Deletion of the transient receptor potential vanilloid type 1 channel exacerbates renal inflammation induced by lipopolysaccharide in mice

Abstract

To determine the role of the transient receptor potential vanilloid type 1 (TRPV1) channel in the regulation of renal inflammation, lipopolysaccharide (LPS, 3 mg/kg) was intraperitoneally injected into wild type (WT) and TRPV1‐null mutant (TRPV1−/−) mice. Glomerular hypercellularity and red blood cell congestion were found in the kidneys of WT and TRPV1−/− mice 24 hours after LPS injection with greater magnitude in TRPV1−/− mice. Serum creatinine levels were higher in TRPV1−/− than in WT mice 24 hours after LPS injection. Neutrophil infiltration in the kidneys was greater in TRPV1−/− than in WT mice 6 or 24 hours after LPS injection. Serum cytokine levels (TNF‐α, IL‐1β, and IL‐6) and renal chemokine levels (KC and MIP‐2) were higher in TRPV1−/− than in WT mice 6 hours after LPS injection. Western blot analysis showed that renal VCAM‐1 but not ICAM‐1 expression was increased in WT and TRPV1−/− mice 6 hours after LPS injection with greater magnitude in TRPV1−/− mice. Renal NF‐κB activity was elevated further in TRPV1−/− compared to WT mice 6 hours after LPS injection. Thus, TRPV1 gene ablation exacerbates LPS‐induced renal injury, including aggravated renal neutrophil infiltration, chemokine and adhesion molecule levels, and glomerular hypercellularity accompanying with further increased serum creatinine and cytokine levels. Our findings indicate that TRPV1 is activated during LPS challenge and protects against LPS‐induced renal injury possibly via reducing renal inflammatory responses. (Supported in part by the National Natural Science Foundation of China: No. 81170243)