Open AccessToll‐like receptor‐7 ligand imiquimod induces type I interferon and antimicrobial peptides to ameliorate dextran sodium sulfate‐induced acute colitis
Author(s) -
Sainathan Satheesh K.,
Bishnupuri Kumar S.,
Aden Konrad,
Luo Qizhi,
Houchen Courtney W.,
Anant Shrikant,
Dieckgraefe Brian K.
Publication year - 2012
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1002/ibd.21867
Subject(s) - imiquimod , medicine , immunology , colitis , inflammatory bowel disease , tlr7 , proinflammatory cytokine , immune system , innate immune system , toll like receptor , inflammation , disease
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. (Inflamm Bowel Dis 2011;)