Toll Like Receptor 2 Induces Kidney Inflammation Via Myd88/Nf-Kappa B Signaling Pathway

Objective: Septic acute kidney injury (AKI) can be caused by an inflammatory process in the kidney. We previously have revealed that TLR2 is over expressed in podocytes of lipopolysaccharide (LPS)-induced septic AKI mice. In the current study, we aimed to investigate the significance of TLR2 overexpression in podocytes on AKI pathogenesis and underlying mechanisms. Methods: In vitro, podocyte cell line with or without LPS treatment was tested for the expression of TLR2 by Western blot, IL-6 and TNF-alpha by RT-PCR and ELISA, MyD88 and p65 by RT-PCR and Western blot, respectively. Subcellular location of MyD88 and p65 was determined by immunofluorescence. In vivo, AKI mice were induced by LPS, and the expression of TLR2, MyD88 and p65 were determined by immunohistochemistry and the expression of IL-6 and TNF-alpha was measured by ELISA. Results: In vitro podocyte cell line study showed that LPS treatment significantly increased the expression of TLR2, inflammatory cytokines IL-6 and TNF-alpha, and signaling pathway proteins MyD88 and p65. Moreover, a nearly full translocation of p65 from cytoplasm to nucleus was observed in LPS-treated podocytes. Of note, all the above changes induced by LPS treatment could be strongly suppressed by TLR2 knock-down. In vivo experiment on LPS-induced septic AKI mice confirmed that TLR2 overexpression lead to inflammatory cytokines IL-6 and TNF-alpha expression as well as the elevation of signaling pathway factors MyD88 and p65. Conclusion: Our study has revealed that TLR2 overexpression in podocytes enhances inflammatory cytokines expression through MyD88/NF-kappa B signaling pathway, consequently promoting AKI pathogenesis.