Negative Regulation of Tec Kinase Alleviates LPS-Induced Acute Kidney Injury in Mice via theTLR4NF-κB Signaling Pathway

Abstract EN

Tec kinase is an important mediator in inflammatory immune response that enhances the activity of neutrophils and macrophages.

However, information on its function in lipopolysaccharide- (LPS-) induced acute kidney injury (AKI) is limited.

This study is aimed at determining whether Tec kinase was a regulator in AKI.

An AKI model in mice was successfully established using intraperitoneal LPS.

Results showed that the serum levels of creatinine (Cr), blood urea nitrogen (BUN), and cystatin-C (Cys-C) increased after intraperitoneal LPS injection.

Renal tissue sustained significantly severe injury as measured by pathological scores.

Pretreatment with LFM-A13 improved the function of the kidney in mice and decreased the renal injury score.

Enzyme-linked immunosorbent assay showed that LFM-A13 significantly reduced the release of IL-1β and TNF-α in mice exposed to LPS.

LFM-A13 can evidently abrogate the expression of Tec protein, MyD88, TLR4, NF-κB p65, and Tec’s phosphorylated protein as determined by Western blot.

Immunohistochemistry analysis revealed that LFM-A13 markedly downregulated the expression of Tec kinase in renal tubular epithelial cells.

In vitro, Tec kinase protein was expressed highly in NRK-52E cells after LPS exposure.

Tec-siRNA also decreased IL-1β and TNF-α production and obviously abolished phospho-p65 and phospho-IκBα expression in NRK-52E cell stimulated by LPS; however, Tec-siRNA increased the IκBα level.

Altogether, these data suggested that Tec kinase can be a modulating protein in AKI through TLR4/NF-κB activation.