A novel structural class of potent inhibitors of NF-κB activation: structure–activity relationships and biological effects of 6-aminoquinazoline derivatives

Tobe, Masanori; Isobe, Yoshiaki; Tomizawa, Hideyuki; Nagasaki, Takahiro; Takahashi, Hirotada; Hayashi, Hideya

doi:10.1016/s0968-0896(03)00438-3

Cited by 66 publications

(64 citation statements)

References 17 publications

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“…7c), as expected if HSP70 limits pro-inflammatory signalling that is beneficial to the virus. We also tested the effect of QNZ, an inhibitor of NF-kB activation (Tobe et al, 2003) and found that, consistent with the effect of TNFa treatment, QNZ reduced Ad5 late gene expression in both cell types (Fig. 7d).…”

Section: Possible Roles Of Hsp70 During Ad5 Infectionsupporting

confidence: 63%

Promyelocytic leukemia protein isoform II inhibits infection by human adenovirus type 5 through effects on HSP70 and the interferon response

Atwan

Wright

Woodman

et al. 2016

Journal of General Virology

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Promyelocytic leukemia (PML) proteins have been implicated in antiviral responses but PML and associated proteins are also suggested to support virus replication. One isoform, PML-II, is required for efficient transcription of interferon and interferon-responsive genes. We therefore investigated the PML-II contribution to human adenovirus 5 (Ad5) infection, using shRNAmediated knockdown. HelaDII cells showed a 2-3-fold elevation in Ad5 yield, reflecting an increase in late gene expression. This increase was found to be due in part to the reduced innate immune response consequent upon PML-II depletion. However, the effect was minor because the viral E4 Orf3 protein targets and inactivates this PML-II function. The major benefit to Ad5 in HelaDII cells was exerted via an increase in HSP70; depletion of HSP70 completely reversed this replicative advantage. Increased Ad5 late gene expression was not due either to the previously described inhibition of inflammatory responses by HSP70 or to effects of HSP70 on major late promoter or L4 promoter activity, but might be linked to an observed increase in E1B 55K, as this protein is known to be required for efficient late gene expression. The induction of HSP70 by PML-II removal was specific for the HSPA1B gene among the HSP70 gene family and thus was not the consequence of a general stress response. Taken together, these data show that PML-II, through its various actions, has an overall negative effect on the Ad5 lifecycle.

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Section: Possible Roles Of Hsp70 During Ad5 Infectionsupporting

confidence: 63%

Promyelocytic leukemia protein isoform II inhibits infection by human adenovirus type 5 through effects on HSP70 and the interferon response

Atwan

Wright

Woodman

et al. 2016

Journal of General Virology

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“…2C). We also treated WT OCPs with a recently developed nonspecific NF-B inhibitor (31,36) and found that it also inhibited RANKL-induced VEGF-C expression in a dosedependent manner (Fig. 2D).…”

Section: Nf-b Regulates Rankl-induced Expression Of Vegf-c Bymentioning

confidence: 90%

VEGF-C, a Lymphatic Growth Factor, Is a RANKL Target Gene in Osteoclasts That Enhances Osteoclastic Bone Resorption through an Autocrine Mechanism

Zhang

Guo

et al. 2008

Journal of Biological Chemistry

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“…In some experiments, keratinocytes were first treated for 24 h with a cell-permeable quinazoline compound (6-amino-4-(4-phenoxyphenylethylamino) quinazoline) (10 nM; Calbiochem) which inhibits NF-B transcriptional activation (18). Cells were then stimulated for an additional 24 h with combinations of IFN-␥ (R&D Systems), TNF-␣ (R&D Systems), IL-4 (R&D Systems), and IL-13 (R&D Systems).…”

Section: Keratinocyte Culturesmentioning

confidence: 99%

IL-4 and IL-13 Negatively Regulate TNF-α- and IFN-γ-Induced β-Defensin Expression through STAT-6, Suppressor of Cytokine Signaling (SOCS)-1, and SOCS-3

Albanesi

Fairchild

Madonna

et al. 2007

The Journal of Immunology

177

160

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Human β-defensins (HBDs) are a major class of antimicrobial peptides that play an important role in the innate immune response, however, the induction and regulation of these antimicrobial peptides is not well understood. We demonstrate here that stimulation of keratinocytes with TNF-α/IFN-γ induces HBD-2 and HBD-3 by activating STAT-1 and NF-κB signaling. We further demonstrate that IL-4 and IL-13 activate STAT-6 and induce the suppressors of cytokine signaling (SOCS)-1 and -3. This interferes with STAT-1 and NF-κB signaling, thereby inhibiting TNF-α/IFN-γ-mediated induction of HBD-2 and HBD-3. These data suggest that targeting the STAT-1-signaling pathway or suppressor of cytokine signaling expression enhances β-defensin expression and represents a new therapeutic strategy for reduction of infection in human diseases associated with β-defensin deficiency.

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A novel structural class of potent inhibitors of NF-κB activation: structure–activity relationships and biological effects of 6-aminoquinazoline derivatives

Cited by 66 publications

References 17 publications

Promyelocytic leukemia protein isoform II inhibits infection by human adenovirus type 5 through effects on HSP70 and the interferon response

Promyelocytic leukemia protein isoform II inhibits infection by human adenovirus type 5 through effects on HSP70 and the interferon response

VEGF-C, a Lymphatic Growth Factor, Is a RANKL Target Gene in Osteoclasts That Enhances Osteoclastic Bone Resorption through an Autocrine Mechanism

IL-4 and IL-13 Negatively Regulate TNF-α- and IFN-γ-Induced β-Defensin Expression through STAT-6, Suppressor of Cytokine Signaling (SOCS)-1, and SOCS-3

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