MicroRNA-221 controls expression of intercellular adhesion molecule-1 in epithelial cells in response to Cryptosporidium parvum infection

Ai Yu Gong, Guoku Hu, Rui Zhou, Jun Liu, Yaoyu Feng, Garrett A. Soukup, Xian Ming Chen

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)397-403
Number of pages7
JournalInternational Journal for Parasitology
Volume41
Issue number3
DOIs
StatePublished - Feb 7 2011

Fingerprint

Cryptosporidium parvum
Intercellular Adhesion Molecule-1
MicroRNAs
Epithelial Cells
Infection
3' Untranslated Regions
Luciferases
Proteins
Lymphocytes
Cryptosporidiosis
Jurkat Cells
RNA Stability
Dactinomycin
Intestinal Mucosa
Hyperplasia
Transfection
Cultured Cells
Parasites
Up-Regulation
Nucleotides

Keywords

  • Adhesion molecules
  • Cryptosporidium parvum
  • Epithelial cells
  • ICAM-1
  • Inflammation
  • Lymphocytes
  • MicroRNAs

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

MicroRNA-221 controls expression of intercellular adhesion molecule-1 in epithelial cells in response to Cryptosporidium parvum infection. / Gong, Ai Yu; Hu, Guoku; Zhou, Rui; Liu, Jun; Feng, Yaoyu; Soukup, Garrett A.; Chen, Xian Ming.

In: International Journal for Parasitology, Vol. 41, No. 3, 07.02.2011, p. 397-403.

Research output: Contribution to journalArticle

Gong, Ai Yu ; Hu, Guoku ; Zhou, Rui ; Liu, Jun ; Feng, Yaoyu ; Soukup, Garrett A. ; Chen, Xian Ming. / MicroRNA-221 controls expression of intercellular adhesion molecule-1 in epithelial cells in response to Cryptosporidium parvum infection. In: International Journal for Parasitology. 2011 ; Vol. 41, No. 3. pp. 397-403.
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