Induction of microRNA-155 during Helicobacter pylori Infection and Its Negative Regulatory Role in the Inflammatory Response

• Published in: The Journal of infectious diseases 2009-09, Vol.200 (6), p.916-925
• Main Authors: Xiao, Bin, Liu, Zhen, Li, Bo-Sheng, Tang, Bin, Li, Wei, Guo, Gang, Shi, Yun, Wang, Fengjun, Wu, Yuan, Tong, Wen-De, Guo, Hong, Mao, Xu-Hu, Zou, Quan-Ming
• Format: Article
• Language: English
• Subjects: Adult; B lymphocytes; BACTERIA; Bacteriology; Biological and medical sciences; Chemokine CXCL1 - metabolism; Epithelial cells; Fas-Associated Death Domain Protein - metabolism; Female; Fundamental and applied biological sciences. Psychology; Gastric Mucosa - metabolism; Gene Expression Profiling; Gene Expression Regulation; Helicobacter Infections - metabolism; Helicobacter Infections - microbiology; Helicobacter pylori; Humans; I-kappa B Kinase - metabolism; Infections; Infectious diseases; Inflammation; Inflammation - metabolism; Interleukin-8 - metabolism; Male; Medical sciences; Messenger RNA; Microbiology; MicroRNA; MicroRNAs - metabolism; Middle Aged; Miscellaneous; NF-kappa B - metabolism; Oligonucleotide Array Sequence Analysis; RNA; Smad2 Protein - metabolism; Transfection; Up regulation
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/605443

BackgroundMicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression at posttranscriptional level. H. pylori is a major human pathogenic bacterium in gastric mucosa. To date, the role of miRNAs in response to H. pylori infection has not been explored MethodsThe expression profile of cellular miRNAs during H. pylori infection was analyzed by using microarray and quantitative reverse-transcriptase polymerase chain reaction. The potential target of miR-155 was identified by luciferase assay and Western blot. Promoter analysis and inhibitor experiment were used to investigate the pathway involved in the induction of miR-155. Examination of miR-155 function was performed by overexpression and inhibition of miR-155 ResultsH. pylori was able to increase the miR-155 expression in gastric epithelial cell lines and gastric mucosal tissues, and nuclear factor–κB (NF-κB) and activator protein–1 (AP-1) pathway were required for the induction of miR-155. miR-155 may down-regulate IκB kinase ɛ, Sma- and Mad-related protein 2 (SMAD2), and Fas-associated death domain protein. Furthermore, the overexpression of miR-155 negatively regulated the release of interleukin-8 and growth-related oncogene–α ConclusionsThis study provides the first description of increased expression of miR-155 in H. pylori infection, and miR-155 may function as novel negative regulator that help to fine-tune the inflammation response of H. pylori infection