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To define the underlying mechanisms, we measured <jats:italic>in\u2003vitro<\/jats:italic> the production of IL\u201010 in macrophages in response to cystatin from <jats:italic>Acanthocheilonema viteae<\/jats:italic>, an immunomodulatory protein of filarial nematodes, and developed mathematical models of IL\u201010 regulation. IL\u201010 expression requires stimulation of the mitogen\u2010activated protein kinases extracellular signal\u2010regulated kinase (ERK) and p38, and we propose that a negative feedback mechanism, acting at the signalling level, is responsible for transient IL\u201010 production that can be followed by a sustained plateau. Specifically, a model with negative feedback on the ERK pathway via secreted IL\u201010 accounts for the experimental data. Accordingly, the model predicts sustained phospho\u2010p38 dynamics, whereas ERK activation changes from transient to sustained when the concentration of immunomodulatory protein of <jats:italic>Acanthocheilonema viteae<\/jats:italic> increases. We show that IL\u201010 can regulate its own production in an autocrine fashion, and that ERK and p38 control IL\u201010 amplitude, duration and steady state. We also show that p38 affects ERK via secreted IL\u201010 (autocrine crosstalk). These findings demonstrate how convergent signalling pathways may differentially control kinetic properties of the IL\u201010 signal.<\/jats:p>","DOI":"10.1111\/j.1742-4658.2009.07068.x","type":"journal-article","created":{"date-parts":[[2009,5,18]],"date-time":"2009-05-18T15:10:11Z","timestamp":1242659411000},"page":"3454-3469","source":"Crossref","is-referenced-by-count":13,"title":["Modelling and simulating interleukin\u201010 production and regulation by macrophages after stimulation with an immunomodulator of parasitic nematodes"],"prefix":"10.1111","volume":"276","author":[{"given":"Ana 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