Regulation of cytokine expression in murine macrophages stimulated by excretory/secretory products from Trichinella spiralis in vitro.

Abstract

Trichinella spiralis is a zoonotic nematode and food borne parasite and infection with T. spiralis leads to suppression of the host immune response and other immunopathologies. The excretory/secretory (ES) products of T. spiralis play important roles in the process of immunomodulation. However, the mechanisms and related molecules are unknown. Macrophages, a target for immunomodulation by the helminth parasite, play a critical role in initiating and modulating the host immune response to parasite infection. In this study, we examined the effect of ES products from different stages of T. spiralis on modulating J774A.1 macrophage activities. ES products from different stages of T. spiralis reduced the capacity of macrophages to express pro-inflammatory cytokines (tumor necrosis factor α, interleukin-1β , interleukin-6 , and interleukin-12) in response to lipopolysaccharide (LPS) challenge. However, only ES products from 3-day-old adult worms and 5-day-old adult worms/new-born larvae significantly inhibited inducible nitric oxide synthase gene expression in LPS-induced macrophages. In addition, ES products alone boosted the expression of anti-inflammatory cytokines interleukin-10 and transforming growth factor-β and effector molecule arginase 1 in J774A.1 macrophages. Signal transduction studies showed that ES products significantly inhibited nuclear factor-κB translocation into the nucleus and the phosphorylation of both extracellular signal-regulated protein kinase 1/2 and p38 mitogen-activated protein kinase in LPS-stimulated J774A.1 macrophages. These results suggest that ES products regulate host immune response at the macrophage level through inhibition of pro-inflammatory cytokines production and induction of macrophage toward the alternative phenotype, which maybe important for worm survival and host health.

• Authors: Xue Bai, Xiuping Wu, Xuelin Wang, Zhenhong Guan, Fei Gao, Jianli Yu, Lu Yu, Bin Tang, Xiaolei Liu, Yanxia Song, Xinrui Wang, Blaga Radu, Pascal Boireau, Feng Wang, Mingyuan Liu
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 360 Issue 1-2 Pg. 79-88 (Jan 2012) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 21909996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media, Conditioned
• Cytokines
• Lipopolysaccharides
• NF-kappa B
• Nitric Oxide Synthase Type II
• Mitogen-Activated Protein Kinases

Topics

• Active Transport, Cell Nucleus (drug effects)
• Animals
• Cell Line
• Cell Nucleus (metabolism)
• Cell Survival (drug effects)
• Culture Media, Conditioned (pharmacology)
• Cytokines (genetics, metabolism)
• Gene Expression (drug effects)
• Gene Expression Regulation
• Host-Parasite Interactions
• Inflammation (chemically induced, metabolism)
• Larva (metabolism)
• Lipopolysaccharides
• Macrophages (drug effects, enzymology, metabolism)
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Phosphorylation
• Rats
• Rats, Wistar
• Trichinella spiralis (metabolism)