title: Selective upregulation of microRNA expression in peripheral blood leukocytes in IL-10-/- mice precedes expression in the colon.
abstract: IL-10(-/-) mice, an animal model of Th1-mediated inflammatory bowel disease, were screened for the expression of 600 microRNAs (miRNAs) using colonic tissues and PBLs from animals having either mild inflammation or severe intestinal inflammation. The development of colonic inflammation in IL-10(-/-) mice was accompanied by upregulation in the expression of 10 miRNAs (miR-19a, miR-21, miR-31, miR-101, miR-223, miR-326, miR-142-3p, miR-142-5p, miR-146a, and miR-155). Notably, the expression of all of these miRNAs plus miR-375 was elevated in PBLs of IL-10(-/-) mice at a time when colonic inflammation was minimal, suggesting that changes in specific miRNAs in circulating leukocytes may be harbingers of ensuing colonic pathology. In vitro exposure of colonic intraepithelial lymphocytes to IL-10 resulted in downregulation of miR-19a, miR-21, miR-31, miR-101, miR-223, and miR-155. Interestingly, unlike IL-10(-/-) mice, changes in miRNAs in PBL of dextran sulfate sodium-treated mice were minimal but selectively elevated in the colon after pathology was severe. We further show that miR-223 is a negative regulator of the Roquin ubiquitin ligase, Roquin curtails IL-17A synthesis, and the 3' untranslated region of Roquin is a target for miR-223, thus defining a molecular pathway by which IL-10 modulates IL-17-mediated inflammation. To identify additional miRNAs that may be involved in the regulation of Roquin, transcriptome analysis was done using cDNAs from HeLa cells transfected with 90 miRNA mimics. Twenty-six miRNAs were identified as potential negative regulators of Roquin, thus demonstrating functional complexity in gene expression regulation by miRNAs.
authors: Department of Diagnostic Sciences, Dental Branch, The University of Texas Health Science Center at Houston, TX 77030, USA.
authors: Jeremy S
authors: JS
authors: Schaefer
authors: Dina
authors: D
authors: Montufar-Solis
authors: Nadarajah
authors: N
authors: Vigneswaran
authors: John R
authors: JR
authors: Klein
mesh_terms: D000818:Animals; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics* / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000172:deficiency / Q000276:immunology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D035683:MicroRNAs / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D016753:Interleukin-10