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MicroRNA regulation of innate immune responses in epithelial cells

Cellular & Molecular Immunology volume 8, pages 371–379 (2011)Cite this article

Abstract

Mucosal surface epithelial cells are equipped with several defense mechanisms that guard against pathogens. Recent studies indicate that microRNAs (miRNAs) mediate post-transcriptional gene suppression and may be a critical component of the complex regulatory networks in epithelial immune responses. Transcription of miRNA genes in epithelial cells can be elaborately controlled through pathogen recognition receptors, such as Toll-like receptors (TLRs), and associated nuclear factor kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, and ultimately nuclear transcription factor associated-transactivation and transrepression. Activation of these intracellular signaling pathways may also modulate the process of miRNA maturation. Functionally, miRNAs may modulate epithelial immune responses at every step of the innate immune network, including production and release of cytokines/chemokines, expression of adhesion and costimulatory molecules, shuttling of miRNAs through release of exosomes and feedback regulation of immune homeostasis. Therefore, miRNAs act as critical regulators to the fine-tuning of epithelial immune responses.

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References

  1. Viswanathan VK, Hecht G . Innate immunity and the gut. Curr Opin Gastroenterol 2000; 16: 546–551.

    Article  CAS  PubMed  Google Scholar 

  2. Akira S, Takeda K . Toll-like receptor signalling. Nat Rev Immunol 2004; 4: 499–511.

    Article  CAS  PubMed  Google Scholar 

  3. Kobayashi KS, Flavell RA . Shielding the double-edged sword: negative regulation of the innate immune system. J Leukoc Biol 2004; 75: 428–433.

    Article  CAS  PubMed  Google Scholar 

  4. Chen XM, O'Hara SP, LaRusso NF . The immunobiology of cholangiocytes. Immunol Cell Biol 2008; 86: 497–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bartel DP . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281–297.

    Article  CAS  PubMed  Google Scholar 

  6. Ambros V . The functions of animal microRNAs. Nature 2004; 431: 350–355.

    Article  CAS  PubMed  Google Scholar 

  7. Krol J, Loedige I, Filipowicz W . The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 2010; 11: 597–610.

    Article  CAS  PubMed  Google Scholar 

  8. Liu J, Drescher KM, Chen XM . MicroRNAs and epithelial Immunity. Int Rev Immunol 2009; 28: 139–154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J 2004; 23: 4051–4060.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Winter J, Jung S, Keller S, Gregory RI, Diederichs S . Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 2009; 11: 228–234.

    Article  CAS  PubMed  Google Scholar 

  11. Kozomara A, Griffiths-Jones S . miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 2011; 39: D152–D157.

    Article  CAS  PubMed  Google Scholar 

  12. Davis BN, Hata A . Regulation of MicroRNA biogenesis: a miRiad of mechanisms. Cell Commun Signal 2009; 7: 18.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Saini HK, Griffiths-Jones S, Enright AJ . Genomic analysis of human microRNA transcripts. Proc Natl Acad Sci USA 2007; 104: 17719–17724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A . Identification of mammalian microRNA host genes and transcription units. Genome Res 2004; 14: 1902–1910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Li X, Liu J, Zhou R, Huang S, Huang S, Chen XM . Gene silencing of MIR22 in acute lymphoblastic leukaemia involves histone modifications independent of promoter DNA methylation. Br J Haematol 2010; 148: 69–79.

    Article  CAS  PubMed  Google Scholar 

  16. Corcoran DL, Pandit KV, Gordon B, Bhattacharjee A, Kaminski N, Benos PV . Features of mammalian microRNA promoters emerge from polymerase II chromtatin immunoprecipitation data. PLoS One 2009; 4: e5279.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Altuvia Y, Landgraf P, Lithwick G, Elefant N, Pfeffer S, Aravin A et al. Clustering and conservation patterns of human microRNAs. Nucleic Acids Res 2005; 33: 2697–2706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004; 101: 2999–3004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yu J, Wang F, Yang GH, Wang FL, Ma YN, Du ZW et al. Human microRNA clusters: genomic organization and expression profile in leukemia cell lines. Biochem Biophys Res Commun 2006; 349: 59–68.

    Article  CAS  PubMed  Google Scholar 

  20. Hayden MS, Ghosh S . Shared principles in NF-κB signaling. Cell 2008; 132: 344–362.

    Article  CAS  PubMed  Google Scholar 

  21. Han J, Ulevitch RJ . Limiting inflammatory responses during activation of innate immunity. Nat Immunol 2005; 6: 1198–1205.

    Article  CAS  PubMed  Google Scholar 

  22. Harada K, Ohira S, Isse K, Ozaki S, Zen Y, Sato Y et al. Lipopolysaccharide activates nuclear factor-kappaB through Toll-like receptors and related molecules in cultured biliary epithelial cells. Lab Invest 2003; 83: 1657–1667.

    Article  CAS  PubMed  Google Scholar 

  23. Poppelmann B, Klimmek K, Strozyk E, Voss R, Schwarz T, Kulms D . NFkappaB-dependent down-regulation of tumor necrosis factor receptor-associated proteins contributes to interleukin-1-mediated enhancement of ultraviolet B-induced apoptosis. J Biol Chem 2005; 280: 15635–15643.

    Article  PubMed  CAS  Google Scholar 

  24. Kim S, Domon-Dell C, Kang J, Chung DH, Freund JN, Evers BM . Down-regulation of the tumor suppressor PTEN by the tumor necrosis factor-alpha/nuclear factor-kappaB (NF-kappaB)-inducing kinase/NF-kappaB pathway is linked to a default IkappaB-alpha autoregulatory loop. J Biol Chem 2004; 279: 4285–4291.

    Article  CAS  PubMed  Google Scholar 

  25. Taganov KD, Boldin MP, Chang KJ, Baltimore D . NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 2006; 103: 12481–12486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jennewein C, von Knethen A, Schmid T, Brüne B . MicroRNA-27b contributes to lipopolysaccharide-mediated peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA destabilization. J Biol Chem 2010; 285: 11846–11853.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bazzoni F, Rossato M, Fabbri M, Gaudiosi D, Mirolo M, Mori L et al. Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals. Proc Natl Acad Sci USA 2009; 106: 5282–5287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. O'Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D . MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA 2007; 104: 1604–1609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gatto G, Rossi A, Rossi D, Kroening S, Bonatti S, Mallardo M . Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kappaB pathway. Nucleic Acids Res 2008; 36: 6608–6619.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Perry MM, Moschos SA, Williams AE, Shepherd NJ, Larner-Svensson HM, Lindsay MA . Rapid changes in microRNA-146a expression negatively regulate the IL-1beta-induced inflammatory response in human lung alveolar epithelial cells. J Immunol 2008; 180: 5689–5698.

    Article  CAS  PubMed  Google Scholar 

  31. Cameron JE, Yin Q, Fewell C, Lacey M, McBride J, Wang X et al. Epstein–Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways. J Virol 2008; 82: 1946–1958.

    Article  CAS  PubMed  Google Scholar 

  32. Shin VY, Jin H, Ng EK, Cheng AS, Chong WW, Wong CY et al. NF-κB targets miR-16 and miR-21 in gastric cancer: involvement of prostaglandin E receptors. Carcinogenesis 2011; 32: 240–245.

    Article  CAS  PubMed  Google Scholar 

  33. Lu Z, Li Y, Takwi A, Li B, Zhang J, Conklin DJ et al. miR-301a as an NF-κB activator in pancreatic cancer cells. EMBO J 2011; 30: 57–67.

    Article  CAS  PubMed  Google Scholar 

  34. Zhou R, Hu G, Gong AY, Chen XM . Binding of NF-kappaB p65 subunit to the promoter elements is involved in LPS-induced transactivation of miRNA genes in human biliary epithelial cells. Nucleic Acids Res 2010; 38: 3222–3232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhou R, Hu G, Liu J, Gong AY, Drescher KM, Chen XM . NF-kappaB p65-dependent transactivation of miRNA genes following Cryptosporidium parvum infection stimulates epithelial cell immune responses. PLoS Pathog 2009; 5: e1000681.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. O'Hara SP, Splinter PL, Gajdos GB, Trussoni CE, Fernandez-Zapico ME, Chen XM et al. NFkappaB p50-CCAAT/enhancer-binding protein beta (C/EBPbeta)-mediated transcriptional repression of microRNA let-7i following microbial infection. J Biol Chem 2010; 285: 216–225.

    Article  CAS  PubMed  Google Scholar 

  37. Liu S, Wu LC, Pang J, Santhanam R, Schwind S, Wu YZ et al. Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia. Cancer Cell 2010; 17: 333–347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wang H, Garzon R, Sun H, Ladner KJ, Singh R, Dahlman J et al. NF-κB-YY1-miR-29 Regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell 2008; 14: 369–381.

    Article  CAS  PubMed  Google Scholar 

  39. Whitmarsh AJ, Davis RJ . Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med 1996; 74: 589–607.

    Article  CAS  PubMed  Google Scholar 

  40. Fujita S, Ito T, Mizutani T, Minoguchi S, Yamamichi N, Sakurai K et al. miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism. J Mol Biol 2008; 378: 492–504.

    Article  CAS  PubMed  Google Scholar 

  41. Misawa A, Katayama R, Koike S, Tomida A, Watanabe T, Fujita N . AP-1-Dependent miR-21 expression contributes to chemoresistance in cancer stem cell-like SP cells. Oncol Res 2010; 19: 23–33.

    Article  CAS  PubMed  Google Scholar 

  42. Shao M, Rossi S, Chelladurai B, Shimizu M, Ntukogu O, Ivan M et al. PDGF induced microRNA alterations in cancer cells. Nucleic Acids Res 2011; 39: 4035–4047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Yin Q, Wang X, McBride J, Fewell C, Flemington E . B-cell receptor activation induces BIC/miR-155 expression through a conserved AP-1 element. J Biol Chem 2008; 283: 2654–2662.

    Article  CAS  PubMed  Google Scholar 

  44. Oneyama C, Ikeda J, Okuzaki D, Suzuki K, Kanou T, Shintani Y et al. MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways. Oncogene 2011; in press.

  45. Ding XC, Weiler J, Grosshans H . Regulating the regulators: mechanisms controlling the maturation of microRNAs. Trends Biotechnol 2009; 27: 27–36.

    Article  CAS  PubMed  Google Scholar 

  46. Fukuda T, Yamagata K, Fujiyama S, Matsumoto T, Koshida I, Yoshimura K et al. DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs. Nat Cell Biol 2007; 9: 604–611.

    Article  CAS  PubMed  Google Scholar 

  47. Davis BN, Hilyard AC, Lagna G, Hata A . SMAD proteins control DROSHA-mediated microRNA maturation. Nature 2008; 454: 56–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Guil S, Caceres JF . The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a. Nat Struct Mol Biol 2007; 14: 591–596.

    Article  CAS  PubMed  Google Scholar 

  49. Michlewski G, Guil S, Semple CA, Caceres JF . Posttranscriptional regulation of miRNAs harboring conserved terminal loops. Mol Cell 2008; 32: 383–393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Shimada N, Rios I, Moran H, Sayers B, Hubbard K . p38 MAP kinase dependent regulation of the expression level and subcellular distribution of heterogeneous nuclear ribonucleoprotein A1 and its involvement in cellular senescence in normal human fibroblasts. RNA Biol 2009; 6: 293–304.

    Article  CAS  PubMed  Google Scholar 

  51. Trabucchi M, Briata P, Garcia-Mayoral M, Haase AD, Filipowicz W, Ramos A et al. The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature 2009; 459: 1010–1014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ruggiero T, Trabucchi M, de Santa F, Zupo S, Harfe BD, McManus MT et al. LPS induces KH-type splicing regulatory protein-dependent processing of microRNA-155 precursors in macrophages. FASEB J 2009; 23: 2898–2908.

    Article  CAS  PubMed  Google Scholar 

  53. Dean JL, Sully G, Clark AR, Saklatvala J . The involvement of AU-rich element-binding proteins in p38 mitogen-activated protein kinase pathway-mediated mRNA stabilisation. Cell Signal 2004; 16: 1113–1121.

    Article  CAS  PubMed  Google Scholar 

  54. Melo SA, Ropero S, Moutinho C, Aaltonen LA, Yamamoto H, Calin GA et al. A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nat Genet 2009; 41: 365–370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Paroo Z, Ye X, Chen S, Liu Q . Phosphorylation of the human microRNA-generating complex mediates MAPK/Erk signaling. Cell 2009; 139: 112–122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Melo S, Villanueva A, Moutinho C, Davalos V, Spizzo R, Ivan C et al. Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing. Proc Natl Acad Sci USA 2011; 108: 4394–4399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Asirvatham AJ, Gregorie CJ, Hu Z, Magner WJ, Tomasi TB . MicroRNA targets in immune genes and the Dicer/Argonaute and ARE machinery components. Mol Immunol 2008; 45: 1995–2006.

    Article  CAS  PubMed  Google Scholar 

  58. Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B et al. Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNFalpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 2007; 179: 5082–5089.

    Article  CAS  PubMed  Google Scholar 

  59. Jing Q, Huang S, Guth S, Zarubin T, Motoyama A, Chen J et al. Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell 2005; 120: 623–634.

    Article  CAS  PubMed  Google Scholar 

  60. Witwer KW, Sisk JM, Gama L, Clements JE . MicroRNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune response. J Immunol 2010; 184: 2369–2376.

    Article  CAS  PubMed  Google Scholar 

  61. Ueda R, Kohanbash G, Sasaki K, Fujita M, Zhu X, Kastenhuber ER et al. Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1. Proc Natl Acad Sci USA 2009; 106: 10746–10751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kawahigashi Y, Mishima T, Mizuguchi Y, Arima Y, Yokomuro S, Kanda T et al. MicroRNA profiling of human intrahepatic cholangiocarcinoma cell lines reveals biliary epithelial cell-specific microRNAs. J Nippon Med Sch 2009; 76: 188–197.

    Article  CAS  PubMed  Google Scholar 

  63. Hu G, Gong AY, Liu J, Zhou R, Deng C, Chen XM . miR-221 suppresses ICAM-1 translation and regulates interferon-gamma-induced ICAM-1 expression in human cholangiocytes. Am J Physiol 2010; 298: 542–550.

    Article  CAS  Google Scholar 

  64. Suárez Y, Wang C, Manes TD, Pober JS . Cutting edge: TNF-induced microRNAs regulate TNF-induced expression of E-selectin and intercellular adhesion molecule-1 on human endothelial cells: feedback control of inflammation. J Immunol 2010; 184: 21–25.

    Article  PubMed  CAS  Google Scholar 

  65. Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ . MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci USA 2008; 105: 1516–1521.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Gong AY, Zhou R, Hu G, Li X, Splinter PL, O'Hara SP et al. MicroRNA-513 regulates B7-H1 translation and is involved in interferon-gamma-induced B7-H1 expression in cholangiocytes. J Immunol 2009; 182: 1325–1333.

    Article  CAS  PubMed  Google Scholar 

  67. Gong AY, Zhou R, Hu G, Liu J, Sosnowska D, Drescher KM et al. Cryptosporidium parvum induces B7-H1 expression in cholangiocytes by down-regulating microRNA-513. J Infect Dis 2010; 201: 160–169.

    Article  CAS  PubMed  Google Scholar 

  68. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO . Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9: 654–659.

    Article  CAS  PubMed  Google Scholar 

  69. Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 2008; 3: e3694.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Kesimer M, Scull M, Brighton B, DeMaria G, Burns K, O'Neal W et al. Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense. FASEB J 2009; 23: 1858–1868.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ohshima K, Inoue K, Fujiwara A, Hatakeyama K, Kanto K, Watanabe Y et al. Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS One 2010; 5: e13247.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Otsuka M, Jing Q, Georgel P, New L, Chen J, Mols J et al. Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression. Immunity 2007; 27: 123–134.

    Article  CAS  PubMed  Google Scholar 

  73. Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV et al. Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 2007; 449: 919–922.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Ahluwalia JK, Khan SZ, Soni K, Rawat P, Gupta A, Hariharan M et al. Human cellular microRNA hsa-miR-29a interferes with viral nef protein expression and HIV-1 replication. Retrovirology 2008; 5: 117.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Huang J, Wang F, Argyris E, Chen K, Liang Z, Tian H et al. Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nat Med 2007; 13: 1241–1247.

    Article  CAS  PubMed  Google Scholar 

  76. Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C et al. A cellular microRNA mediates antiviral defense in human cells. Science 2005; 308: 557–560.

    Article  CAS  PubMed  Google Scholar 

  77. Wang P, Hou J, Lin L, Wang C, Liu X, Li D et al. Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1. Immunology 2010; 185: 6226–6233.

    Article  CAS  Google Scholar 

  78. Chen XM, Splinter PL, O'Hara SP, LaRusso NF . A cellular micro-RNA, let-7i, regulates Toll-like receptor 4 expression and contributes to cholangiocyte immune responses against Cryptosporidium parvum infection. J Biol Chem 2007; 282: 28929–28938.

    Article  CAS  PubMed  Google Scholar 

  79. Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P . Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 2005; 309: 1577–1581.

    Article  CAS  PubMed  Google Scholar 

  80. Linnstaedt SD, Gottwein E, Skalsky RL, Luftig MA, Cullen BR . Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein–Barr virus. J Virol 2010; 84: 11670–11678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Lagos D, Pollara G, Henderson S, Gratrix F, Fabani M, Milne RS et al. miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator. Nat Cell Biol 2010; 12: 513–519.

    Article  CAS  PubMed  Google Scholar 

  82. Triboulet R, Mari B, Lin YL, Chable-Bessia C, Bennasser Y, Lebrigand K et al. Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science 2007; 315: 1579–1582.

    Article  CAS  PubMed  Google Scholar 

  83. Ceppi M, Pereira PM, Dunand-Sauthier I, Barras E, Reith W, Santos MA et al. MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc Natl Acad Sci USA 2009; 106: 2735–2740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Tang B, Xiao B, Liu Z, Li N, Zhu ED, Li BS et al. Identification of MyD88 as a novel target of miR-155, involved in negative regulation of Helicobacter pylori-induced inflammation. FEBS Lett 2010; 584: 1481–1486.

    Article  CAS  PubMed  Google Scholar 

  85. Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O'Leary JJ, Ruan Q et al. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol 2010; 11: 141–147.

    Article  CAS  PubMed  Google Scholar 

  86. Hu G, Zhou R, Liu Jiu, Gong AY, Eischeid AN, Dittman JW et al. MicroRNA-98 and let-7 confer cholangiocyte expression of cytokine-inducible Src homology 2-containing protein in response to microbial challenge. J Immunol 2009; 183: 1617–1624.

    Article  CAS  PubMed  Google Scholar 

  87. Zhu QY, Liu Q, Chen JX, Lan K, Ge BX . MicroRNA-101 targets MAPK phosphatase-1 to regulate the activation of MAPKs in macrophages. J Immunol 2010; 185: 7435–7442.

    Article  CAS  PubMed  Google Scholar 

  88. Ørom UA, Lund AH . Experimental identification of microRNA targets. Gene 2010; 451: 1–5.

    Article  PubMed  CAS  Google Scholar 

  89. Leung AK, Young AG, Bhutkar A, Zheng GX, Bosson AD, Nielsen CB et al. Genome-wide identification of Ago2 binding sites from mouse embryonic stem cells with and without mature microRNAs. Nat Struct Mol Biol 2011; 18: 237–244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kota J, Chivukula RR, O'Donnell KA, Wentzel EA, Montgomery CL, Hwang HW et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 2009; 137: 1005–1017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Sharma AD, Narain N, Händel EM, Iken M, Singhal N, Cathomen T et al. MicroRNA-221 regulates FAS-induced fulminant liver failure. Hepatology 2011; 53: 1651–1661.

    Article  CAS  PubMed  Google Scholar 

  92. Androulidaki A, Iliopoulos D, Arranz A, Doxaki C, Schworer S, Zacharioudaki V et al. The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs. Immunity 2009; 31: 220–231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Alsaleh G, Suffert G, Semaan N, Juncker T, Frenzel L, Gottenberg JE et al. Bruton's tyrosine kinase is involved in miR-346-related regulation of IL-18 release by lipopolysaccharide-activated rheumatoid fibroblast-like synoviocytes. J Immunol 2009; 82: 5088–5097.

    Article  CAS  Google Scholar 

  94. El Gazzar M, McCall CE . MicroRNAs distinguish translational from transcriptional silencing during endotoxin tolerance. J Biol Chem 2010; 285: 20940–20951.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Huang TH, Wu F, Loeb GB, Hsu R, Heidersbach A, Brincat A et al. Up-regulation of miR-21 by HER2/neu signaling promotes cell invasion. J Biol Chem 2009; 284: 18515–18524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Martinez-Nunez RT, Louafi F, Sanchez-Elsner T . The interleukin 13 (IL-13) pathway in human macrophages is modulated by microRNA-155 via direct targeting of interleukin 13 receptor alpha1 (IL13Ralpha1). J Biol Chem 2011; 286: 1786–1794.

    Article  CAS  PubMed  Google Scholar 

  97. Yin Q, McBride J, Fewell C, Lacey M, Wang X, Lin Z et al. MicroRNA-155 is an Epstein–Barr virus-induced gene that modulates Epstein–Barr virus-regulated gene expression pathways. J Virol 2008; 82: 5295–5306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Worm J, Stenvang J, Petri A, Frederiksen KS, Obad S, Elmén J et al. Silencing of microRNA-155 in mice during acute inflammatory response leads to derepression of C/EBPβ and down-regulation of G-CSF. Nucleic Acids Res 2009; 37: 5784–5792.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Schembri F, Sridhar S, Perdomo C, Gustafson AM, Zhang X, Ergun A et al. MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium. Proc Natl Acad Sci USA 2009; 106: 2319–2324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Sonkoly E, Wei T, Janson PC, Sääf A, Lundeberg L, Tengvall-Linder M et al. MicroRNAs: novel regulators involved in the pathogenesis of Psoriasis? PLoS One 2007; 2: e610

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Wu F, Zikusoka M, Trindade A, Dassopoulos T, Harris ML, Bayless TM et al. MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2 alpha. Gastroenterology 2008; 135: 1624–1635.

    Article  CAS  PubMed  Google Scholar 

  102. Hu G, Zhou R, Liu J, Gong AY, Chen XM . MicroRNA-98 and let-7 regulate expression of suppressor of cytokine signaling 4 in biliary epithelial cells in response to Cryptosporidium parvum infection. J Infect Dis 2010; 202: 125–135.

    Article  CAS  PubMed  Google Scholar 

  103. Oglesby IK, Bray IM, Chotirmall SH, Stallings RL, O'Neill SJ, McElvaney NG et al. miR-126 is downregulated in cystic fibrosis airway epithelial cells and regulates TOM1 expression. J Immunol 2010; 184: 1702–1709.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by National Institute of health (NIH) grant AI071321, AI095532 and by the Nebraska Tobacco Settlement Biomedical Research Program (LB692 and LB595) (to XM Chen) and NIH grant AI089713 (to SP O'Hara).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, USA

    Rui Zhou & Xian-Ming Chen

  2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA

    Steven P O'Hara

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  2. Steven P O'Hara
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  3. Xian-Ming Chen
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Zhou, R., O'Hara, S. & Chen, XM. MicroRNA regulation of innate immune responses in epithelial cells. Cell Mol Immunol 8, 371–379 (2011). https://doi.org/10.1038/cmi.2011.19

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