Role of Interleukin-27 in Pulmonary Infection with Respiratory Syncytial Virus_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

HeYanchao , ShiTianyun , ShiJindong , MeiZhoufang , QianLing , HuangQihui ,  JieZhijun

Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200240, China;

Corresponding author：

JieZhijun, Email: jiezjlxh@163.com

Keywords：

Interleukin-27; Respiratory syncytial virus; STAT1; pSTAT

DOI：

10.7507/1671-6205.2016084

Video：

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Objective To investigate expression level of interleukin-27 (IL-27)and its impact on virus replication in lung after infected with respiratory syncytial virus (RSV). Methods In vivo,7-week aged female C57 mice were infected with RSV and sacrificed on day 0,0.5,1,2,4,6,8 (n=5).The left lung was extracted for RNA,and then real-time PCR was used to detect the mRNA levels of IL-27p28,IL-27EBI3, RSV-M protein and interferon-β (IFN-β).The right lung was used for HE staining.In vitro, human lung epithelial cells (A549)were infected with RSV,and stimulated with different concentrations of recombinant human interleukin 27 (rhIL-27)in doses of 0,1ng/mL,10ng/mL,and 50ng/mL.After 24 hours,the mRNA expression of interferon induced transmembrane protein 3 (IFITM3),IFN-β,and RSV-M protein were determined by real-time PCR.IFITM3 and STAT1/pSTAT1 protein expression levels were detected by Western blot. Results The viral load in the lungs of mice peaked on 4 day post infection (DPI),then gradually decreased,and almost returned to normal on 8 DPI.IFN-β increased transiently 12 hours after infection,and then quickly returned to normal baseline.IL-27 p28/EBI3 levels peaked on 1 DPI,then gradually decreased to normal on 4 DPI.Stimulating RSV-infected A549 cells with rhIL-27 of 10ng/mL and 50ng/mL significantly inhibited viral replication,enhanced IFTIM3 mRNA expression,and induced STAT1 phosphorylation.However,rhIL-27 stimulation did not affect IFN-β mRNA expression. Conclusions The IL-27 mRNA expression increases after RSV infection.The inhibition of IL-27 on RSV replication might be related to up-regulation of STAT1 phosphorylation and IFITM3 protein expression.

Citation： HeYanchao, ShiTianyun, ShiJindong, MeiZhoufang, QianLing, HuangQihui, JieZhijun. Role of Interleukin-27 in Pulmonary Infection with Respiratory Syncytial Virus. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(4): 356-360. doi: 10.7507/1671-6205.2016084 Copy

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1. Borchers AT,Chang C,Gershwin ME,et al.Respiratory syncytial virus:a comprehensive review.Clin Rev Allergy Immunol,2013,45:331-379.
2. Chutiwitoonchai N,Hiyoshi M,Hiyoshi-Yoshidomi Y,et al.Characteristics of IFITM,the newly identified IFN-inducible anti-HIV-1 family proteins.Microbes Infect,2013,15:280-290.
3. Chesarino NM,McMichael TM,Yount JS.E3 ubiquitin ligase NEDD4 promotes influenza virus infection by decreasing levels of the antiviral protein IFITM3.PLoS Pathog,2015,11:e1005095.
4. Jia R,Pan Q,Ding S,et al.The N-terminal region of IFITM3 modulates its antiviral activity by regulating IFITM3 cellular localization.J Virol,2012,86:13697-13707.
5. Villarino AV,Huang E,Hunter CA.Understanding the pro- and anti-inflammatory properties of IL-27.J Immunol,2004,173:715-720.
6. Pflanz S,Hibbert L,Mattson J,et al.WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27.J Immunol,2004,172:2225-2231.
7. Fitzgerald DC,Fonseca-Kelly Z,Cullimore ML,et al.Independent and interdependent immunoregulatory effects of IL-27,IFN-β,and IL-10 in the suppression of human Th17 cells and murine experimental autoimmune encephalomyelitis.J Immunol,2013,190:3225-3234.
8. Liu L,Cao Z,Chen J,et al.Influenza A virus induces interleukin-27 through cyclooxygenase-2 and protein kinase A signaling.J Biol Chem,2012,287:11899-11910.
9. Iwasaki Y,Fujio K,Okamura T,et al.Interleukin-27 in T cell immunity.Int J Mol Sci,2015,16:2851-2863.
10. Wynick C,Petes C,Gee K.Interleukin-27 mediates inflammation during chronic disease.J Interferon Cytokine Res,2014,34:741-749.
11. Aparicio-Siegmund S,Garbers C.The biology of interleukin-27 reveals unique pro- and anti-inflammatory functions in immunity.Cytokine Growth Factor Rev,2015,26:579-586.
12. Zhang L,Liu J,Bai J,et al.Poly(I:C)inhibits porcine reproductive and respiratory syndrome virus replication in MARC-145 cells via activation of IFIT3.Antiviral Res,2013,99:197-206.
13. Kawai T,Akira S.Innate immune recognition of viral infection.Nat Immunol,2006,7:131-137.
14. Takaoka A,Yanai H.Interferon signalling network in innate defence.Cell Microbiol,2006,8:907-922.
15. Yao L,Dong H,Zhu H,et al.Identification of the IFITM3 gene as an inhibitor of hepatitis C viral translation in a stable STAT1 cell line.J Viral Hepat,2011,18:e523-e519.
16. Duan Y,Jia Y,Wang T,et al.Potent therapeutic target of inflammation,virus and tumor:focus on interleukin-27.Int Immunopharmacol,2015,26:139-146.

Chinese Journal of Respiratory and Critical Care Medicine

Role of Interleukin-27 in Pulmonary Infection with Respiratory Syncytial Virus

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