title: MicroRNA-221 controls expression of intercellular adhesion molecule-1 in epithelial cells in response to Cryptosporidium parvum infection.
abstract: Cryptosporidium parvum is a protozoan parasite that infects gastrointestinal epithelial cells and causes diarrhoeal disease in humans and animals globally. Pathological changes following C. parvum infection include crypt hyperplasia and a modest inflammatory reaction with increased infiltration of lymphocytes into intestinal mucosa. Expression of adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), on infected epithelial cell surfaces may facilitate adhesion and recognition of lymphocytes at infection sites. MicroRNAs (miRNAs) are small RNA molecules of 23 nucleotides that negatively regulate protein-coding gene expression via translational suppression or mRNA degradation. We recently reported that microRNA-221 (miR-221) regulates ICAM-1 translation through targeting the ICAM-1 3'-untranslated region (UTR). In this study, we tested the role of miR-221 in regulating ICAM-1 expression in epithelial cells in response to C. parvum infection using an in vitro model of human biliary cryptosporidiosis. Up-regulation of ICAM-1 at both message and protein levels was detected in epithelial cells following C. parvum infection. Inhibition of ICAM-1 transcription with actinomycin D could only partially block C. parvum-induced ICAM-1 expression at the protein level. Cryptosporidium parvum infection decreased miR-221 expression in infected epithelial cells. When cells were transfected with a luciferase reporter construct covering the miR-221 binding site in the ICAM-1 3'-UTR and then exposed to C. parvum, an enhanced luciferase activity was detected. Transfection of miR-221 precursor abolished C. parvum-stimulated ICAM-1 protein expression. In addition, expression of ICAM-1 on infected epithelial cells facilitated epithelial adherence of co-cultured Jurkat cells. These results indicate that miR-221-mediated translational suppression controls ICAM-1 expression in epithelial cells in response to C. parvum infection.
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE 68178, USA.
authors.forename: Ai-Yu
authors.initials: AY
authors.lastname: Gong
authors.forename: Guoku
authors.initials: G
authors.lastname: Hu
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Yaoyu
authors.initials: Y
authors.lastname: Feng
authors.forename: Garrett A
authors.initials: GA
authors.lastname: Soukup
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Chen
mesh_terms: D000818:Animals; D001659:Biliary Tract / Q000166:cytology / Q000469:parasitology; D003457:Cryptosporidiosis / Q000469:parasitology; D016785:Cryptosporidium parvum / Q000472:pathogenicity*; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells / Q000469:parasitology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D018799:Intercellular Adhesion Molecule-1