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LPS‐induced TNFα production by macrophages is suppressed by a soluble product from the adult tapeworm, Hymenolepis diminuta
Author(s) -
Johnston Michael,
Catarino Michael,
Wang Arthur,
Cho Suzanne,
Phan Van,
McKay Derek
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.674.7
Subject(s) - macrophage , hymenolepis diminuta , immune system , biology , immunology , tlr4 , cytokine , tumor necrosis factor alpha , receptor , mannose receptor , lymphokine , macrophage activating factor , biochemistry , in vitro , helminths , cestoda
Helminth parasites actively regulate their hosts’ immune response. Thus parasite‐derived molecules have the potential to be used to skew or suppress immune responses in humans as a way to treat immunopathology and disease. Seeking to exploit this we hypothesized that a product from H. diminuta would suppress macrophage activation. The human THP‐1 macrophage cell line was treated with LPS ± a high molecular weight fraction (HMWf: >50kDa) of H. diminuta . The HMWf reduced macrophage activation as assessed by TNFα and IL‐6 production in a time‐ and dose‐dependent manner. The ability of THP‐1 cells to phagocytose E. coli was unaffected by HMWf. RT‐PCR for the mannose receptor (up‐regulated on anti‐inflammatory macrophages) and Toll‐Like Receptor 4 (LPS receptor) mRNA revealed no differences between groups, indicating that the HMWf does not induce an alternatively activated macrophage or interfere with TLR4 expression. A HMWf from excretory/secretory (E/S) products from H. diminuta also reduced LPS‐induced TNFα production. The ability of the adult worm HMWf or the E/S products to block TNFα production by THP‐1 cells was insensitive to boiling or treatment with proteinase K. We conclude that a heat stable HMW product(s) from H. diminuta is a potent suppressor of macrophage activity, and that purification of this factor could serve as a template for drugs to block inflammatory disease. Funded by CCFC, CIHR & CAG.