Date: Monday, June 13, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
We have previously shown that tubular epithelial cells play a central role in regulating ischemia-reperfusion kidney injury (K-IRI). Tubular epithelial cells damaged by hypoxic insult release high levels of high-mobility group box 1 (HMGB1) protein, an endogenous damage-associated molecular pattern (DAMP), which in turn induces secretion of CCR5 ligands through TLR2 in an autocrine manner. NK cells are recruited to the kidney in response to CCR ligands and stimulate CD137L in tubular epithelial cell via their cell surface CD137. CD137L signaling results in production of CXCR2 ligands which are required for recruitment of neutrophils. These results suggest that the sequential signaling events occurring in tubular epithelial cells during K-IRI course are targets for therapeutic intervention of K-IRI. In this study, we showed that infusion of MyD88 peptide inhibitor through renal vein just before induction of K-IRI was highly effective in reducing K-IRI: it inhibits CCR2 ligands, preventing infiltration of NK cells into the kidney; subsequent recruitment of neutrophils was impaired and general renal inflammation induced by ischemia-reperfusion was markedly decreased. In vitro assays showed that MyD88 inhibitor effectively blocked secretion of CCR5 ligands promoted by TLR2 stimulation. Taken together, our results indicate that infusion of TLR2 inhibitor into the kidney before transplantation may contribute to reduce K-IRI that commonly occurs in transplanted kidneys.
CITATION INFORMATION: Cho H, Lee J, Kim H, Han Y, Kwon B, Park S, Park K. Local Infusion of MyD88 Inhibitor Inhibits Ischemia-Reperfusion Kidney Injury. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Cho H, Lee J, Kim H, Han Y, Kwon B, Park S, Park K. Local Infusion of MyD88 Inhibitor Inhibits Ischemia-Reperfusion Kidney Injury. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/local-infusion-of-myd88-inhibitor-inhibits-ischemia-reperfusion-kidney-injury/. Accessed March 6, 2021.
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