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

Abstract

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.

• Authors: Deyong Chu, Mingzhan Du, Xiangyang Hu, Qiang Wu, Jilong Shen
• Journal: Parasitology (Parasitology) Vol. 138 Issue 10 Pg. 1259-71 (Sep 2011) ISSN: 1469-8161 [Electronic] England
• PMID: 21810309 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzoates
• Bridged-Ring Compounds
• Glucosides
• Interleukin-13
• Monoterpenes
• STAT6 Transcription Factor
• Stat6 protein, mouse
• peoniflorin
• Hyaluronic Acid
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Jak2 protein, mouse
• Janus Kinase 2
• Arg1 protein, mouse
• Arginase

Topics

• Animals
• Arginase (antagonists & inhibitors, genetics, metabolism)
• Benzoates (administration & dosage, therapeutic use)
• Bridged-Ring Compounds (administration & dosage, therapeutic use)
• Female
• Gene Expression
• Glucosides (administration & dosage, therapeutic use)
• Granuloma (etiology, metabolism, parasitology, pathology, prevention & control)
• Humans
• Hyaluronic Acid (analysis)
• Interleukin-13 (antagonists & inhibitors, genetics, metabolism)
• Janus Kinase 2 (antagonists & inhibitors, genetics, metabolism)
• Kupffer Cells (cytology, drug effects, metabolism)
• Liver (drug effects, metabolism, parasitology, pathology)
• Liver Cirrhosis (etiology, metabolism, parasitology, pathology, prevention & control)
• Macrophage Activation (drug effects)
• Macrophages (cytology, drug effects, metabolism)
• Mice
• Mice, Inbred BALB C
• Monoterpenes
• Nitric Oxide Synthase Type II (antagonists & inhibitors, genetics, metabolism)
• Phosphorylation (drug effects)
• STAT6 Transcription Factor (antagonists & inhibitors, genetics, metabolism)
• Schistosoma japonicum (physiology)
• Schistosomiasis japonica (complications, metabolism, parasitology, pathology, prevention & control)