Human papilloma virus (HPV) 18 proteins E6 and E7 up-regulate ABC transporters in oropharyngeal carcinoma. Involvement of the nonsense-mediated decay (NMD) pathway

Rigalli, Juan Pablo; Reichel, Matthias; Tocchetti, Guillermo Nicolás; Reuter, Tasmin; Dyckhoff, Gerhard; Herold‐Mende, Christel; Weiß, Johanna

doi:10.1016/j.canlet.2018.04.036

Cited by 13 publications

(2 citation statements)

References 30 publications

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“…Direct vascular damage could be an additional trigger for the formation of thrombosis in AGW. It has been described that in HPV-induced tumors ABC-transporters are upregulated [ 52 , 53 ]. An efficient transport of IM to dermal vessels in HPV-associated tumors, inducing vascular damage, could thus be another factor initiating and driving thrombosis.…”

Section: Discussionmentioning

confidence: 99%

Immunothrombotic Mechanisms Induced by Ingenol Mebutate Lead to Rapid Necrosis and Clearance of Anogenital Warts

Braun

Bauer

Németh

et al. 2022

IJMS

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Ingenol mebutate (IM) is highly effective in the treatment of human papillomavirus (HPV)-induced anogenital warts (AGW) leading to fast ablation within hours. However, the exact mode of action is still largely unknown. We performed dermoscopy, in vivo confocal microscopy (CLM), histology, immunohistochemistry, and immunofluorescence to gain insights in mechanisms of IM treatment in AGW. In addition, we used in vitro assays (ELISA, HPV-transfection models) to further investigate in vivo findings. IM treatment leads to a strong recruitment of neutrophils with thrombosis of small skin vessels within 8 h, in a sense of immunothrombosis. In vivo and in vitro analyses showed that IM supports a prothrombotic environment by endothelial cell activation and von Willebrand factor (VWF) secretion, in addition to induction of neutrophil extracellular traps (NETosis). IM superinduces CXCL8/IL-8 expression in HPV-E6/E7 transfected HaCaT cells when compared to non-infected keratinocytes. Rapid ablation of warts after IM treatment can be well explained by the observed immunothrombosis. This new mechanism has so far only been observed in HPV-induced lesions and is completely different from the mechanisms we see in the treatment of transformed keratinocytes in actinic keratosis. Our initial findings indicate an HPV-specific effect, which could be also of interest for the treatment of other HPV-induced lesions. Larger studies are now needed to further investigate the potential of IM in different HPV tumors.

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Section: Discussionmentioning

confidence: 99%

Immunothrombotic Mechanisms Induced by Ingenol Mebutate Lead to Rapid Necrosis and Clearance of Anogenital Warts

Braun

Bauer

Németh

et al. 2022

IJMS

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“…As a member of the same nuclear receptor family as PXR and CAR, chicken xenobiotic receptor (CXR) was first cloned in chicken and was found to be involved in regulation of many genes related to the metabolism of xenobiotics, such as CYP2H1 and CYP2C45 (Baader et al, 2002; Handschin & Meyer, 2000). Recent studies have observed that the post‐transcriptional mechanisms such as mRNA stability have also been shown to be one important way to regulate BCRP expression (Rigalli et al, 2018). Therefore, whether CXR is involved in the regulation of BCRP expression by ivermectin need to be further investigated.…”

Section: Introductionmentioning

confidence: 99%

Ivermectin induces chicken BCRP/ABCG2 expression and function: Involvement of CXR signaling pathway and mRNA stabilization

Wang

et al. 2022

Vet Pharm & Therapeutics

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Ivermectin is a macrocyclic lactone antiparasitic drug widely used in human and veterinary medicine. Previous studies indicated that ivermectin could interact with Pglycoprotein, being a good inducer and substrate; however, it is unknown whether ivermectin affects BCRP of chicken. In this study, we found that ivermectin distinctly affected the expression of BCRP in a time-and concentration-dependent upregulatory way in chicken primary hepatocytes. Subsequent series of experiments showed that the BCRP induction is related with the increase of CXR expression and, promoting CXR translocations to the nucleus and enhancing the stability of Abcg2 mRNA at the post-transcriptional level by ivermectin. Furthermore, we observed that ivermectin also enhanced the stability of Abcg2 mRNA at the post-transcriptional level by Act-D chase assay. We got the similar results by in vivo test that ivermectininduced BCRP and CXR expression in pharmacologically important tissues, and decreased the apparent permeability coefficient of florfenicol (substrate of chicken BCRP). In conclusion, the results indicated that ivermectin could induce chicken BCRP expression and function through the transcriptional CXR signaling pathway and posttranscriptional mRNA stabilization.

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Recent advances in understanding microbial regulation of host multi-drug resistance transporters

Foley

Loew

McCormick

2021

Current Opinion in Physiology

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Human papilloma virus (HPV) 18 proteins E6 and E7 up-regulate ABC transporters in oropharyngeal carcinoma. Involvement of the nonsense-mediated decay (NMD) pathway

Cited by 13 publications

References 30 publications

Immunothrombotic Mechanisms Induced by Ingenol Mebutate Lead to Rapid Necrosis and Clearance of Anogenital Warts

Immunothrombotic Mechanisms Induced by Ingenol Mebutate Lead to Rapid Necrosis and Clearance of Anogenital Warts

Ivermectin induces chicken BCRP/ABCG2 expression and function: Involvement of CXR signaling pathway and mRNA stabilization

Recent advances in understanding microbial regulation of host multi-drug resistance transporters

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