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• W2762851762 abstract "IL-6 is a central mediator of the immediate induction of hepatic acute phase proteins (APP) in the liver during infection and after injury, but increased IL-6 activity has been associated with multiple pathological conditions. In hepatocytes, IL-6 activates JAK1-STAT3 signaling that induces the negative feedback regulator SOCS3 and expression of APPs. While different inhibitors of IL-6-induced JAK1-STAT3-signaling have been developed, understanding their precise impact on signaling dynamics requires a systems biology approach. Here we present a mathematical model of IL-6-induced JAK1-STAT3 signaling that quantitatively links physiological IL-6 concentrations to the dynamics of IL-6-induced signal transduction and expression of target genes in hepatocytes. The mathematical model consists of coupled ordinary differential equations (ODE) and the model parameters were estimated by a maximum likelihood approach, whereas identifiability of the dynamic model parameters was ensured by the Profile Likelihood. Using model simulations coupled with experimental validation we could optimize the long-term impact of the JAK-inhibitor Ruxolitinib, a therapeutic compound that is quickly metabolized. Model-predicted doses and timing of treatments helps to improve the reduction of inflammatory APP gene expression in primary mouse hepatocytes close to levels observed during regenerative conditions. The concept of improved efficacy of the inhibitor through multiple treatments at optimized time intervals was confirmed in primary human hepatocytes. Thus, combining quantitative data generation with mathematical modeling suggests that repetitive treatment with Ruxolitinib is required to effectively target excessive inflammatory responses without exceeding doses recommended by the clinical guidelines." @default.
• W2762851762 created "2017-10-20" @default.
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• W2762851762 date "2017-10-09" @default.
• W2762851762 modified "2023-10-15" @default.
• W2762851762 title "Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib" @default.
• W2762851762 cites W1516657748 @default.
• W2762851762 cites W1577577364 @default.
• W2762851762 cites W1637936532 @default.
• W2762851762 cites W1668039320 @default.
• W2762851762 cites W1855316965 @default.
• W2762851762 cites W1855678235 @default.
• W2762851762 cites W1860244306 @default.
• W2762851762 cites W1964539622 @default.
• W2762851762 cites W1965678323 @default.
• W2762851762 cites W1967723169 @default.
• W2762851762 cites W1967804453 @default.
• W2762851762 cites W1968963646 @default.
• W2762851762 cites W1971636277 @default.
• W2762851762 cites W1972685619 @default.
• W2762851762 cites W1973025942 @default.
• W2762851762 cites W1979056373 @default.
• W2762851762 cites W1979181404 @default.
• W2762851762 cites W1980037861 @default.
• W2762851762 cites W1980568348 @default.
• W2762851762 cites W1982603741 @default.
• W2762851762 cites W1982664065 @default.
• W2762851762 cites W1985193026 @default.
• W2762851762 cites W1985745081 @default.
• W2762851762 cites W1985911638 @default.
• W2762851762 cites W1989181919 @default.
• W2762851762 cites W1996548067 @default.
• W2762851762 cites W1998149586 @default.
• W2762851762 cites W1998238281 @default.
• W2762851762 cites W1999028040 @default.
• W2762851762 cites W1999408263 @default.
• W2762851762 cites W2007338931 @default.
• W2762851762 cites W2010180179 @default.
• W2762851762 cites W2010545917 @default.
• W2762851762 cites W2010681459 @default.
• W2762851762 cites W2016313989 @default.
• W2762851762 cites W2016541161 @default.
• W2762851762 cites W2016966551 @default.
• W2762851762 cites W2017716833 @default.
• W2762851762 cites W2020228681 @default.
• W2762851762 cites W2022121957 @default.
• W2762851762 cites W2022502525 @default.
• W2762851762 cites W2023680965 @default.
• W2762851762 cites W2025421728 @default.
• W2762851762 cites W2027400830 @default.
• W2762851762 cites W2027937017 @default.
• W2762851762 cites W2028034405 @default.
• W2762851762 cites W2028286333 @default.
• W2762851762 cites W2030624761 @default.
• W2762851762 cites W2032828164 @default.
• W2762851762 cites W2039279561 @default.
• W2762851762 cites W2043162503 @default.
• W2762851762 cites W2045478141 @default.
• W2762851762 cites W2045590518 @default.
• W2762851762 cites W2045686436 @default.
• W2762851762 cites W2046878952 @default.
• W2762851762 cites W2049912996 @default.
• W2762851762 cites W2052568980 @default.
• W2762851762 cites W2052731400 @default.
• W2762851762 cites W2054170741 @default.
• W2762851762 cites W2057018521 @default.
• W2762851762 cites W2059044802 @default.
• W2762851762 cites W2059200513 @default.
• W2762851762 cites W2061033316 @default.
• W2762851762 cites W2061035099 @default.
• W2762851762 cites W2067761476 @default.
• W2762851762 cites W2069305891 @default.
• W2762851762 cites W2071825914 @default.
• W2762851762 cites W2071927618 @default.

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