Cryptosporidium parvum induces SIRT1 expression in host epithelial cells through downregulating let-7i

Hongguan Xie, Ningfei Lei, Ai Yu Gong, Xian Ming Chen, Guoku Hu

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Epithelial cells along human gastrointestinal mucosal surface express pathogen-recognizing receptors and actively participate in the regulation of inflammatory reactions in response to microbial infection. The NAD-dependent deacetylase sirtuin-1 (SIRT1), one member of the sirtuin family of proteins and an NAD-dependent deacetylase has been implicated in the regulation of multiple cellular processes, including inflammation, longevity, and metabolism. In this study, we demonstrated that infection of cultured human biliary epithelial cells (H69 cholangiocytes) with a parasitic protozoan, Cryptosporidium parvum, induced SIRT1 expression at the protein level without a change in SIRT1 mRNA content. Using real-time PCR and Northern blot analyses, we found that C. parvum infection decreased the expression of let-7i in infected H69 cells. Down-regulation of let-7i caused relief of miRNA-mediated translational suppression of SIRT1 and consequently, resulted in an increased SIRT1 protein level in infected H69 cell cultures. Moreover, gain- and loss-of-function studies revealed that let-7i could modulate NF-κB activation through modification of SIRT1 protein expression. Thus, our data suggest that let-7i regulates SIRT1 expression in human biliary epithelial cells in response to microbial challenge, suggesting a new role of let-7i in the regulation of NF-κB-mediated epithelial innate immune response.

Original languageEnglish (US)
Pages (from-to)760-765
Number of pages6
JournalHuman Immunology
Volume75
Issue number8
DOIs
StatePublished - Jan 1 2014

Fingerprint

Sirtuin 1
Cryptosporidium parvum
Down-Regulation
Epithelial Cells
NAD
Proteins
Infection
MicroRNAs
Innate Immunity
Northern Blotting
Real-Time Polymerase Chain Reaction
Cell Culture Techniques
Inflammation
Messenger RNA

Keywords

  • C. parvum
  • Epithelium
  • Let-7
  • NF-κB
  • SIRT1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Cryptosporidium parvum induces SIRT1 expression in host epithelial cells through downregulating let-7i. / Xie, Hongguan; Lei, Ningfei; Gong, Ai Yu; Chen, Xian Ming; Hu, Guoku.

In: Human Immunology, Vol. 75, No. 8, 01.01.2014, p. 760-765.

Research output: Contribution to journalArticle

Xie, Hongguan ; Lei, Ningfei ; Gong, Ai Yu ; Chen, Xian Ming ; Hu, Guoku. / Cryptosporidium parvum induces SIRT1 expression in host epithelial cells through downregulating let-7i. In: Human Immunology. 2014 ; Vol. 75, No. 8. pp. 760-765.
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