Toll-like receptor-7 ligand Imiquimod induces type I interferon and antimicrobial peptides to ameliorate dextran sodium sulfate-induced acute colitis

Inflamm Bowel Dis. 2012 May;18(5):955-67. doi: 10.1002/ibd.21867. Epub 2011 Sep 26.


Background: The pathogenesis of inflammatory bowel disease (IBD) is associated with a dysregulated mucosal immune response. Certain stimulators of innate immunity (CpG DNA or GM-CSF) are reported to be anti-inflammatory in IBD. Toll-like receptor-7 (TLR7) is an important regulator of innate immunity and its activation plays a key role in induction of type I interferon (IFN). The present study tests the hypothesis that the TLR7 agonists Imiquimod has therapeutic efficacy in IBD.

Methods: Acute colitis was induced in Balb/c mice by giving 5% dextran sodium sulfate (DSS) in drinking water for 7 days. Mice were treated with Imiquimod either orally or topically and its therapeutic effects on disease activity were examined. Isolated mouse CD11c+ dendritic cells and human intestinal epithelial cells (HT29, HCT116) were treated with Imiquimod (10 μg/mL) and their susceptibility to intracellular Salmonella typhimurium infection was assessed by gentamicin protection assay.

Results: Oral administration of Imiquimod induced type I IFN expression in the gastrointestinal mucosa and ameliorated DSS-induced acute colitis as assessed by clinical parameters, histology, and mRNA expression of proinflammatory cytokines. Topical administration of Imiquimod also ameliorated DSS colitis by inducing the expression of type I IFN in the colonic mucosa. However, no evidence for a systemic IFN response was observed. Imiquimod treatments to both CD11c+ and intestinal epithelial cells significantly increased expression of antimicrobial peptides (AMPs) and reduced survival of intracellular S. typhimurium.

Conclusions: Imiquimod induces type I IFN and AMP to ameliorate DSS-induced acute colitis and prevents Salmonella survival. Therefore, Imiquimod treatments provide a new therapeutic approach for IBD patients.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Administration, Topical
  • Aminoquinolines / therapeutic use*
  • Animals
  • Antimicrobial Cationic Peptides / metabolism*
  • Biomarkers / metabolism
  • Colitis / chemically induced
  • Colitis / metabolism
  • Colitis / prevention & control*
  • Cytokines / metabolism
  • Dextran Sulfate / toxicity*
  • Female
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / microbiology
  • Gene Expression Profiling
  • Humans
  • Imiquimod
  • Interferon Inducers / therapeutic use*
  • Interferon Type I / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Oligonucleotide Array Sequence Analysis
  • Peroxidase / metabolism
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Salmonella Infections / microbiology
  • Salmonella Infections / mortality
  • Salmonella Infections / prevention & control
  • Salmonella typhimurium
  • Survival Rate
  • Toll-Like Receptor 7 / metabolism*


  • Aminoquinolines
  • Antimicrobial Cationic Peptides
  • Biomarkers
  • Cytokines
  • Interferon Inducers
  • Interferon Type I
  • RNA, Messenger
  • Toll-Like Receptor 7
  • Dextran Sulfate
  • Peroxidase
  • Imiquimod