TY - JOUR
T1 - MicroRNA-98 and let-7 regulate expression of suppressor of cytokine signaling 4 in biliary epithelial cells in response to Cryptosporidium parvum infection
AU - Hu, Guoku
AU - Zhou, Rui
AU - Liu, Jun
AU - Gong, Ai Yu
AU - Chen, Xian Ming
N1 - Funding Information:
Received 21 October 2009; accepted 25 January 2010; electronically published 20 May 2010. Potential conflicts of interest: none reported. Financial support: National Institutes of Health (grant R01 AI071321 to X.-M.C.); Nebraska Tobacco Settlement Biomedical Research Program (grant LB692 to X.-M.C.). Reprints or correspondence: Dr Xian-Ming Chen, Dept of Medical Microbiology and Immunology, Creighton University Medical Center, Criss II, Room 529, 2500 California Plaza, Omaha, NE 68178 ([email protected]).
PY - 2010/7/1
Y1 - 2010/7/1
N2 - 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 miR98 caused reciprocal alterations in SOCS4 protein expression. Transfection of miR-98 precursor abolished C. parvwm-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.
AB - 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 miR98 caused reciprocal alterations in SOCS4 protein expression. Transfection of miR-98 precursor abolished C. parvwm-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.
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U2 - 10.1086/653212
DO - 10.1086/653212
M3 - Article
C2 - 20486857
AN - SCOPUS:77953688418
SN - 0022-1899
VL - 202
SP - 125
EP - 135
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 1
ER -