The Immunoregulatory of Hedgehog and NF-κB Signaling Pathway in Alveolar Epithelial TypeⅡ Cells Infected with Mycobacterium tuberculosis

doi:10.14088/j.cnki.issn0439-8114.2018.11.017

Abstract

Abstract: In order to investigate the roles of expression of Hedgehog and NF-κB signaling pathway signal molecules and inflammatory cytokines in the alveolar epithelial typeⅡ cells （AECⅡ） infected with Mycobacterium tuberculosis（Mtb）,the human AECⅡ cell line A549 was infected with Bacillus Calmette-Guérin（BCG,attenuated strain） and H37Rv （international standard virulent strain） respectively,and the signal molecules of Hedgehog and NF-κB signaling pathway and inflammatory cytokines in A549 cells of immune response to Mtb was detected by qPCR,and Western blot. The results showed that, the expression of Shh,Ptch and Gli1 in Hedgehog signaling pathway and the phosphorylation of NF-κB in NF-κB signaling pathway was increased in A549 cells when infected with H37Rv and BCG,and at the same time,the expression of IL-8 and TNF-α was also upregulated. And the protein expression of Shh,Ptch,Gli1 and NF-κB in A549 cells infected with H37Rv was higher than that infected with BCG. The Hedgehog and NF-κB signaling pathway could be activated, and the expression of inflammatory cytokines could be promoted in AECⅡ cells when infected with Mtb. The activation level of the both signaling pathway infected with Mtb virulent strain was higher than that of infected with BCG strain.

Key words: Mycobacterium tuberculosis, alveolar epithelial cells, Hedgehog, NF-kappaB, inflammatory cytokines

CLC Number:

S855.2

DU Jun, REN Qi-jie, WANG Yuan, WANG Juan, LI Yong. The Immunoregulatory of Hedgehog and NF-κB Signaling Pathway in Alveolar Epithelial TypeⅡ Cells Infected with Mycobacterium tuberculosis[J]. HUBEI AGRICULTURAL SCIENCES, 2018, 57(11): 70-74.

References

[1] SAKAMOTO K.The pathology of mycobacterium tuberculosis infection[J].Veterinary Pathology,2012,49(3):423-439.
[2] 陈焕春,郭爱珍.国内外牛结核病的防控历史与现状[A].中国畜牧兽医学会.中国畜牧兽医学会2009学术年会论文集(上册)[C].2009.3-6.
[3] MERAVIGLIA S,EL DAKER S,DIELI F,et al.Gammadelta T cells cross-link innate and adaptive immunity in Mycobacterium tuberculosis infection[J].Clinical & Developmental Immunology,2011:587315.
[4] KUGLER M C,JOYNER A L,LOOMIS C A,et al.Sonic hedgehog signaling in the lung. From development to disease[J].Am J Respir Cell Mol Biol,2015,52(1):1-13.
[5] RIMKUS T K,CARPENTER R L,QASEM S,et al.Targeting the sonic hedgehog signaling pathway:Review of smoothened and GLI inhibitors[J].Cancers(Basel),2016,8(2):E22.
[6] JIANG W G,YE L,RUGE F,et al.Expression of Sonic Hedgehog (SHH) in human lung cancer and the impact of YangZheng XiaoJi on SHH-mediated biological function of lung cancer cells and tumor growth[J].Anticancer Res,2015,35(3):1321-1331.
[7] BENVENUTO M,FANTINI M,MASUELLI L,et al.Inhibition of ErbB receptors,Hedgehog and NF-kappaB signaling by polyphenols in cancer[J].Front Biosci,2013,18:1290-1310.
[8] SCHUMACHER MA1,FENG R,AIHARA E,et al.Helicobacter pylori-induced Sonic Hedgehog expression is regulated by NFκB pathway activation:the use of a novel in vitro model to study epithelial response to infection[J].Helicobacter,2015,20(1):19-28.
[9] HOLLA S,STEPHEN-VICTOR E,PRAKHAR P,et al.Mycobacteria-responsive sonic hedgehog signaling mediates programmed death-ligand 1-and prostaglandin E2-induced regulatory T cell expansion[J].Science Report,2016,6:24193.
[10] MOREAU N,MAUBORGNE A,BOURGOIN S,et al.Early alterations of Hedgehog signaling pathway in vascular endothelial cells after peripheral nerve injury elicit blood-nerve barrier disruption,nerve inflammation,and neuropathic pain development[J].Pain,2016,157(4):827-839.
[11] SHERMAN A E,ZAVROS Y.Role of Sonic Hedgehog signaling during progression from inflammation to cancer in the stomach[J].World J Gastrointest Pathophysiol,2011,2(6):103-108.
[12] OMENETTI A,DIEHL A M.The adventures of sonic hedgehog in development and repair.Ⅱ.Sonic hedgehog and liver development,inflammation,and cancer[J].Am J Physiol Gastrointest Liver Physiol,2008,294(3):595-598.
[13] HOLLA S,GHORPADE D S,SINGH V,et al.Mycobacterium bovis BCG promotes tumor cell survival from tumor necrosis factor-alpha-induced apoptosis[J].Mol Cancer,2014,13:210.
[14] PANDAY A,INDA M E,BAGAM P,et al.Transcription Factor NF-κB:an update on intervention strategies[J].Arch Immunol Ther Exp (Warsz),2016,64(6):463-483.
[15] TAM A B,MERCADO E L,HOFFMANN A,et al.ER stress activates NF-kappaB by integrating functions of basal IKK activity, IRE1 and PERK[J].PLoS One,2012,7(10):e45078.
[16] MOTHES J,BUSSE D,KOFAHL B,et al.Sources of dynamic variability in NF-kappaB signal transduction:a mechanistic model[J].Bioessays,2015,37(4):452-462.
[17] GHOSH G,WANG V Y,HUANG D B,et al.NF-kappaB regulation:lessons from structures[J].Immunol Rev,2012,246(1): 36-58.
[18] 林丽艳,张慧云,何韶衡.IL-6及其受体与炎症性疾病关系的新进展[J].中国热带医学,2008,8(4):680-682.
[19] 向春艳,何小燕,李逐波,等.TNF-α在癌症中的作用研究进展[J].生命科学,2012,24(3):250-254.
[20] MEGYERI K,BUAZS K,MICZAK A,et al.The role of histamine in the intracellular survival of mycobacterium bovis BCG[J].Microbes Infect,2006,8(4):1035-1044.
[21] ROMERO-ADRIAN T B,LEAL-MONTIAL J,FRAN-NDEZ G,et al.Role of cytokines and other factors involved in the Mycobacterium tuberculosis infection[J].World Journal of Immunology,2015,5(1):16-50.
[22] 李瑶,吕德官,陈临溪.IL-8及其受体药物与疾病的研究进展[J].中国药理学通报,2014,30(3):310-314.
[23] 刘志东,许绍发,肖宁,等.IL-8和MMP-9在非小细胞肺癌患者组织及血清中表达水平的研究[J].中国肺癌杂志,2010, 13(8):795-802.
[24] 宋爱玲. TNF-α、IL-6、IL-8与溃疡性结肠炎严重程度相关研究[J].中国实用医药,2008,3(36):3-4.
[25] 刘东晓,程龙,王晓平,等.结核分枝杆菌(H37Rv和BCG)在感染AECⅡ细胞系A549中对TLRs信号通路和促炎因子表达的影响[J].农业生物技术学报,2016,24(2):252-260.
[26] MCDONOUGH K A,KRESS Y.Cytotoxicity for lung epithelial cells is a virulence-associated phenotype of Mycobacterium tuberculosis[J].Infect Immun,1995,63(12):4802-4811.