Abstract
BackgroundIt is well established that macrophage infiltration is involved in concanavalin A (conA)-induced liver injury. However, the role of macrophages in conA-induced renal injury remains unknown. The aims of this study were to investigate macrophage infiltration in conA-induced renal injury and determine whether paeoniflorin (PF) could inhibit macrophage infiltration into the kidney.MethodsBALB/C mice were pre-treated with or without PF 2 h (h) before conA injection. At 8 h after con A injection, all the mice were sacrificed; The liver and kidney histology were studied. The renal CD68 expression was detected by immunohistochemical and real-time PCR analysis. The level of expression of C-X-C chemokine receptor type 3 (CXCR3) was analyzed by western blot, immunohistochemical and real-time PCR. The pathophysiological involvement of CXCR3 in macrophage infiltration were investigated using dual-colour immunofluorescence microscopy.ResultsPF administration significantly reduced the elevated serum levels of alanine transaminase (ALT), blood urea nitrogen (BUN), creatinine (Cr) and the severity of liver and renal damage compared with that in the conA-vehicle group. PF administration inhibited the increase in renal IL1β mRNA expression and concentration. Furthermore, immunohistochemical analysis showed that macrophages secreted CXCR3 in the kidneys of the conA-vehicle mice. Immunofluorescence microscopy demonstrated CXCR3 bound tightly to C-X-C motif ligand 11 (CXCL11) in the kidneys of the conA-vehicle mice and showed that PF treatment could suppress CXCR3/CXCL11 over-activation.ConclusionsMacrophage infiltration was a notable pathological change in the kidneys of conA-treated mice. PF administration attenuated conA-induced renal damage, at least in part, by inhibiting the over-activated CXCR3/CXCL11 signal axis.
Highlights
It is well established that macrophage infiltration is involved in concanavalin A-induced liver injury
Suppressed concanavalin A (conA)-induced liver injury in PF-treated mice To test the effects of PF on conA-induced mouse hepatitis, PF (6 mg/kg, 30 mg/kg, or 150 mg/kg) was intraperitoneally administered
Light microscopy examination showed that 8 h after intravenous injection of conA (15 mg/kg body weight) severe liver histopathology was induced, i.e. extensive areas of hepatocyte necrosis and marked sinusoidal hyperaemia associated with haemorrhage
Summary
It is well established that macrophage infiltration is involved in concanavalin A (conA)-induced liver injury. The aims of this study were to investigate macrophage infiltration in conA-induced renal injury and determine whether paeoniflorin (PF) could inhibit macrophage infiltration into the kidney. ConA-induced liver injury is a well-established mouse model used to detect immune cell-mediated acute hepatitis, and closely resembles the pathology of human autoimmune hepatitis [1]. ConA-induced liver injury is characterised by a marked increase in plasma alanine transaminase (ALT) levels from 8 to 24 h after injection, as well as simultaneous hepatic infiltration by CD4+ T immune cells, natural killer T cells (NKT), Kupffer cells, Paeoniflorin (PF), a monoterpene glycoside, is the principal bioactive component of Radix Paeoniae Rubra, a traditional Chinese herbal medicine [5]. It has been hypothesised that the kidney is damaged in conA-induced hepatitis, and PF could reduce conA-induced renal damage by inhibiting macrophage infiltration. This study describes a newly discovered effect of PF and a previously unknown functional mechanism in renal diseases
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