23 research outputs found

    Pulmonary CD14 diminishes lung inflammation by high dose S-LPS, but enhances lung inflammation by low dose S-LPS.

    No full text
    <p>Mice (n = 7–9) were treated intranasally with 10 µg S-LPS (left panel), 1 µg S-LPS (middle panel) or 0.1 µg S-LPS (right panel). Six hours later BALF was isolated and analysed for PMN counts (A–C), TNF levels (D–F) and LIX levels (G–I). Data are mean ± SEM. **, P<0.01; ***, P<0001 versus WT mice.</p

    sCD14 exerts bimodal effects in acute lung inflammation depending on the dose of S-LPS.

    No full text
    <p>WT and CD14KO mice were treated intranasally with 10 µg S-LPS (left panel) or 0.1 µg S-LPS (right panel) and 10 µg sCD14 was administered simultaneously with S-LPS to groups of CD14KO mice. Six hours after LPS (and sCD14) administration, BALF was isolated and analyzed for PMN counts (A, B), TNF levels (C, D) and LIX levels (ER, F). Eight to nine mice were used per group. Data are are mean ± SEM. *, P<0.05; **, P<0.01; ***, P<0001 versus WT mice; ##, P<0.01; ###, P<0.001 versus CD14KO mice.</p

    Pulmonary CD14 partially diminishes lung inflammation by high dose R-LPS, but enhances lung inflammation by low dose R-LPS.

    No full text
    <p>Mice (n = 6–9) were treated intranasally with 10 µg R-LPS (left panel), 1 µg R-LPS (middle panel) or 0.1 µg R-LPS (right panel). Six hours after LPS administration, BALF was isolated and analysed for PMN counts (A–C), TNF levels (D–F) and LIX levels (G–I). Data are mean ± SEM. *, P<0.05; **, P<0.01; ***, P<0001 versus WT mice.</p

    S-LPS induces sCD14 release in the lung in a dose dependent manner.

    No full text
    <p>sCD14 was measured in BALF obtained from WT mice 6 hours after intranasal administration of different doses (10–0.1 µg) of S-LPS. Eight to nine mice were used per group. Data are mean ± SEM. Dotted line represents the mean value of sCD14 in BALF of naive mice.</p

    Role of Tumor Necrosis Factor-α in the Human Systemic Endotoxin-Induced Transcriptome

    Get PDF
    <div><p>TNFα has been implicated in the pathogenesis of various inflammatory diseases. Different strategies to inhibit TNFα in patients with sepsis and chronic inflammatory conditions have shown contrasting outcomes. Although TNFα inhibitors are widely used in clinical practice, the impact of TNFα antagonism on white blood cell gene expression profiles during acute inflammation in humans <i>in vivo</i> has not been assessed. We here leveraged the established model of human endotoxemia to examine the effect of the TNFα antagonist, etanercept, on the genome-wide transcriptional responses in circulating leukocytes induced by intravenous LPS administration in male subjects. Etanercept pre-treatment resulted in a markedly dampened transcriptional response to LPS. Gene co-expression network analysis revealed this LPS-induced transcriptome can be categorized as TNFα responsive and non-responsive modules. Highly significant TNFα responsive modules include NF-kB signaling, antiviral responses and T-cell mediated responses. Within these TNFα responsive modules we delineate fundamental genes involved in epigenetic modifications, transcriptional initiation and elongation. Thus, we provide comprehensive information about molecular pathways that might be targeted by therapeutic interventions that seek to inhibit TNFα activity during human inflammatory diseases.</p></div

    LPS-induced TNFα responsive module genes linked to transcriptional initiation, elongation and epigenetic regulation.

    No full text
    <p>Genes within LPS-induced TNFα responsive co-expression modules possessing epigenetic regulation, transcriptional initiation and elongation properties. kTotal, total connectivity, k. kWithin, intra-modular connectivity. kOut, extra-modular connectivity. <i>log2</i> FC LPS, log2 transformed foldchange for the placebo-treated pre- and post-LPS challenged samples. <i>log2</i> FC LPS+Etan, log2 transformed foldchange for the etanercept-treated pre- and post-LPS challenged samples. Gene names marked in bold type denote module genes identified as top module hub genes.</p
    corecore