Parasitology

Research Article

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

DEYONG CHUa1a2, MINGZHAN DUa3, XIANGYANG HUa3, QIANG WUa3 and JILONG SHENa1a2 c1

a1 Department of Microbiology and Parasitology, Anhui Key Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, China

a2 Anhui Key Laboratory of Zoonose, Anhui Medical University, Hefei, China

a3 Department of Pathological Anatomy, Anhui Medical University, Hefei, China

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.

(Received January 27 2011)

(Revised March 30 2011)

(Revised May 23 2011)

(Accepted May 27 2011)

(Online publication August 03 2011)

Correspondence:

c1 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

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