Soluble CD14 participates in the response of cells to lipopolysaccharide.

Frey, Elizabeth A.; Miller, David S.; Jahr, T G; Sundan, Anders; Bažil, V; Espevik, Terje; Finlay, B. Brett; Wright, Samuel D.

doi:10.1084/jem.176.6.1665

Cited by 644 publications

(429 citation statements)

References 24 publications

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“…In corroboration with other studies, the up-regulated secretion of soluble CD14 by CSE was detected in our model (Tsutsumi-Ishii and Nagaoka 2003). CD14 is a known activator of inflammation in epithelial cells (Frey et al 1992;Hailman et al 1994;Ulevitch and Tobias 1995;Cario et al 2000). In addition, up-regulation of cystatin C in CSE-exposed cells was also detected.…”

Section: Discussionsupporting

confidence: 92%

Native matrix-based human lung alveolar tissue model in vitro: studies of the reparatory actions of mesenchymal stem cells

et al. 2016

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Studies of lung diseases in vitro often rely on flat, plastic-based monocultures, due to short lifespan of primary cells, complicated anatomy, lack of explants, etc. We hereby present a native 3D model with cues for repopulating epithelial cells. Abilities of mesenchymal stem cells (MSC) to modulate bacterial lipopolysaccharide (LPS) and cigarette smoke-induced injury to pulmonary epithelium were tested in our model. Post-mortem human lung tissue was sliced, cut and decellularized. Resulting matrix pads were reseeded with pulmonary epithelium (A549 line). Markers of the layer integrity and certain secreted proteins in the presence of cigarette smoke extract (CSE) and LPS were assessed via Western blot, ELISA and RT-PCR assays. In parallel, the effects of MSC paracrine factors on exposed epithelial cells were also investigated at gene and protein levels. When cultured on native 3D matrix, A549 cells obtain dual, type I-and II-like morphology. Exposure to CSE and LPS leads to downregulation of several epithelial proteins and suppressed proliferation rate. MSC medium added to the model restores proliferation rate and some of the epithelial proteins, i.e. e-cadherin and beta-catenin. CSE also increases secretion of proinflammatory cytokines by epithelial cells and upregulates transcription factor NFjB. Some of these effects might be counteracted by MSC in our model. We introduce repopulated decellularized lung matrix that highly resembles in vivo situation and is convenient for studies of disease pathogenesis, cytotoxicology and for exploring therapeutic strategies in the human lung context in vitro. MSC paracrine products have produced protecting effects in our model.

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Section: Discussionsupporting

confidence: 92%

Native matrix-based human lung alveolar tissue model in vitro: studies of the reparatory actions of mesenchymal stem cells

et al. 2016

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“…Moreover, R-form LPS induces higher TNF-a responses than S-form in vivo, demonstrating that the different activation capacities of the two LPS chemotypes are also present in vivo. sCD14 provides help during activation of CD14-negative cells by LPS [17,27,[45][46][47][48][49]. Interestingly, as shown here, in the case of murine cells high concentrations of sCD14 are required that are above the normal plasma levels [37].…”

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confidence: 84%

R‐form LPS, the master key to the activation ofTLR4/MD‐2‐positive cells

et al. 2006

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Lipopolysaccharide (endotoxin, LPS) is a major recognition marker for the detection of gram-negative bacteria by the host and a powerful initiator of the inflammatory response to infection. Using S-and R-form LPS from wild-type and R-mutants of Salmonella and E. coli, we show that R-form LPS readily activates mouse cells expressing the signaling receptor Toll-like receptor 4/myeloid differentiation protein 2 (TLR4/MD-2), while the S-form requires further the help of the LPS-binding proteins CD14 and LBP, which limits its activating capacity. Therefore, the R-form LPS under physiological conditions recruits a larger spectrum of cells in endotoxic reactions than S-form LPS. We also show that soluble CD14 at high concentrations enables CD14-negative cells to respond to S-form LPS. The presented in vitro data are corroborated by an in vivo study measuring TNF-a levels in response to injection of R-and S-form LPS in mice. Since the R-form LPS constitutes ubiquitously part of the total LPS present in all wild-type bacteria its contribution to the innate immune response and pathophysiology of infection is much higher than anticipated during the last half century.Supporting information for this article is available at http://www.wiley-vch.de/contents/jc_2040/2006/35593_pdf IntroductionThe interaction of highly conserved microbial constituents with the innate immune system forms the basis of recognition of and reaction against intruding pathogens in mammals. One such constituent is lipopolysaccharide (endotoxin, LPS), a major recognition marker common to gram-negative bacteria [1][2][3], a large group comprising important human pathogens as well as commensals. Thus, the interaction of LPS with cells of the innate immune system leads to the formation and release of endogenous mediators initiating inflammatory and immune responses essential for an antibacterial defense [3,4]. This primarily protective mechanism may become overshadowed by an acute pathophysiological response with the typical clinical symptoms of septic shock that frequently follows the release of inflammatory mediators, such as tumor necrosis factor (TNF)-a during infection [5][6][7].Innate immunity * Both authors contributed equally to this work. [10]. Binding of allergen to its specific IgE on the surface of MC results in an immediate release of preformed pro-inflammatory mediators (e.g., histamine, TNF-a and proteases) from cytoplasmic granules (degranulation) [11] and a later release of de novo synthesized arachidonic acid metabolites and various cytokines like interleukin 6 (IL-6), TNF-a, and chemokines [10,11]. Unlike allergens, LPS induces no degranulation of MC, but like allergens, it stimulates the de novo synthesis and release of cytokines in these cells [9].Activation of cells by LPS is mediated by the Toll-like receptor 4 (TLR4), a member of the highly conserved protein family of TLR, which are specialized in the recognition of microbial components. In mice, defects in TLR4 result in LPS unresponsiveness [12]. For functional interaction with LP...

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“…First, it can facilitate LPS transfer to lipoproteins, preventing over stimulation of the inflammatory response [20,35]. Alternatively, it can facilitate LPS binding to cells that do not express CD14 such as endothelial and epithelial cells, and cause activation of TLR-4 and release of cytokines [9].…”

Section: Introductionmentioning

confidence: 99%

Shedding of sCD14 by bovine neutrophils following activation with bacterial lipopolysaccharide results in down-regulation of IL-8

et al. 2007

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-CD14, the leukocyte co-receptor for lipopolysaccharide (LPS), is important in the response of bovine polymorphonuclear neutrophil leukocytes (PMN) to Gram-negative bacteria. In other species, the expression of CD14 on the surface of PMN was shown to increase after exposure to inflammatory stimuli. These newly expressed molecules may originate from either an intracellular pool or through new gene expression. We sought to characterize bovine PMN cell surface expression and shedding of CD14 molecules, and CD14's effect on secretion of the chemoattractants IL-8 and IL-1β by PMN. Bovine PMN were incubated in RPMI for 20 h at 37 • C with LPS (1, 10, 100 µg/mL). IL-8 release increased with treatment of 1 µg/mL LPS, but decreased 41.5 and 95% at the 10 and 100 µg/mL concentrations of LPS, respectively. In contrast, shedding of CD14 from the surface of PMN only increased at the highest concentration of LPS (100 µg/mL). Secretion of IL-1β was similar regardless of the LPS concentration used to stimulate PMN. The effect of PMN concentration (1 × 10 7 , 2.5 × 10 7 , 5 × 10 7 , and 10 × 10 7 /mL) on CD14 cell surface expression and shedding of IL-8 and IL-1β were also determined. Shedding of CD14 by PMN increased with increasing concentration of PMN after exposure to 0.1 and 10 µg/mL of LPS, while secretion of IL-8 decreased. IL-1β increased at the highest concentration of PMN. The use of real time polymerase chain reaction showed that CD14 mRNA expression was not different between control and LPS-stimulated cells, indicating that the sCD14 came from either membrane bound CD14 or a preformed pool. Our results demonstrate that release of CD14 from PMN suppresses secretion of IL-8, and may be an important regulatory mechanism for controlling excessive migration of PMN into the bovine mammary gland.CD14 / IL-8 / LPS / neutrophil / bovine

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Soluble CD14 participates in the response of cells to lipopolysaccharide.

Cited by 644 publications

References 24 publications

Native matrix-based human lung alveolar tissue model in vitro: studies of the reparatory actions of mesenchymal stem cells

Native matrix-based human lung alveolar tissue model in vitro: studies of the reparatory actions of mesenchymal stem cells

R‐form LPS, the master key to the activation ofTLR4/MD‐2‐positive cells

Shedding of sCD14 by bovine neutrophils following activation with bacterial lipopolysaccharide results in down-regulation of IL-8

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