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Effets régulateurs du ruxolitinib sur l'expression de marqueurs de l'inflammation et de protéines de détoxication des médicaments

Abstract : Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor currently used for the treatment of myeloproliferative neoplasms. It shows anti-inflammatory properties, but the involved molecular and cellular mechanisms remain poorly understood. The regulatory effects of ruxolitinib on the expression of inflammatory markers and drug-detoxifying proteins were investigated in different cellular models through these studies. In human macrophages, ruxolitinib represses the expression of inflammatory cytokines secondarily induced by the IFNβ signalling pathway, in response to LPS. Similarly, ruxolitinib inhibits the expression of acute phase proteins induced in human hepatocytes and in the HepaRG cell line. It also notably represses the expression of CRP secondarily induced by the IL6 signalling pathway, in response to LPS. Moreover, ruxolitinib restores the expression and activity of hepatic drug-detoxifying proteins inhibited in inflammatory conditions. In these studies, ruxolitinib is shown to be efficient at concentrations which can be reached in patients. Altogether, these results show that, firstly, as its anti-inflammatory properties are shown throughout different cellular models, ruxolitinib could be interesting for the treatment of various inflammatory pathologies. Also, clinical use could restore hepatic detoxification capacity for patients suffering from inflammatory diseases and therefor require dose adjustments for associated drugs which metabolism could be regulated by inflammation.
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Submitted on : Tuesday, March 17, 2020 - 11:47:11 AM
Last modification on : Wednesday, September 9, 2020 - 5:38:13 AM
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  • HAL Id : tel-02509881, version 1


Marie Febvre-James. Effets régulateurs du ruxolitinib sur l'expression de marqueurs de l'inflammation et de protéines de détoxication des médicaments. Médecine humaine et pathologie. Université Rennes 1, 2019. Français. ⟨NNT : 2019REN1B043⟩. ⟨tel-02509881⟩



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