Molecular mechanism of LPS-induced TNF-α biosynthesis in polarized human macrophages

Schilling, Erik; Weiß, Reinhold; Grahnert, Anja; Bitar, Michael; Sack, Ulrich; Hauschildt, Sunna

doi:10.1016/j.molimm.2017.11.026

Cited by 26 publications

(23 citation statements)

References 52 publications

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“…1a, b). The levels of TNF-α produced by M-MΦ were lower than those produced by GM-MΦ under these conditions, consistent with previous observations [8, 29]. …”

Section: Resultssupporting

confidence: 92%

“…As shown in online supplementary Figure S2b IL-6 mRNA levels of M-MФ are always lower than those of GM-MФ while TNF-α mRNA values reached after 30 min and 1 h are similar between the two subsets. At later time points M-MФ express less TNF-α mRNA than GM-MФ supporting a recent publication in which we show that the half-life of TNF-α mRNA in M-MФ is shorter than in GM-MФ [29]. …”

Section: Resultssupporting

confidence: 90%

“…By the use of this method we verified previous data [29, 30] generated by flow cytometry, showing that M-MΦ express higher levels of both TLR4 and CD14 (Fig. 1c).…”

Section: Resultssupporting

confidence: 88%

“…With the exception of p-RelA, these molecules have been shown previously to be expressed at higher levels in M-MΦ than in GM-MΦ [29]. The primary target of the MyD88 canonical pathway is the RelA/p50 NF-κB complex, activation of which enhances transcription of proinflammatory cytokines.…”

Section: Resultsmentioning

confidence: 99%

“…Western blot analysis was carried out as described previously [29]. MΦ (1 × 10 6 /mL) were suspended in RIPA buffer (50 mM Tris, 150 mM NaCl, 1% Nonidet P 40, 0.5% deoxycholate, 0.1% SDS; pH 7.5) supplemented with cOmpleteTM EDTA-free protease inhibitor cocktail (Roche Diagnostics, Mannheim, Germany) and with phosphatase inhibitors (1 mM Na 3 VO 4 and 50 mM NaF).…”

Section: Methodsmentioning

confidence: 99%

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CD14 Counterregulates Lipopolysacharide-Induced Tumor Necrosis Factor-α Production in a Macrophage Subset

et al. 2019

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In response to GM-CSF or M-CSF, macrophages (MΦ) can acquire pro- or anti-inflammatory properties, respectively. Given the importance of CD14 and Toll-like receptor (TLR) 4 in lipopolysaccharide (LPS)-induced signaling, we studied the effect of anti-CD14 antibody mediated CD14 blockade on LPS-induced cytokine production, signal transduction and on the expression levels of CD14 and TLR4 in GM-MΦ and M-MΦ. We found M-MΦ to express higher levels of both surface antigens and to produce more interferon (IFN)-β and interleukin-10, but less tumor necrosis factor (TNF)-α than GM-MΦ. Blockage of CD14 at high LPS concentrations increased the production of proinflammatory cytokines and decreased that of IFN-β in M-MΦ but not in GM-MΦ. We show that phosphorylation states of signaling molecules of the MyD88 (myeloid differentiation primary response 88), TRIF (TIR-domain-containing adapter-inducing IFN-β) and MAPK (mitogen-activated protein kinase) pathways are not altered in any way that would account for the cytokine overshoot reaction. However, CD14 blockage in M-MΦ decreased TLR4 and CD14 expression levels, regardless of the presence of LPS, indicating that the loss of the surface molecules prevented LPS from initiating TRIF signaling. As TNF-α synthesis was even upregulated under these experimental conditions, we suggest that TRIF is normally involved in restricting LPS-induced TNF-α overproduction. Thus, surface CD14 plays a decisive role in the biological response by determining LPS-induced signaling.

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“…1a, b). The levels of TNF-α produced by M-MΦ were lower than those produced by GM-MΦ under these conditions, consistent with previous observations [8, 29]. …”

Section: Resultssupporting

confidence: 92%

Section: Resultssupporting

confidence: 90%

“…By the use of this method we verified previous data [29, 30] generated by flow cytometry, showing that M-MΦ express higher levels of both TLR4 and CD14 (Fig. 1c).…”

Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

CD14 Counterregulates Lipopolysacharide-Induced Tumor Necrosis Factor-α Production in a Macrophage Subset

et al. 2019

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3D Scaffold‐Based Macrophage Fibroblast Coculture Model Reveals IL‐10 Dependence of Wound Resolution Phase

et al. 2019

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Persistent inflammation and impaired repair in dermal wound healing are frequently associated with cell–cell and cell–matrix miscommunication. A direct coculture model of primary human myofibroblasts (MyoFB) and M‐CSF‐differentiated macrophages (M‐Mɸ) in fibrillar three‐dimensional Collagen I (Coll I) matrices is developed to study intercellular interactions. The coculture experiments reveal the number of M‐Mɸ regulated MyoFB dedifferentiation in a dose‐dependent manner. The amount of MyoFB decreases in dependence of the number of cocultured M‐Mɸ, even in the presence of MyoFB‐inducing transforming growth factor β1 (TGF‐β1). Gene expression analysis of matrix proteins (collagen I, collagen III, ED‐A‐fibronectin) confirms the results of an altered MyoFB phenotype. Additionally, M‐Mɸ is shown to be the main source of secreted cytokine interleukin‐10 (IL‐10), which is suggested to affect MyoFB dedifferentiation. These findings indicate a paracrine impact of IL‐10 secretion by M‐Mɸ on the MyoFB differentiation status counteracting the TGF‐β1‐driven MyoFB activation. Hence, the in vitro coculture model simulates physiological situations during wound resolution and underlines the importance of paracrine IL‐10 signals by M‐Mɸ. In sum, the 3D Coll I‐based matrices with a MyoFB–M‐Mɸ coculture form a highly relevant biomimetic model of late stages of wound healing.

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Anti-inflammatory activities of Waltheria indica extracts by modulating expression of IL-1B, TNF-α, TNFRII and NF-κB in human macrophages

et al. 2019

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Molecular mechanism of LPS-induced TNF-α biosynthesis in polarized human macrophages

Cited by 26 publications

References 52 publications

CD14 Counterregulates Lipopolysacharide-Induced Tumor Necrosis Factor-α Production in a Macrophage Subset

CD14 Counterregulates Lipopolysacharide-Induced Tumor Necrosis Factor-α Production in a Macrophage Subset

3D Scaffold‐Based Macrophage Fibroblast Coculture Model Reveals IL‐10 Dependence of Wound Resolution Phase

Anti-inflammatory activities of Waltheria indica extracts by modulating expression of IL-1B, TNF-α, TNFRII and NF-κB in human macrophages

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