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Paeoniflorin exerts a nephroprotective effect on concanavalin A-induced damage through inhibition of macrophage infiltration.

Liu C, Cheng Z, Wang Y, Dai X, Zhang J, Xue D - Diagn Pathol (2015)

Bottom Line: The level of expression of C-X-C chemokine receptor type 3 (CXCR3) was analyzed by western blot, immunohistochemical and real-time PCR.PF 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.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.

View Article: PubMed Central - PubMed

Affiliation: Experimental Research Center, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. liucheng0082010@163.com.

ABSTRACT

Background: It 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.

Methods: BALB/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.

Results: PF 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.

Conclusions: Macrophage 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.

No MeSH data available.


Related in: MedlinePlus

Renal sections were stained CXCR3 (red), CXCL11 (green), and DAPI (blue) in non-conA-vehicle, conA-vehicle and conA-PF mice. Arrowhead indicates there is no interaction between CXCR3 and CXCL11. Arrow indicates binding of CXCR3 and CXCL11 and interactions (×400, n = 3). PF (30 mg/kg) was administered orally 2 h before injection of conA or vehicle for 8 h
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Fig7: Renal sections were stained CXCR3 (red), CXCL11 (green), and DAPI (blue) in non-conA-vehicle, conA-vehicle and conA-PF mice. Arrowhead indicates there is no interaction between CXCR3 and CXCL11. Arrow indicates binding of CXCR3 and CXCL11 and interactions (×400, n = 3). PF (30 mg/kg) was administered orally 2 h before injection of conA or vehicle for 8 h

Mentions: Because the number of macrophages is characteristically increased in the conA-vehicle kidneys and macrophages express CXCR3, it was hypothesised that the overproduction of CXCL11 may be involved in macrophage recruitment to the injured kidneys in conA-treated mice. To this end, the presence of CXCR3 with CXCL11 was analysed through immunofluorescence microscopy. As shown in Fig. 7, clear evidence was provided that there was interaction between CXCR3 and CXCL11 in conA-induced damage. In non-conA mice, CXCR3- and CXCL11-positive cells were separated from each other indicating minimal interaction (Fig. 7). Numbers of CXCL11- and CXCR3-positive cells were significantly increased compared with non-conA kidneys 8 h after conA treatment (Fig. 7). CXCL11-positive cells were mostly expressed in tubular epithelial cells, and the CXCR3-positive cells were bound to CXCL11-positive cells. These findings suggest that the production of CXCL11 by the tubular epithelium is responsible for the recruitment of CXCR3-positive cells. PF suppressed the interactions of CXCL11 and CXCR3.Fig. 7


Paeoniflorin exerts a nephroprotective effect on concanavalin A-induced damage through inhibition of macrophage infiltration.

Liu C, Cheng Z, Wang Y, Dai X, Zhang J, Xue D - Diagn Pathol (2015)

Renal sections were stained CXCR3 (red), CXCL11 (green), and DAPI (blue) in non-conA-vehicle, conA-vehicle and conA-PF mice. Arrowhead indicates there is no interaction between CXCR3 and CXCL11. Arrow indicates binding of CXCR3 and CXCL11 and interactions (×400, n = 3). PF (30 mg/kg) was administered orally 2 h before injection of conA or vehicle for 8 h
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4513624&req=5

Fig7: Renal sections were stained CXCR3 (red), CXCL11 (green), and DAPI (blue) in non-conA-vehicle, conA-vehicle and conA-PF mice. Arrowhead indicates there is no interaction between CXCR3 and CXCL11. Arrow indicates binding of CXCR3 and CXCL11 and interactions (×400, n = 3). PF (30 mg/kg) was administered orally 2 h before injection of conA or vehicle for 8 h
Mentions: Because the number of macrophages is characteristically increased in the conA-vehicle kidneys and macrophages express CXCR3, it was hypothesised that the overproduction of CXCL11 may be involved in macrophage recruitment to the injured kidneys in conA-treated mice. To this end, the presence of CXCR3 with CXCL11 was analysed through immunofluorescence microscopy. As shown in Fig. 7, clear evidence was provided that there was interaction between CXCR3 and CXCL11 in conA-induced damage. In non-conA mice, CXCR3- and CXCL11-positive cells were separated from each other indicating minimal interaction (Fig. 7). Numbers of CXCL11- and CXCR3-positive cells were significantly increased compared with non-conA kidneys 8 h after conA treatment (Fig. 7). CXCL11-positive cells were mostly expressed in tubular epithelial cells, and the CXCR3-positive cells were bound to CXCL11-positive cells. These findings suggest that the production of CXCL11 by the tubular epithelium is responsible for the recruitment of CXCR3-positive cells. PF suppressed the interactions of CXCL11 and CXCR3.Fig. 7

Bottom Line: The level of expression of C-X-C chemokine receptor type 3 (CXCR3) was analyzed by western blot, immunohistochemical and real-time PCR.PF 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.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.

View Article: PubMed Central - PubMed

Affiliation: Experimental Research Center, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. liucheng0082010@163.com.

ABSTRACT

Background: It 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.

Methods: BALB/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.

Results: PF 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.

Conclusions: Macrophage 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.

No MeSH data available.


Related in: MedlinePlus