Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Diagnostic Pathology
Published in: Diagnostic Pathology 1/2015

Open Access 01-12-2015 | Research

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

Authors: Cheng Liu, Zhuoan Cheng, Yunman Wang, Xiuqin Dai, Jie Zhang, Dongying Xue

Published in: Diagnostic Pathology | Issue 1/2015

Login to get access

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.
Literature
1.
Wahl C, Wegenka UM, Leithauser F, Schirmbeck R, Reimann J. IL-22-Dependent Attenuation of T Cell-Dependent (ConA) Hepatitis in Herpes Virus Entry Mediator Deficiency. J Immunol. 2009;182(8):4521–8.PubMedCrossRef
2.
Xu L, Qi J, Zhao P, Liang X, Ju Y, Liu P, et al. T cell immunoglobulin- and mucin-domain-containing molecule-4 attenuates concanavalin A-induced hepatitis by regulating macrophage. J Leukocyte Biol. 2010;88(2):329–36.PubMedCrossRef
3.
Feng D, Mei Y, Wang Y, Zhang B, Wang C, Xu L. Tetrandrine protects mice from concanavalin A-induced hepatitis through inhibiting NF-κB activation. Immunol Lett. 2008;121(2):127–33.PubMedCrossRef
4.
Nakajima H, Takagi H, Horiguchi N, Toyoda M, Kanda D, Otsuka T, et al. Lack of macrophage migration inhibitory factor protects mice against concanavalin A-induced liver injury. Liver Int. 2006;26(3):346–51.PubMedCrossRef
5.
Wu YM, Jin R, Yang L, Zhang J, Yang Q, Guo YY, et al. Phosphatidylinositol 3 kinase/protein kinase B is responsible for the protection of paeoniflorin upon H2O2-induced neural progenitor cell injury. Neuroscience. 2013;240:54–62.PubMedCrossRef
6.
Jiang Z, Chen W, Yan X, Bi L, Guo S, Zhan Z. Paeoniflorin protects cells from GalN/TNF- -induced apoptosis via ER stress and mitochondria-dependent pathways in human L02 hepatocytes. Acta Biochim Biophys Sin. 2014;46(5):357–67.PubMedCrossRef
7.
Zhang J, Dou W, Zhang E, Sun A, Ding L, Wei X, et al. Paeoniflorin abrogates DSS-induced colitis via a TLR4-dependent pathway. AJP: Gastrointestinal and Liver Physiology. 2014;306(1):G27–36.
8.
Li X, Shen J, Zhong Z, Peng J, Wen H, Li J, et al. Paeoniflorin ameliorates schistosomiasis liver fibrosis through regulating IL-13 and its signalling molecules in mice. Parasitology. 2010;137(08):1213–25.PubMedCrossRef
9.
Chen X, Liu C, Lu Y, Yang Z, Lv Z, Xu Q, et al. Paeoniflorin regulates macrophage activation in dimethylnitrosamine-induced liver fibrosis in rats. BMC Complement Altern Med. 2012;12:254.PubMedCentralPubMedCrossRef
10.
Liu C, Tao Q, Sun M, Wu JZ, Yang W, Jian P, et al. Kupffer cells are associated with apoptosis, inflammation and fibrotic effects in hepatic fibrosis in rats. Lab Invest. 2010;90(12):1805–16.PubMedCrossRef
11.
Colvin RA, Campanella GSV, Sun J, Luster AD. Intracellular Domains of CXCR3 That Mediate CXCL9, CXCL10, and CXCL11 Function. J Biol Chem. 2004;279(29):30219–27.PubMedCrossRef
12.
Liang J, Zhang B, Shen R, Liu J, Gao M, Li Y, et al. Preventive effect of halofuginone on concanavalin A-induced liver fibrosis. PLoS One. 2013;8(12):e82232.PubMedCentralPubMedCrossRef
13.
Shimizu A, Ishii E, Masuda Y, Sato A, Piao H, Kunugi S, et al. Renal inflammatory changes in acute hepatic failure-associated acute kidney injury. Am J Nephrol. 2013;37(4):378–88.PubMedCrossRef
14.
Galmarini D, Tarenzi L, Cantaluppi G, Fassati LR, Mauri A, Zanandrea G, et al. Acute hepatic failure and renal damage. Experimental and clinical studies. Minerva Med. 1978;69(21):1417–26.PubMed
15.
Mizuguchi Y, Kawada N, Kobayashi K, Morisawa S, Yamada J. Serotonin and tryptamine metabolism in the acute hepatic failure model--changes in tryptophan and its metabolites in the liver, brain, kidney and serum. Nihon Shokakibyo Gakkai Zasshi. 1990;87(3):780–9.PubMed
16.
Shao X, Qian Y, Xu C, Hong B, Xu W, Shen L, et al. The protective effect of intrasplenic transplantation of Ad-IL-18BP/IL-4 gene-modified fetal hepatocytes on ConA-induced hepatitis in mice. PLoS One. 2013;8(3):e58836.PubMedCentralPubMedCrossRef
17.
Jiang N, Zhang X, Zheng X, Chen D, Siu K, Wang H, et al. A novel in vivo siRNA Delivery system specifically targeting liver cells for protection of ConA-induced fulminant hepatitis. PLoS One. 2012;7(9):e44138.PubMedCentralPubMedCrossRef
18.
Abraham AP, Ma FY, Mulley WR, Ozols E, Nikolic-Paterson DJ. Macrophage infiltration and renal damage are independent of matrix metalloproteinase 12 in the obstructed kidney. Nephrology. 2012;17(4):322–9.PubMedCrossRef
19.
Hatano M, Sasaki S, Ohata S, Shiratsuchi Y, Yamazaki T, Nagata K, et al. Effects of Kupffer cell-depletion on Concanavalin A-induced hepatitis. Cell Immunol. 2008;251(1):25–30.PubMedCrossRef
20.
Assis DN, Leng L, Du X, Zhang CK, Grieb G, Merk M, et al. The role of macrophage migration inhibitory factor in autoimmune liver disease. Hepatology. 2014;59(2):580–91.PubMedCentralPubMedCrossRef
21.
Nakamura K, Ito T, Yoneda M, Takamoto S, Nakade Y, Okamoto S, et al. Antithrombin III prevents concanavalin A-induced liver injury through inhibition of macrophage inflammatory protein-2 release and production of prostacyclin in mice. J Hepatol. 2002;36(6):766–73.PubMedCrossRef
22.
Okamoto S, Yokohama S, Yoneda M, Haneda M, Nakamura K. Macrophage inflammatory protein-1alpha plays a crucial role in concanavalin A-induced liver injury through induction of proinflammatory cytokines in mice. Hepatol Res. 2005;32(1):38–45.PubMedCrossRef
23.
Cantaluppi V, Quercia AD, Dellepiane S, Ferrario S, Camussi G, Biancone L. Interaction between systemic inflammation and renal tubular epithelial cells. Nephrol Dial Transpl. 2014;29:2004.CrossRef
24.
Kim CS, Joo SY, Lee KE, Choi JS, Bae EH, Ma SK, et al. Paricalcitol attenuates 4-hydroxy-2-hexenal-Induced Inflammation and epithelial-mesenchymal transition in human renal proximal tubular epithelial cells. PLoS One. 2013;8(5):e63186.PubMedCentralPubMedCrossRef
25.
Bondar C, Araya RE, Guzman L, Rua EC, Chopita N, Chirdo FG. Role of CXCR3/CXCL10 axis in immune cell recruitment into the small intestine in celiac disease. PLoS One. 2014;9(2):e89068.PubMedCentralPubMedCrossRef
26.
Zhou H, Bian D, Jiao X, Wei Z, Zhang H, Xia Y, et al. Paeoniflorin protects against lipopolysaccharide-induced acute lung injury in mice by alleviating inflammatory cell infiltration and microvascular permeability. Inflamm Res. 2011;60(10):981–90.PubMedCrossRef
Metadata
Title
Paeoniflorin exerts a nephroprotective effect on concanavalin A-induced damage through inhibition of macrophage infiltration
Authors
Cheng Liu
Zhuoan Cheng
Yunman Wang
Xiuqin Dai
Jie Zhang
Dongying Xue
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2015
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-015-0347-4

Other articles of this Issue 1/2015

Diagnostic Pathology 1/2015 Go to the issue

Methodology

Validation of a locked nucleic acid based wild-type blocking PCR for the detection of EGFR exon 18/19 mutations

Case Report

Paraspinal extramedullary hematopoiesis in hereditary spherocytosis with a concurrent follicular lymphoma: case report and review of the literature

Case Report

A GRIA2 and PAX8-positive renal solitary fibrous tumor with NAB2-STAT6 gene fusion

Research

RETRACTED ARTICLE: HMGB1: a novel protein that induced platelets active and aggregation via Toll-like receptor-4, NF-κB and cGMP dependent mechanisms

Research

Evaluation of diagnostic criteria for IgG4-related tubulointerstitial nephritis

Case Report

Malignant neuroendocrine tumour of the appendix in childhood with loco-regional lymph node invasion