https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7255 Sat 24 Mar 2018 08:33:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23783 F/F mice. This regulation by IL-6 in gp130^F/F mice requires hyperactivation of the latent transcription factor signal transducer and activator of transcription (STAT) 3 via the IL-6 signaling receptor subunit gp130. However, the identity of LPS/TLR4-responsive inflammatory signaling pathways and gene networks, which are modulated by IL-6 (via gp130/STAT3), and the extent to which the tissue and cellular context of this regulation contributes to LPS-induced endotoxic shock in gp130^F/F mice, are unknown. We report here that in LPS-treated macrophages from gp130^F/F mice, gp130 hyperactivation upregulated the LPS-induced expression of inflammatory mediators downstream of Janus kinase (JAK)/STAT, nuclear factor κ-light-chain-enhancer of activated B cells, interferon regulatory factor and c-Jun N-terminal kinase/p38 mitogen-activated protein kinase pathways. Notably, however, LPS administration to bone marrow chimeras indicated that heightened LPS/TLR4 signaling in haemopoietic-derived gp130^F/F immune cells is dispensable for the hypersensitivity of gp130^F/F mice to LPS-induced endotoxemia. To understand the molecular consequences of gp130 hyperactivity in non-haemopoietic tissue on LPS-induced systemic inflammation, global gene expression profiling of livers from LPS-treated gp130^F/F mice was performed and identified 264 hepatic LPS-responsive genes, which are differentially regulated by hyperactive gp130 signaling. Collectively, the substantial transcriptional reprogramming of LPS-responsive genes in gp130^F/F mice emphasizes non-haemopoietic gp130 signaling as a key regulator of systemic inflammatory responses during LPS-induced endotoxemia.]]> Fri 21 Oct 2016 15:57:28 AEDT ]]>