MicroRNA-98 and let-7 Regulate Expression of Suppressor of Cytokine Signaling 4 in Biliary Epithelial Cells in Response to Cryptosporidium parvum Infection

Expression of the cytokine-inducible Src homology 2 (CIS) protein and suppressors of cytokine signaling (SOCS) proteins represents an important element of host cell reactions in response to infection. We have demonstrated previously that Cryptosporidium parvum infection down-regulates microRNA-98 (m...

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Bibliographic Details
Published in:The Journal of infectious diseases 2010-07, Vol.202 (1), p.125-135
Main Authors: Hu, Guoku, Zhou, Rui, Liu, Jun, Gong, Ai-Yu, Chen, Xian-Ming
Format: Article
Language:English
Subjects:
Bile Ducts - cytology
Biological and medical sciences
Cell Line
Cryptosporidiosis
Cryptosporidium parvum - physiology
Cytokines
Epithelial cells
Epithelial Cells - metabolism
Epithelial Cells - parasitology
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation - physiology
Human protozoal diseases
Humans
Infections
Infectious diseases
Medical sciences
Messenger RNA
Microbiology
MicroRNA
MicroRNAs - genetics
MicroRNAs - metabolism
PARASITES
Parasitic diseases
Phosphorylation
Protein precursors
Protozoal diseases
RNA, Messenger - genetics
RNA, Messenger - metabolism
Stem cells
Suppressor of Cytokine Signaling Proteins - genetics
Suppressor of Cytokine Signaling Proteins - metabolism
Transfection
Untranslated regions
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Summary:Expression of the cytokine-inducible Src homology 2 (CIS) protein and suppressors of cytokine signaling (SOCS) proteins represents an important element of host cell reactions in response to infection. We have demonstrated previously that Cryptosporidium parvum infection down-regulates microRNA-98 (miR-98) and let-7 to induce CIS expression in biliary epithelial cells. We report here that down-regulation of miR-98 and let-7 also coordinates epithelial expression of SOCS4 after C. parvum infection. Targeting of the SOCS4 3′ untranslated region by miR-98 or let-7 resulted in translational repression. Functional manipulation of miR-98 caused reciprocal alterations in SOCS4 protein expression. Transfection of miR-98 precursor abolished C. parvum-stimulated SOCS4 up-regulation. Moreover, expression of SOCS4 in epithelial cells showed an inhibitory effect on phosphorylation of signal transducers and activators of transcription proteins induced by C. parvum. These data suggest that miRNAs play an important role in the coordinated regulation of CIS and SOCS expression in epithelial cells in response to C. parvum infection.
ISSN:0022-1899
1537-6613
DOI:10.1086/653212