Differential effects of statins on inflammatory interleukin-8 and antimicrobial peptide human b-defensin 2 responses in salmonella-infected intestinal epithelial cells

Fu Chen Huang*, Shun Chen Huang

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

13 Scopus citations

Abstract

Alternative therapies are needed to reduce the use of antibiotics and incidence of drug-resistant Salmonellosis. Previous studies have revealed important roles of statins in regulating innate immunity. Therefore, we investigated the effects of statins on innate immunity in Salmonella-infected intestinal epithelial cells (IECs), which are involved in mucosal innate immunity. SW480 cells and Akt siRNA-or vitamin D receptor (VDR) siRNA-transfected SW480 cells were infected by wild-type S. Typhimurium strain SL1344 in the presence or absence of statins. The mRNA or protein expression was analyzed by real-time quantitative PCR or western blot analysis, respectively. Simvastatin or fluvastatin caused IL-8 (interleukin-8) suppression, but increased hBD-2 mRNA expression in Salmonella-infected SW480 cells. Both statins enhanced phosphorylated Akt and VDR expressions. Akt or VDR knockdown by siRNA counteracted the suppressive effect of simvastatin on IL-8 expression, whereas VDR knockdown diminished the enhanced hBD-2 expression in Salmonella-infected SW480 cells. Therefore, we observed differential regulation of statins on inflammatory IL-8 and anti-microbial hBD-2 expressions in Salmonella-infected IECs via PI3K/Akt signaling and VDR protein expression, respectively. The enhanced activity of antimicrobial peptides by statins in Salmonella-infected IECs could protect the host against infection, and modulation of pro-inflammatory responses could prevent the detrimental effects of overwhelming inflammation in the host.

Original languageEnglish
Article number1650
JournalInternational Journal of Molecular Sciences
Volume19
Issue number6
DOIs
StatePublished - 02 06 2018

Bibliographical note

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Antimicrobial peptide
  • Cytokines
  • Innate immunity
  • Intestinal epithelia
  • Salmonella
  • Statins

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