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• W2889444842 abstract "Granulocyte–macrophage colony-stimulating factor (GM-CSF) has emerged as a crucial cytokine that activates myeloid cells to initiate tissue inflammation. However, the molecular actions of GM-CSF against innate immunity are still poorly characterized. Here, we investigated the in vitro effects of GM-CSF on the activation of human myeloid lineages, neutrophils, and the underlying intracellular signaling mechanism, including inflammasome activation. Human neutrophils were stimulated with GM-CSF in the presence or absence of tofacitinib. The cellular supernatants were analyzed for interleukin-1 beta (IL-1β) and caspase-1 by enzyme-linked immunosorbent assay (ELISA) methods. Pro-IL-1β mRNA expressions in human neutrophils were analyzed by real-time polymerase chain reaction. Protein phosphorylation of neutrophils was assessed by Western blot using phospho-specific antibodies. Stimulation with GM-CSF alone, but not tumor necrosis factor-alpha, was shown to increase the release of IL-1β and cleaved caspase-1 (p20) from human neutrophils. Tofacitinib, which inhibits GM-CSF–induced Janus kinase 2 (Jak2)-mediated signal transduction, completely abrogated GM-CSF–induced IL-1β and caspase-1 (p20) secretion from neutrophils. GM-CSF stimulation also induced pro-IL-1β mRNA expression in neutrophils and induced NLR family pyrin domain-containing 3 (NLRP3) protein expression. Although tofacitinib pretreatment marginally inhibited GM-CSF–induced pro-IL-1β mRNA expression, tofacitinib completely abrogated NLRP3 protein expression in neutrophils. These results indicate that GM-CSF signaling induces NLRP3 expression and subsequent IL-1β production by affecting neutrophils, which may cause the activation of innate immunity. Therefore, GM-CSF is a key regulator of the NLRP3 inflammasome and IL-1β production by activating innate immune cells. This process can be blocked by tofacitinib, which interferes with JAK/STAT signaling pathways." @default.
• W2889444842 created "2018-09-07" @default.
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• W2889444842 date "2018-08-29" @default.
• W2889444842 modified "2023-10-12" @default.
• W2889444842 title "Tofacitinib inhibits granulocyte–macrophage colony-stimulating factor-induced NLRP3 inflammasome activation in human neutrophils" @default.
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• W2889444842 doi "https://doi.org/10.1186/s13075-018-1685-x" @default.
• W2889444842 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6116484" @default.
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• W2889444842 hasPublicationYear "2018" @default.
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