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Paeoniflorin inhibits TGF-β1-mediated collagen production by Schistosoma japonicum soluble egg antigen in vitro

Published online by Cambridge University Press:  24 May 2007

D. CHU
Affiliation:
Institute of Clinical Pharmacology, Anhui Medical Universityand the Key Laboratory of Antiinflammatory-immunopharmacology, Anhui, China Institute of Zoonoses of Anhui Medical University and the Key Laboratory of Gene Resource Utilization for Severe Diseases (Anhui Medical University), Ministry of Education of China
Q. LUO
Affiliation:
Institute of Zoonoses of Anhui Medical University and the Key Laboratory of Gene Resource Utilization for Severe Diseases (Anhui Medical University), Ministry of Education of China
C. LI
Affiliation:
Institute of Zoonoses of Anhui Medical University and the Key Laboratory of Gene Resource Utilization for Severe Diseases (Anhui Medical University), Ministry of Education of China
Y. GAO
Affiliation:
Institute of Clinical Pharmacology, Anhui Medical Universityand the Key Laboratory of Antiinflammatory-immunopharmacology, Anhui, China Institute of Zoonoses of Anhui Medical University and the Key Laboratory of Gene Resource Utilization for Severe Diseases (Anhui Medical University), Ministry of Education of China
L. YU
Affiliation:
Institute of Clinical Pharmacology, Anhui Medical Universityand the Key Laboratory of Antiinflammatory-immunopharmacology, Anhui, China Institute of Zoonoses of Anhui Medical University and the Key Laboratory of Gene Resource Utilization for Severe Diseases (Anhui Medical University), Ministry of Education of China
W. WEI
Affiliation:
Institute of Clinical Pharmacology, Anhui Medical Universityand the Key Laboratory of Antiinflammatory-immunopharmacology, Anhui, China
Q. WU
Affiliation:
Department of Pathology, Anhui Medical University
J. SHEN*
Affiliation:
Institute of Clinical Pharmacology, Anhui Medical Universityand the Key Laboratory of Antiinflammatory-immunopharmacology, Anhui, China Institute of Zoonoses of Anhui Medical University and the Key Laboratory of Gene Resource Utilization for Severe Diseases (Anhui Medical University), Ministry of Education of China
*
*Corresponding author: Institute of Zoonoses of Anhui Medical University and the Key Laboratory of Gene Resource Utilization for Severe Diseases, No. 81, Meishan Road, Hefei, Anhui, China. Tel./Fax: +86 551 5161057. E-mail: jlshen@ahmu.edu.cn

Summary

The main pathological characteristics of hepatic fibrosis in schistosomiasis are the proliferation of hepatic stellate cells (HSCs) and the deposition of collagen type I (Col I) and collagen type III (Col III). Transforming growth factor beta-1 (TGF-β1) plays an important role in hepatic fibrosis. Paeoniflorin (PAE) has been reported to have immunoregulatory effects; however, the mechanism of its anti-hepatic fibrosis in S. japonicum has not been elucidated. In the present study, we found that mouse peritoneal macrophages (PMφs) stimulated by soluble egg antigen (SEA) of S. japonicum could secrete TGF-β1, and the TGF-β1 in the peritoneal macrophage-conditioned medium (PMCM) could induce proliferation of HSCs and secretion of Col I and III. We selected PMCM at 1:2 dilution as the optimum PMCM (OPMCM). Then we treated HSCs pre-incubated with OPMCM with PAE, and found that the inhibition of HSC proliferation or Col I and III production were closely correlated with the concentration of PAE. Further investigation found that PAE significantly decreased the Smad3 transcription and phosphorylation in HSCs stimulated by OPMCM. In conclusion, SEA plays a key role in hepatic fibrosis by inducing TGF-β1 from PMφs. PAE can exert anti-fibrogenic effects by inhibiting HSCs proliferation and down-regulating Smad3 expression and phosphorylation through TGF-β1 signalling.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2007

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Paeoniflorin inhibits TGF-β1-mediated collagen production by Schistosoma japonicum soluble egg antigen in vitro
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