1,8-Cineole potentiates IRF3-mediated antiviral response in human stem cells and in an <i>ex vivo</i> model of rhinosinusitis

Müller, Janine; Greiner, Johannes F. W.; Zeuner, Marie Theres; Brotzmann, Viktoria; Schäfermann, Johanna; Wieters, Frederique; Widera, Darius; Sudhoff, Holger; Kaltschmidt, Barbara; Kaltschmidt, Christian

doi:10.1042/cs20160218

Cited by 39 publications

(32 citation statements)

References 46 publications

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“…In this regard, most endogenous ligands studied until now seem to activate NF- κ B signalling via TLR4 [ 41 ], particularly fibrinogen [ 42 ] and HMGB1 [ 43 , 44 ]. U251 cells endogenously express proteins involved in the TLR4 signalling pathway and do not need to be transfected [ 25 , 26 ]. In U251-NF- κ B-GFP-Luc cells, fibrinogen had no effect on NF- κ B-activation whereas HMGB1 seemed to decrease the activity of NF- κ B.…”

Section: Discussionmentioning

confidence: 99%

Development and Characterisation of a Novel NF-κB Reporter Cell Line for Investigation of Neuroinflammation

Zeuner

Vallance

Vaiyapuri

et al. 2017

Mediators of Inflammation

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Aberrant activation of the transcription factor NF-κB, as well as uncontrolled inflammation, has been linked to autoimmune diseases, development and progression of cancer, and neurological disorders like Alzheimer's disease. Reporter cell lines are a valuable state-of-the art tool for comparative analysis of in vitro drug screening. However, a reporter cell line for the investigation of NF-κB-driven neuroinflammation has not been available. Thus, we developed a stable neural NF-κB-reporter cell line to assess the potency of proinflammatory molecules and peptides, as well as anti-inflammatory pharmaceuticals. We used lentivirus to transduce the glioma cell line U251-MG with a tandem NF-κB reporter construct containing GFP and firefly luciferase allowing an assessment of NF-κB activity via fluorescence microscopy, flow cytometry, and luminometry. We observed a robust activation of NF-κB after exposure of the reporter cell line to tumour necrosis factor alpha (TNFα) and amyloid-β peptide [1-42] as well as to LPS derived from Salmonella minnesota and Escherichia coli. Finally, we demonstrate that the U251-NF-κB-GFP-Luc reporter cells can be used for assessing the anti-inflammatory potential of pharmaceutical compounds using Bay11-7082 and IMD0354. In summary, our newly generated cell line is a robust and cost-efficient tool to study pro- and anti-inflammatory potential of drugs and biologics in neural cells.

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Section: Discussionmentioning

confidence: 99%

Development and Characterisation of a Novel NF-κB Reporter Cell Line for Investigation of Neuroinflammation

Zeuner

Vallance

Vaiyapuri

et al. 2017

Mediators of Inflammation

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“…Controls were treated within medium described above without additional stimuli. For gene expression analysis, treatments were performed for 4 h, while a 2 h treatment was done for immunocytochemistry in accordance to our previous studies [22], and a 5 h treatment for western blot.…”

Section: Haematoxylin and Eosin Staining Of Cryostat Sectionsmentioning

confidence: 99%

Stem Cell-Induced Inflammation in Cholesteatoma Is Inhibited by the TLR4 Antagonist LPS-RS

Schürmann

Greiner

Volland-Thurn

et al. 2020

Cells

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Cholesteatoma is a severe non-cancerous lesion of the middle ear characterized by massive inflammation, tissue destruction, and an abnormal growth of keratinized squamous epithelium. We recently demonstrated the presence of pathogenic stem cells within cholesteatoma tissue, unfortunately their potential roles in regulating disease-specific chronic inflammation remain poorly understood. In the presented study, we utilized our established human in vitro cholesteatoma stem cell model for treatments with lipopolysaccharides (LPS), tumor necrosis factor α (TNFα), and the TLR4-antagonist LPS from R. sphaeroides (LPS-RS) followed by qPCR, western blot, and immunocytochemistry. Middle ear cholesteatoma stem cells (ME-CSCs) showed a significantly increased expression of TLR4 accompanied by a significantly enhanced LPS-dependent pro-inflammatory gene expression pattern of TNFα, IL-1α, IL-1ß, IL-6, and IL-8 compared to non-pathogenic control cells. LPS-dependent pro-inflammatory gene expression in ME-CSCs was driven by an enhanced activity of NF-κB p65 leading to a TNFα-mediated feed-forward-loop of pro-inflammatory NF-κB target gene expression. Functional inactivation of TLR4 via the TLR4-antagonist LPS-RS blocked chronic inflammation in ME-CSCs, resulting in a nearly complete loss of IL-1ß, IL-6, and TNFα expression. In summary, we determined that ME-CSCs mediate the inflammatory environment of cholesteatoma via TLR4-mediated NF-κB-signaling, suggesting a distinct role of ME-CSCs as drivers of cholesteatoma progression and TLR4 on ME-CSCs as a therapeutic target.

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“…In response to physical or physiological stress, injury, or infection, inflammation takes place as a key defense process of innate immunity aiming to restore the physiological situation. NF-κB is broadly described to be one of the key transcription factors regarding pro-inflammatory signaling, particularly activated by the presence of pro-inflammatory cytokines (like TNFα or IL-1), lipopolysaccharides (LPS) of the bacterial cell wall [ 17 ], or viral and bacterial nucleic acids [ 18 ]. Recognition of cytokines or LPS species is mediated by the respective receptors, such as TNF receptors or Toll-like microbial pattern recognition receptors (TLRs).…”

Section: Nf-κb In Inflammation and Cancermentioning

confidence: 99%

Subunit-Specific Role of NF-κB in Cancer

et al. 2018

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The transcription factor NF-κB is a key player in inflammation, cancer development, and progression. NF-κB stimulates cell proliferation, prevents apoptosis, and could promote tumor angiogenesis as well as metastasis. Extending the commonly accepted role of NF-κB in cancer formation and progression, different NF-κB subunits have been shown to be active and of particular importance in distinct types of cancer. Here, we summarize overexpression data of the NF-κB subunits RELA, RELB, and c-REL (referring to the v-REL, which is the oncogene of Reticuloendotheliosis virus strain T) as well as of their upstream kinase inhibitor, namely inhibitor of κB kinases (IKK), in different human cancers, assessed by database mining. These data argue against a universal mechanism of cancer-mediated activation of NF-κB, and suggest a much more elaborated mode of NF-κB regulation, indicating a tumor type-specific upregulation of the NF-κB subunits. We further discuss recent findings showing the diverse roles of NF-κB signaling in cancer development and metastasis in a subunit-specific manner, emphasizing their specific transcriptional activity and the role of autoregulation. While non-canonical NF-κB RELB signaling is described to be mostly present in hematological cancers, solid cancers reveal constitutive canonical NF-κB RELA or c-REL activity. Providing a linkage to cancer therapy, we discuss the recently described pivotal role of NF-κB c-REL in regulating cancer-targeting immune responses. In addition, current strategies and ongoing clinical trials are summarized, which utilize genome editing or drugs to inhibit the NF-κB subunits for cancer treatment.

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1,8-Cineole potentiates IRF3-mediated antiviral response in human stem cells and in an ex vivo model of rhinosinusitis

Cited by 39 publications

References 46 publications

Development and Characterisation of a Novel NF-κB Reporter Cell Line for Investigation of Neuroinflammation

Development and Characterisation of a Novel NF-κB Reporter Cell Line for Investigation of Neuroinflammation

Stem Cell-Induced Inflammation in Cholesteatoma Is Inhibited by the TLR4 Antagonist LPS-RS

Subunit-Specific Role of NF-κB in Cancer

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