Repression of interferon β-regulated cytokines by the JAK1/2 inhibitor ruxolitinib in inflammatory human macrophages

Febvre-James, Marie; Lecureur, Valérie; Augagneur, Yoann; Mayati, Abdullah; Fardel, Olivier

doi:10.1016/j.intimp.2017.11.032

Cited by 34 publications

(19 citation statements)

References 51 publications

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“…Furthermore, it has been shown that neutrophils have a key role in the pathogenesis of acute GVHD (26, 67, 68). As for macrophages, ruxolitinib was shown to prevent the up-regulation of various proinflammatory cytokines in human macrophages (69). Ruxolitinib impairs cytokine expression by inhibiting LPS/TLR4/IFN beta signaling pathway.…”

Section: Cellular Targets Of the Immunosuppressive Activity Of Ruxolimentioning

confidence: 99%

Mechanisms Underlying the Anti-inflammatory and Immunosuppressive Activity of Ruxolitinib

et al. 2019

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The JAK-STAT signaling pathway plays a central role in signal transduction in hematopoietic cells, as well as in cells of the immune system. The occurrence in most patients affected by myeloproliferative neoplasms (MPNs) of driver mutations resulting in the constitutive activation of JAK2-dependent signaling identified the deregulated JAK-STAT signal transduction pathway as the major pathogenic mechanism of MPNs. It also prompted the development of targeted drugs for MPNs. Ruxolitinib is a potent and selective oral inhibitor of both JAK2 and JAK1 protein kinases. Its use in patients with myelofibrosis is associated with a substantial reduction in spleen volume, attenuation of symptoms and decreased mortality. With growing clinical experience, concerns about infectious complications, and increased risk of B-cell lymphoma, presumably caused by the effects of JAK1/2 inhibition on immune response and immunosurveillance, have been raised. Evidence shows that ruxolitinib exerts potent anti-inflammatory and immunosuppressive effects. Cellular targets of ruxolitinib include various components of both the innate and adaptive immune system, such as natural killer cells, dendritic cells, T helper, and regulatory T cells. On the other hand, immunomodulatory properties have proven beneficial in some instances, as highlighted by the successful use of ruxolitinib in corticosteroid-resistant graft vs. host disease. The objective of this article is to provide an overview of published evidence addressing the key question of the mechanisms underlying ruxolitinib-induced immunosuppression.

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Section: Cellular Targets Of the Immunosuppressive Activity Of Ruxolimentioning

confidence: 99%

Mechanisms Underlying the Anti-inflammatory and Immunosuppressive Activity of Ruxolitinib

et al. 2019

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“…Reference Effects of ruxolitinib Reference CBL Downregulated after treatment in severe cases (PBMC) [14] Inhibits CBL mutant Pluripotent Stem Cells [90] CXCL10 Upregulated in COVID-19 patients PBMC (compared to normal PBMC) and elevated blood level in severe patients [32,49,52] Downregulates the expression level in macrophages [91] IL10 Upregulated in COVID-19 patients PBMC (compared to normal PBMC)and elevated blood level in severe patients [10,11,49,50,53,14,15,16,18,19,24,27,31] Decreases secretion in macrophages [92] IL18 Upregulated COVID-19 patients PBMC (compared to normal PBMC) [49] Downregulates IL18 expression levels in lymphoblasts [69] IL2 Elevated blood level in severe patients [31] Reduces IL2 levels in T cells [73] IL2RB Downregulated after treatment in severe cases (PBMC) [14] Inhibits JAK/STAT pathway activating IL2RB mutant Ba/F3 cells [93] MCL1 Downregulated after treatment in severe cases (PBMC) [14] Downregulates expression level in lymphoblasts [94]…”

Section: Genes Regulation In Covid-19mentioning

confidence: 99%

The potential of JAK/STAT pathway inhibition by ruxolitinib in the treatment of COVID-19

Bağca

Avcı

2020

Cytokine & Growth Factor Reviews

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Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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“…For pharmacological inhibition of the Janus kinase (JAK)/signal transducer and activator of transduction (STAT) signaling pathway, 10 µM ruxolitinib phosphate (catalog #CS-0326, Chem Scene LLC, Monmouth Junction, NJ, USA) was added to the media. The concentration of ruxolitinib phosphate was determined according to a previous publication (Febvre-James et al, 2018).…”

Section: Bp Explant Culturementioning

confidence: 99%

Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture Model

Matsunaga

Kita

Yamamoto

et al. 2020

Front. Cell. Neurosci.

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Sensorineural hearing loss is a common disability often caused by the loss of sensory hair cells in the cochlea. Hair cell (HCs) regeneration has long been the main target for the development of novel therapeutics for sensorineural hearing loss. In the mammalian cochlea, hair cell regeneration is limited, but the auditory epithelia of non-mammalian organisms retain the capacity for hair cell regeneration. In the avian basilar papilla (BP), supporting cells (SCs), which give rise to regenerated hair cells, are usually quiescent. Hair cell loss induces both direct transdifferentiation and mitotic division of supporting cells. Here, we established an explant culture model for hair cell regeneration in chick basilar papillae and validated it for investigating the initial phase of hair cell regeneration. The histological assessment demonstrated hair cell regeneration via direct transdifferentiation of supporting cells. Labeling with 5-ethynyl-2′-deoxyuridine (EdU) revealed the occurrence of mitotic division in the supporting cells at specific locations in the basilar papillae, while no EdU labeling was observed in newly generated hair cells. RNA sequencing indicated alterations in known signaling pathways associated with hair cell regeneration, consistent with previous findings. Also, unbiased analyses of RNA sequencing data revealed novel genes and signaling pathways that may be related to the induction of supporting cell activation in the chick basilar papillae. These results indicate the advantages of our explant culture model of the chick basilar papillae for exploring the molecular mechanisms of hair cell regeneration.

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Repression of interferon β-regulated cytokines by the JAK1/2 inhibitor ruxolitinib in inflammatory human macrophages

Cited by 34 publications

References 51 publications

Mechanisms Underlying the Anti-inflammatory and Immunosuppressive Activity of Ruxolitinib

Mechanisms Underlying the Anti-inflammatory and Immunosuppressive Activity of Ruxolitinib

The potential of JAK/STAT pathway inhibition by ruxolitinib in the treatment of COVID-19

Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture Model

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