Extracellular IL-33 cytokine, but not endogenous nuclear IL-33, regulates protein expression in endothelial cells

Gautier, Violette; Cayrol, Corinne; Farache, Dorian; Roga, Stéphane; Monsarrat, Bernard; Burlet‐Schiltz, Odile; Peredo, Anne Gonzalez de; Girard, Jean-Philippe

doi:10.1038/srep34255

Cited by 78 publications

(89 citation statements)

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“…Cells were maintained at confluence levels between 90%-100%, as confluency is critical for both LTR-IL-33 and native IL-33 expression [99, 107]. Cells were lysed and subjected to SDS-PAGE and western blotting.…”

Section: Resultsmentioning

confidence: 99%

A novel isoform of IL-33 revealed by screening for transposable element promoted genes in human colorectal cancer

et al. 2017

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Remnants of ancient transposable elements (TEs) are abundant in mammalian genomes. These sequences contain multiple regulatory motifs and hence are capable of influencing expression of host genes. TEs are known to be released from epigenetic repression and can become transcriptionally active in cancer. Such activation could also lead to lineage-inappropriate activation of oncogenes, as previously described in lymphomas. However, there are few reports of this mechanism occurring in non-blood cancers. Here, we re-analyzed whole transcriptome data from a large cohort of patients with colon cancer, compared to matched normal colon control samples, to detect genes or transcripts ectopically expressed through activation of TE promoters. Among many such transcripts, we identified six where the affected gene has described role in cancer and where the TE-driven gene mRNA is expressed in primary colon cancer, but not normal matched tissue, and confirmed expression in colon cancer-derived cell lines. We further characterized a TE-gene chimeric transcript involving the Interleukin 33 (IL-33) gene (termed LTR-IL-33), that is ectopically expressed in a subset of colon cancer samples through the use of an endogenous retroviral long terminal repeat (LTR) promoter of the MSTD family. The LTR-IL-33 chimeric transcript encodes a novel shorter isoform of the protein, which is missing the initial N-terminus (including many conserved residues) of Native IL-33. In vitro studies showed that LTR-IL-33 expression is required for optimal CRC cell line growth as 3D colonospheres. Taken together, these data demonstrate the significance of TEs as regulators of aberrant gene expression in colon cancer.

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Section: Resultsmentioning

confidence: 99%

A novel isoform of IL-33 revealed by screening for transposable element promoted genes in human colorectal cancer

et al. 2017

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“…IL‐33 has been shown to regulate chromatin compaction and NF‐κB transcriptional activity in transfected cells . However, when nuclear IL‐33 was knocked down in primary human endothelial cells, these cells displayed unaltered proteomes and NF‐kB expression as compared to that of the wildtype cells, suggesting that endogenous nuclear IL‐33 does not play a significant role in gene transcription . Furthermore, the mice lacking IL‐33 gene were fertile and did not appear to show gross abnormalities at the resting condition.…”

Section: Biological Functions Of Il‐33mentioning

confidence: 98%

IL‐33: biological properties, functions, and roles in airway disease

Drake

Kita

2017

Immunological Reviews

214

203

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Summary Interleukin (IL)-33 is a key cytokine involved in type 2 immunity and allergic airway diseases. Abundantly expressed in lung epithelial cells, IL-33 plays critical roles in both innate and adaptive immune responses in mucosal organs. In innate immunity, IL-33 and group 2 innate lymphoid cells (ILC2s) provide an essential axis for rapid immune responses and tissue homeostasis. In adaptive immunity, IL-33 interacts with dendritic cells, Th2 cells, follicular T cells, and regulatory T cells, where IL-33 influences the development of chronic airway inflammation and tissue remodeling. The clinical findings that both the IL-33 and ILC2 levels are elevated in patients with allergic airway diseases suggest that IL-33 plays an important role in the pathogenesis of these diseases. IL-33 and ILC2 may also serve as biomarkers for disease classification and to monitor the progression of diseases. In this article, we reviewed the current knowledge of the biology of IL-33 and discussed the roles of the IL-33 in regulating airway immune responses and allergic airway diseases.

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“…Although they are less well characterized, non‐immune cells may also constitute important cellular targets of IL‐33 in vivo. These include endothelial cells, epithelial cells, fibroblasts, astrocytes, and neurons …”

Section: Activation Of St2‐expressing Cellsmentioning

confidence: 99%

“…However, after more than 10 years of research efforts, convincing evidence that endogenous nuclear IL‐33 regulates gene or protein expression is still lacking. Using a global proteomic approach, we recently showed that extracellular IL‐33 cytokine, and not endogenous nuclear IL‐33, regulates protein expression in primary human endothelial cells . High‐resolution mass spectrometry analyses revealed that knockdown of endogenous nuclear IL‐33 using two independent RNA silencing strategies had no reproducible effect on the endothelial cell proteome .…”

Section: Il‐33 a Nuclear Cytokinementioning

confidence: 99%

“…Using a global proteomic approach, we recently showed that extracellular IL‐33 cytokine, and not endogenous nuclear IL‐33, regulates protein expression in primary human endothelial cells . High‐resolution mass spectrometry analyses revealed that knockdown of endogenous nuclear IL‐33 using two independent RNA silencing strategies had no reproducible effect on the endothelial cell proteome . A single protein was modulated on a global scale and it was IL‐33 itself.…”

Section: Il‐33 a Nuclear Cytokinementioning

confidence: 99%

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