy P and Doerschuk CM: Predicted effects of observed changes in the mRNA and microRNA transcriptome of lung neutrophils during S. pneumoniae pneumonia in mice. Sci Rep. 7:112582017. View Article : Google Scholar : PubMed/NCBI
13	Guo J and Cheng Y: MicroRNA-1247 inhibits lipopolysaccharides-induced acute pneumonia in A549 cells via targeting CC chemokine ligand 16. Biomed Pharmacother. 104:60–68. 2018. View Article : Google Scholar : PubMed/NCBI
14	Pan J, Ye Z, Zhang N, Lou T and Cao Z: MicroRNA 217 regulates interstitial pneumonia via IL 6. Biotechnol Biotechnol Equip (7). 1–7. 2018.
15	Fei S, Cao L and Pan L: MicroRNA 3941 targets IGF2 to control LPS induced acute pneumonia in A549 cells. Mol Med Rep. 17:4019–4026. 2018.PubMed/NCBI
16	Huang F, Zhang J, Yang D, Zhang Y, Huang J, Yuan Y, Li X and Lu G: MicroRNA expression profile of whole blood is altered in adenovirus infected pneumonia children. Mediators Inflamm. 2018:23206402018. View Article : Google Scholar : PubMed/NCBI
17	Chi X, Ding B, Zhang L, Zhang J, Wang J and Zhang W: lncRNA GAS5 promotes M1 macrophage polarization via miR-455-5p/SOCS3 pathway in childhood pneumonia. J Cell Physiol. 234:13242–13251. 2019. View Article : Google Scholar : PubMed/NCBI
18	Dhar K, Rakesh K, Pankajakshan D and Agrawal DK: SOCS3 promotor hypermethylation and STAT3-NF-κB interaction downregulate SOCS3 expression in human coronary artery smooth muscle cells. Am J Physiol Heart Circ Physiol. 304:H776–H785. 2013. View Article : Google Scholar : PubMed/NCBI
19	Mishra V, Baranwal V, Mishra RK, Sharma S, Paul B and Pandey AC: Titanium dioxide nanoparticles augment allergic airway inflammation and Socs3 expression via NF-κB pathway in murine model of asthma. Biomaterials. 92:90–102. 2016. View Article : Google Scholar : PubMed/NCBI
20	Liu X, Zhou F, Yang Y, Wang W, Niu L, Zuo D, Li X, Hua H, Zhang B, Kou Y, et al: miR-409-3p and miR-1896 co-operatively participate in IL-17-induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3/STAT3 signaling. Glia. 67:101–112. 2019. View Article : Google Scholar : PubMed/NCBI
21	Xiuxia L and Jie M: Luteolin alleviates LPS induced bronchopneumonia injury in vitro and in vivo by down regulating microRNA 132 expression. Biomed Pharmacother. 106:1641–1649. 2018. View Article : Google Scholar : PubMed/NCBI
22	Kjelgaardpetersen CF, Bayjensen AC, Karsdal MA, Hägglund P and Thudium CS: Anti inflammatory inhibitors targeting Jak and Ikk have an anabolic effect on type II collagen turnover ex vivo. Annals of the Rheumatic Diseases. 75 (Suppl 2):185–186. 2016.
23	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
24	Khalil S, Fabbri E, Santangelo A, Bezzerri V, Cantù C, Di Gennaro G, Finotti A, Ghimenton C, Eccher A, Dechecchi M, et al: miRNA array screening reveals cooperative MGMT-regulation between miR-181d-5p and miR-409-3p in glioblastoma. Oncotarget. 7:28195–28206. 2016. View Article : Google Scholar : PubMed/NCBI
25	Zhang J, Hou W, Jia J, Zhao Y and Zhao B: miR-409-3p regulates cell proliferation and tumor growth by targeting E74-like factor 2 in osteosarcoma. FEBS Open Bio. 7:348–357. 2017. View Article : Google Scholar : PubMed/NCBI
26	Dai Y, Huang YS, Tang M, Lv TY, Hu CX, Tan YH, Xu ZM and Yin YB: Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus. 16:939–946. 2007. View Article : Google Scholar : PubMed/NCBI
27	Navarro F, Gutman D, Meire E, Cáceres M, Rigoutsos I, Bentwich Z and Lieberman J: miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53. Blood. 114:2181–2192. 2009. View Article : Google Scholar : PubMed/NCBI
28	Kim G, Ouzounova M, Quraishi AA, Davis A, Tawakkol N, Clouthier SG, Malik F, Paulson AK, D'Angelo RC, Korkaya S, et al: SOCS3-mediated regulation of inflammatory cytokines in PTEN and p53 inactivated triple negative breast cancer model. Oncogene. 34:671–680. 2015. View Article : Google Scholar : PubMed/NCBI
29	Dai Z, Lu L, Yang Z, Mao Y, Lu J, Li C, Qi W, Chen Y, Yao Y, Li L, et al: Kallikrein-binding protein inhibits LPS-induced TNF-α by upregulating SOCS3 expression. J Cell Biochem. 114:1020–1028. 2013. View Article : Google Scholar : PubMed/NCBI
30	Shien K, Papadimitrakopoulou VA, Ruder D, Behrens C, Shen L, Kalhor N, et al: JAK1/STAT3 activation through a proinflammatory cytokine pathway leads to resistance to molecularly targeted therapy in non small cell lung cancer. Mol Cancer Ther. 16:2234–2245. 2017. View Article : Google Scholar : PubMed/NCBI
31	Ma Y, Tang T, Sheng L, Wang Z, Tao H, Zhang Q, Zhang Y and Qi Z: Aloin suppresses lipopolysaccharide induced inflammation by inhibiting JAK1?STAT1/3 activation and ROS production in RAW264.7 cells. Int J Mol Med. 42:1925–1934. 2018.PubMed/NCBI
32	Andoh A, Shioya M, Nishida A, Bamba S, Tsujikawa T, Kim-Mitsuyama S and Fujiyama Y: Expression of IL-24, an activator of the JAK1/STAT3/SOCS3 cascade, is enhanced in inflammatory bowel disease. J Immunol. 183:687–695. 2009. View Article : Google Scholar : PubMed/NCBI
33	Slattery ML, Lundgreen A, Kadlubar SA, Bondurant KL and Wolff RK: JAK/STAT/SOCS-signaling pathway and colon and rectal cancer. Mol Carcinog. 52:155–166. 2013. View Article : Google Scholar : PubMed/NCBI