TAILIEUCHUNG - Báo cáo khoa học: Modelling and simulating interleukin-10 production and regulation by macrophages after stimulation with an immunomodulator of parasitic nematodes

Parasitic nematodes can downregulate the immune response of their hosts through the induction of immunoregulatory cytokines such as interleukin-10 (IL-10). To define the underlying mechanisms, we measuredin vitro the production of IL-10 in macrophages in response to cystatin fromAcantho-cheilonema viteae, an immunomodulatory protein of filarial nematodes, and developed mathematical models of IL-10 regulation. | ễFEBS Journal Modelling and simulating interleukin-10 production and regulation by macrophages after stimulation with an immunomodulator of parasitic nematodes Ana Sofia Figueiredo1 Thomas Heifer2 Christian Klotz3 Christine Sers4 Susanne Hartmann3 Richard Lucius3 and Peter Hammerstein1 1 Institute for TheoreticalBiology Humboldt University Berlin Germany 2 Research Group Modeling of BiologicalSystems German Cancer Research Center and BioQuant Center Heidelberg Germany 3 Department of Parasitology Berlin Germany 4 Institute of Pathology Universitaetsmedezin Charite Berlin Germany Keywords autocrine crosstalk host-parasite interaction regulation signalling cascades systems biology Correspondence A. S. Figueiredo Institute for Theoretical Biology Humboldt University Invalidenstrasse 43 10115 Berlin Germany Fax 49 30 20938801 Tel 49 30 20938450 E-mail Note The mathematical models described here have been submitted to the Online Cellular Systems Modelling Database and can be accessed at http database figueiredo1 http jjj. database figueiredo2 http database figueiredo3 http database figueiredo4 free of charge Received 5 September 2008 revised 22 February 2009 accepted 21 April2009 doi Parasitic nematodes can downregulate the immune response of their hosts through the induction of immunoregulatory cytokines such as interleukin-10 IL-10 . To define the underlying mechanisms we measured in vitro the production of IL-10 in macrophages in response to cystatin from Acantho-cheilonema viteae an immunomodulatory protein of filarial nematodes and developed mathematical models of IL-10 regulation. IL-10 expression requires stimulation of the mitogen-activated protein kinases extracellular signal-regulated kinase ERK and p38 and we propose that a negative feedback mechanism acting at .

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