Table 4. Therapeutic challenges of PRR manipulation for murine colitis models.
| PRRs | Agonist/antagonist | Model of IBD used | Major effect |
|---|---|---|---|
| TLR2 | Agonist (Pam3CSK4)52, 54 | Acute DSS colitis, chronic MDR1α−/− | Prevention and treatment. Strengthen epithelial barrier. Increase TFF3 |
| TLR3 | Agonist (poly(I:C))141 | Acute DSS colitis | Prevention. Involvement of Type I IFN? |
| TLR4 | Antagonist (1A6)121 Antagonist (CRX-526)120 | Acute DSS colitis, chronic MDR1α−/− T-cell transfer colitis | Prevention. Blocking acute inflammatory infiltrate. Blocking cytokine responses |
| TLR5 | Agonist (flagellin)142 | Acute DSS colitis | Prevention if it is administered intraperitoneally |
| TLR9 | Agonist (CpG-ODN)143, 144 Antagonist (AV-ODN)60 | Acute DSS colitis, TNBS colitis, chronic DSS colitis, IL-10−/−, T-cell transfer colitis | Prevention. Anti-apoptotic effect. Immuno-modulatory effect. Induction of tolerance. Blocking host response to luminal bacterial CpG |
| NOD2 | Agonist (MDP)123 | Acute DSS colitis, TNBS colitis | Downregulation of multiple TLR responses |
AV-ODN, adenoviral oligodeoxynucleotides; CpG-ODN, cytosine-phosphate-guanosine oligodeoxynucleotides; DSS, dextran sulfate sodium; IBD, inflammatory bowel disease; IFN, interferon; IL, interleukin; MDP, muramyl dipeptide; MDR1, multidrug resistance; poly(I:C), polyinosinic-polycytidylic acid; PRR, pattern-recognition receptor; TFF3, trefoil factor; TLR, Toll-like receptor; TNBS, 2,4,6-trinitrobenzenesulfonic acid.