Table 1.
In vivo studies on the role of TLRs and MyD88 in I/R injury
| Publications | TLRs studied | Beneficial or unbeneficial against intestinal I/R injury | Findings |
|---|---|---|---|
| Tatum, J Pediatr Surg | TLR2 TLR4 | beneficial | Neonatal mice deficient in TLR4, either alone or in concert with TLR2, were more susceptible to intestinal mucosal damage. |
| Watanabe, PLoS One | TLR2 | unbeneficial | TLR2−/− mice exhibited less severe mucosal injury and decreased MPO and TNF-α and ICAM-1 mRNA expression. |
| Aprahamian, Pediatr Crit Care Med | TLR2 | beneficial | In TLR2−/− mice, intestinal injury scores increased and the expression of IFN-γ, IL-4, and IL-6 mRNA decreased. |
| Chen, Shock | TLR4 | beneficial | Lipopolysaccharide, a TLR4 ligand, decreased mesenteric I/R injury-induced gut damage through TNF-α signaling. |
| Zhu, Oncotarget | TLR4 | unbeneficial | TLR4 mutation suppressed histological injuries and reduced cytokine expression in the intestine (TNF-α, IL-6, IL-1β, and NF-κB). |
| Pope, Mol Immunol | TLR4 | unbeneficial | TLR4-deficient mice sustained less damage and inflammation after I/R than wild-type mice. |
| Moses, J Leukoc Biol | TLR4 MyD88 | unbeneficial | The absence of TLR4 or MyD88 attenuated local mucosal damage and significantly decreased cytokine and eicosanoid secretion, including PGE2 production. |
| Wang, World J Gastroenterol | TLR4 MyD88 | unbeneficial | Blocking HMGB1 and MyD88 reduced the levels of inflammatory cytokines (NF-κB, p65, and TNF-α) in serum. |
| Kojima, J Surg Res | TLR4 | unbeneficial | Anti-HMGB1 antibody treatment significantly reduced the damage and improved the 48-h survival rates. |
| Slone, Am J Clin Exp Immunol | TLR9 | no effect | TLR9 is not required for I/R-induced injury or inflammation of the intestine. |
| Watanabe, Am J Physiol Gastrointest Liver Physiol | MyD88 | beneficial | The MyD88 signaling pathway inhibited I/R injury in the small intestine by inducing COX-2 expression. |
TLR, Toll-like receptor; MyD88, myeloid differentiation primary response 88; I/R, ischemia/reperfusion; TNF, tumor necrosis factor; MPO, myeloperoxidase; ICAM, intercellular adhesion molecule; IFN, interferon; IL, interleukin; HMGB, high mobility group box; COX, cyclooxygenase.