OxLDL inhibits LPS-induced IFNβ expression by Pellino3- and IRAK1/4-dependent modification of TANK

Tzieply, Nico; Kühn, Alfred; Morbitzer, Daniel; Namgaladze, Dmitry; Heeg, A; Schaefer, Liliana; Knethen, Andreas von; Jensen, Liselotte E.; Brüne, Bernhard

doi:10.1016/j.cellsig.2012.01.021

Cited by 14 publications

(15 citation statements)

References 33 publications

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“…Additionally, the expression of IFN- β was decreased when RAW264.7 cells were exposed to ox-LDL for 6 h and then gradually restored to baseline. This finding might be due to the induction of TRAF family member-associated NF- κ B activator (TANK) monoubiquitination by ox-LDL and the subsequent suppression of TRIF-dependent IFN- β expression [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

TRIF Regulates BIC/miR-155 via the ERK Signaling Pathway to Control the ox-LDL-Induced Macrophage Inflammatory Response

Guo

et al. 2018

Journal of Immunology Research

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Toll/IL-1R-domain-containing adaptor-inducing IFN-β (TRIF) is an important adaptor for TLR3- and TLR4-mediated inflammatory signaling pathways. Recent studies have shown that TRIF plays a key role in vessel inflammation and atherosclerosis; however, the precise mechanisms are unclear. We investigated the mechanisms of the TRIF-regulated inflammatory response in RAW264.7 macrophages under oxidized low-density lipoprotein (ox-LDL) stimulation. Our data show that ox-LDL induces TRIF, miR-155, and BIC expression, activates the ERK1/2 and SOCS1-STAT3-NF-κB signaling pathways, and elevates the levels of IL-6 and TNF-α in RAW264.7 cells. Knockdown of TRIF using TRIF siRNA suppressed BIC, miR-155, IL-6, and TNF-α expression and inhibited the ERK1/2 and SOCS1-STAT3-NF-κB signaling pathways. Inhibition of ERK1/2 signaling also suppressed BIC and miR-155 expression. These findings suggest that TRIF plays an important role in regulating the ox-LDL-induced macrophage inflammatory response and that TRIF modulates the expression of BIC/miR-155 and the downstream SOCS1-STAT3-NF-κB signaling pathway via ERK1/2. Therefore, TRIF might be a novel therapeutic target for atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

TRIF Regulates BIC/miR-155 via the ERK Signaling Pathway to Control the ox-LDL-Induced Macrophage Inflammatory Response

Guo

et al. 2018

Journal of Immunology Research

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“…While cells from the Pellino3‐deficient mice were shown to respond normally to a range of TLR ligands with respect to the induction of proinflammatory genes and type I IFNs, Pellino3 deficiency led to enhanced TLR3‐induced expression of IFN‐β . With regard to TLR4 signaling, a negative regulatory function for Pellino3 has been described whereby low‐density lipoprotein inhibits TLR4‐mediated IFN‐β expression by activating Pellino3 . More recently, Pellino3 has been shown to negatively regulate TLR2‐ and TLR4‐mediated cell signaling events in macrophages .…”

Section: Discussionmentioning

confidence: 99%

“…63 With regard to TLR4 signaling, a negative regulatory function for Pellino3 has been described whereby low-density lipoprotein inhibits TLR4-mediated IFN-β expression by activating Pellino3. 64 More recently, Pellino3 has been shown to negatively regulate TLR2-and TLR4-mediated cell signaling events in macrophages. 65 Here, we show a negative regulatory role for both isoforms of Pellino3 in terms of NF-ĸB activation and proinflammatory gene induction during the TLR2-mediated response to H. pylori LPS in epithelial cells.…”

Section: Pellino1mentioning

confidence: 99%

Differential modulation of Helicobacter pylori lipopolysaccharide‐mediated TLR2 signaling by individual Pellino proteins

et al. 2016

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“…Furthermore, patients with diffuse large B-cell lymphomas showed a close correlation between increased expression of Pellino-1, increased levels of BCL6, and poor prognosis (106). Pellino-3 was shown as an important molecule regulating OxLDL-mediated inhibition of TLR4-mediated activation of IFN-b in foam cells of atherosclerosis patients (101). These findings indicate that dysregulated expression of Pellino proteins or the presence of SNPs affecting Pellino expression and/or functions could critically underlie pathogenesis of many allergic, infectious, inflammatory diseases and cancer.…”

Section: Pellinos and Diseasementioning

confidence: 94%

“…Macrophages localized to atherosclerotic lesions ingest oxidized low‐density lipoprotein (oxLDL) to yield lipid‐laden foam cells that exhibit increased pro‐inflammatory gene expression but reduced IFNβ induction in response to LPS . OxLDL delivered via the scavenger receptor A1 binds and activates Pellino‐3, promoting mono‐ubiquitination of the adapter TRAF family member‐associated NF‐κB activator (TANK) , leading to impaired recruitment of TBK1 to TRAF3 and inhibition of IFNβ expression . It remains unknown, however, whether pellino‐3 directly ubiquitinates TANK or acts indirectly via activation of another E3 Ub ligase.…”

Section: Pellino‐3 Functionsmentioning

confidence: 99%

E3 ubiquitin ligases Pellinos as regulators of pattern recognition receptor signaling and immune responses

Medvedev

Murphy

Zhou

et al. 2015

Immunological Reviews

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SUMMARY Pellinos are a family of E3 ubiquitin ligases discovered for their role in catalyzing K63-linked polyubiquitination of Pelle, an IL-1 receptor-associated kinase homologue in the Drosophila Toll pathway. Subsequent studies have revealed the central and non-redundant roles of mammalian Pellino-1, Pellino-2 and Pelino-3 in signaling pathways emanating from IL-1 receptors, Toll-like receptors, NOD-like receptors, T- and B-cell receptors. While Pellinos ability to interact with many signaling intermediates suggested their scaffolding roles, recent findings in mice expressing ligase-inactive Pellinos demonstrated the importance of Pellino ubiquitin ligase activity. Cell-specific functions of Pellinos have emerged, e.g., Pellino-1 being a negative regulator in T-lymphocytes and a positive regulator in myeloid cells, and details of molecular regulation of receptor signaling by various members of the Pellino family have been revealed. In this review, we have summarized current information about Pellino-mediated regulation of signaling by pattern recognition receptors, T-cell and B-cell receptors and TNF receptors, and discuss Pellino’s role in sepsis and infectious diseases, as well as in autoimmune, inflammatory and allergic disorders. We also provide our perspective on the potential of targeting Pellinos with peptide- or small molecule-based drug compounds as a new therapeutic approach for septic shock and autoimmune pathologies.

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OxLDL inhibits LPS-induced IFNβ expression by Pellino3- and IRAK1/4-dependent modification of TANK

Cited by 14 publications

References 33 publications

TRIF Regulates BIC/miR-155 via the ERK Signaling Pathway to Control the ox-LDL-Induced Macrophage Inflammatory Response

TRIF Regulates BIC/miR-155 via the ERK Signaling Pathway to Control the ox-LDL-Induced Macrophage Inflammatory Response

Differential modulation of Helicobacter pylori lipopolysaccharide‐mediated TLR2 signaling by individual Pellino proteins

E3 ubiquitin ligases Pellinos as regulators of pattern recognition receptor signaling and immune responses

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