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Paeoniflorin attenuates schistosomiasis japonica-associated liver fibrosis through inhibiting alternative activation of macrophages

Published online by Cambridge University Press:  03 August 2011

DEYONG CHU
Affiliation:
Department of Microbiology and Parasitology, Anhui Key Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, China Anhui Key Laboratory of Zoonose, Anhui Medical University, Hefei, China
MINGZHAN DU
Affiliation:
Department of Pathological Anatomy, Anhui Medical University, Hefei, China
XIANGYANG HU
Affiliation:
Department of Pathological Anatomy, Anhui Medical University, Hefei, China
QIANG WU
Affiliation:
Department of Pathological Anatomy, Anhui Medical University, Hefei, China
JILONG SHEN*
Affiliation:
Department of Microbiology and Parasitology, Anhui Key Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, China Anhui Key Laboratory of Zoonose, Anhui Medical University, Hefei, China
*
*Corresponding author: Department of Microbiology and Parasitology; Anhui Key Laboratory of Microbiology and Parasitology, AMU; Anhui Key Laboratory of Zoonoses, AMU, No. 81, Meishan Road, Hefei, Anhui, China. Tel/Fax: +86 551 5113863. E-mail: jlshen@ahmu.edu.cn

Summary

Interleukin (IL)-13 and alternatively activated macrophages (AAMs) play an important role in liver granuloma and fibrosis of schistosomiasis. Paeoniflorin (PAE, C23H28O11) has been reported to have an anti-hepatic fibrosis effect in schistosomiasis; however, the mechanism has not been fully elucidated. In this study, we measured serum hyaluronic acid (HA) concentrations, liver granuloma diameter and volume density, fibrosis degree and expressions of IL-13, arginase-1 (ARG-1), nitric oxide synthase-2 (NOS-2), and phosphorylated signal transducer and activator of transcription 6 (p-STAT6) in mice liver of schistosomiasis. Then we detected expressions of specific biomarkers of AAMs and activity of Arg-1 in Kupffer cells (KCs) from infected and PAE-treated mice, or in KCs from uninfected mice, but exposed to rIL-13 in vitro. Finally, we observed expression of IL-13 signalling molecules in KCs and secretion of IL-13 from lymphocytes of infected and PAE-treated mice. Our results showed that during schistosomiasis, IL-13 expression and secretion increased with liver macrophages activated alternatively. PAE not only directly inhibited alternative activation of macrophages via reducing the phosphorylations of janus-activated kinase 2 (JAK2) and/or STAT6, leading to reduction of AAMs-related markers and Arg-1 activity, but also indirectly suppressed alternative activation of macrophages through decreasing secretion of IL-13. PAE might be a promising prophylactic agent for hepatic granuloma and fibrosis of schistosomiasis japonica.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2011

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Paeoniflorin attenuates schistosomiasis japonica-associated liver fibrosis through inhibiting alternative activation of macrophages
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