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IPSE, a parasite-derived, host immunomodulatory infiltrin protein, alleviates resiniferatoxin-induced bladder pain
The transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor is an important mediator of nociception and its expression is enriched in nociceptive neurons. TRPV1 signaling has been implicated in bladder pain and is a potential analgesic target. Resiniferatoxin is the most po...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756320/ https://www.ncbi.nlm.nih.gov/pubmed/33342372 http://dx.doi.org/10.1177/1744806920970099 |
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author | Ishida, Kenji Mbanefo, Evaristus C Le, Loc Lamanna, Olivia Pennington, Luke F Finkel, Julia C Jardetzky, Theodore S Falcone, Franco H Hsieh, Michael H |
author_facet | Ishida, Kenji Mbanefo, Evaristus C Le, Loc Lamanna, Olivia Pennington, Luke F Finkel, Julia C Jardetzky, Theodore S Falcone, Franco H Hsieh, Michael H |
author_sort | Ishida, Kenji |
collection | PubMed |
description | The transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor is an important mediator of nociception and its expression is enriched in nociceptive neurons. TRPV1 signaling has been implicated in bladder pain and is a potential analgesic target. Resiniferatoxin is the most potent known agonist of TRPV1. Acute exposure of the rat bladder to resiniferatoxin has been demonstrated to result in pain-related freezing and licking behaviors that are alleviated by virally encoded IL-4. The interleukin-4-inducing principle of Schistosoma mansoni eggs (IPSE) is a powerful inducer of IL-4 secretion, and is also known to alter host cell transcription through a nuclear localization sequence-based mechanism. We previously reported that IPSE ameliorates ifosfamide-induced bladder pain in an IL-4- and nuclear localization sequence-dependent manner. We hypothesized that pre-administration of IPSE to resiniferatoxin-challenged mice would dampen pain-related behaviors. IPSE indeed lessened resiniferatoxin-triggered freezing behaviors in mice. This was a nuclear localization sequence-dependent phenomenon, since administration of a nuclear localization sequence mutant version of IPSE abrogated IPSE’s analgesic effect. In contrast, IPSE’s analgesic effect did not seem IL-4-dependent, since use of anti-IL-4 antibody in mice given both IPSE and resiniferatoxin did not significantly affect freezing behaviors. RNA-Seq analysis of resiniferatoxin- and IPSE-exposed bladders revealed differential expression of TNF/NF-κb-related signaling pathway genes. In vitro testing of IPSE uptake by urothelial cells and TRPV1-expressing neuronal cells showed uptake by both cell types. Thus, IPSE’s nuclear localization sequence-dependent therapeutic effects on TRPV1-mediated bladder pain may act on TRPV1-expressing neurons and/or may rely upon urothelial mechanisms. |
format | Online Article Text |
id | pubmed-7756320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-77563202021-01-07 IPSE, a parasite-derived, host immunomodulatory infiltrin protein, alleviates resiniferatoxin-induced bladder pain Ishida, Kenji Mbanefo, Evaristus C Le, Loc Lamanna, Olivia Pennington, Luke F Finkel, Julia C Jardetzky, Theodore S Falcone, Franco H Hsieh, Michael H Mol Pain Research Article The transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor is an important mediator of nociception and its expression is enriched in nociceptive neurons. TRPV1 signaling has been implicated in bladder pain and is a potential analgesic target. Resiniferatoxin is the most potent known agonist of TRPV1. Acute exposure of the rat bladder to resiniferatoxin has been demonstrated to result in pain-related freezing and licking behaviors that are alleviated by virally encoded IL-4. The interleukin-4-inducing principle of Schistosoma mansoni eggs (IPSE) is a powerful inducer of IL-4 secretion, and is also known to alter host cell transcription through a nuclear localization sequence-based mechanism. We previously reported that IPSE ameliorates ifosfamide-induced bladder pain in an IL-4- and nuclear localization sequence-dependent manner. We hypothesized that pre-administration of IPSE to resiniferatoxin-challenged mice would dampen pain-related behaviors. IPSE indeed lessened resiniferatoxin-triggered freezing behaviors in mice. This was a nuclear localization sequence-dependent phenomenon, since administration of a nuclear localization sequence mutant version of IPSE abrogated IPSE’s analgesic effect. In contrast, IPSE’s analgesic effect did not seem IL-4-dependent, since use of anti-IL-4 antibody in mice given both IPSE and resiniferatoxin did not significantly affect freezing behaviors. RNA-Seq analysis of resiniferatoxin- and IPSE-exposed bladders revealed differential expression of TNF/NF-κb-related signaling pathway genes. In vitro testing of IPSE uptake by urothelial cells and TRPV1-expressing neuronal cells showed uptake by both cell types. Thus, IPSE’s nuclear localization sequence-dependent therapeutic effects on TRPV1-mediated bladder pain may act on TRPV1-expressing neurons and/or may rely upon urothelial mechanisms. SAGE Publications 2020-12-20 /pmc/articles/PMC7756320/ /pubmed/33342372 http://dx.doi.org/10.1177/1744806920970099 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Research Article Ishida, Kenji Mbanefo, Evaristus C Le, Loc Lamanna, Olivia Pennington, Luke F Finkel, Julia C Jardetzky, Theodore S Falcone, Franco H Hsieh, Michael H IPSE, a parasite-derived, host immunomodulatory infiltrin protein, alleviates resiniferatoxin-induced bladder pain |
title | IPSE, a parasite-derived, host immunomodulatory infiltrin protein,
alleviates resiniferatoxin-induced bladder pain |
title_full | IPSE, a parasite-derived, host immunomodulatory infiltrin protein,
alleviates resiniferatoxin-induced bladder pain |
title_fullStr | IPSE, a parasite-derived, host immunomodulatory infiltrin protein,
alleviates resiniferatoxin-induced bladder pain |
title_full_unstemmed | IPSE, a parasite-derived, host immunomodulatory infiltrin protein,
alleviates resiniferatoxin-induced bladder pain |
title_short | IPSE, a parasite-derived, host immunomodulatory infiltrin protein,
alleviates resiniferatoxin-induced bladder pain |
title_sort | ipse, a parasite-derived, host immunomodulatory infiltrin protein,
alleviates resiniferatoxin-induced bladder pain |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756320/ https://www.ncbi.nlm.nih.gov/pubmed/33342372 http://dx.doi.org/10.1177/1744806920970099 |
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