Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ishida, Kenji, Mbanefo, Evaristus C, Le, Loc, Lamanna, Olivia, Pennington, Luke F, Finkel, Julia C, Jardetzky, Theodore S, Falcone, Franco H, Hsieh, Michael H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
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
_version_ 1783626515013959680
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
work_keys_str_mv AT ishidakenji ipseaparasitederivedhostimmunomodulatoryinfiltrinproteinalleviatesresiniferatoxininducedbladderpain
AT mbanefoevaristusc ipseaparasitederivedhostimmunomodulatoryinfiltrinproteinalleviatesresiniferatoxininducedbladderpain
AT leloc ipseaparasitederivedhostimmunomodulatoryinfiltrinproteinalleviatesresiniferatoxininducedbladderpain
AT lamannaolivia ipseaparasitederivedhostimmunomodulatoryinfiltrinproteinalleviatesresiniferatoxininducedbladderpain
AT penningtonlukef ipseaparasitederivedhostimmunomodulatoryinfiltrinproteinalleviatesresiniferatoxininducedbladderpain
AT finkeljuliac ipseaparasitederivedhostimmunomodulatoryinfiltrinproteinalleviatesresiniferatoxininducedbladderpain
AT jardetzkytheodores ipseaparasitederivedhostimmunomodulatoryinfiltrinproteinalleviatesresiniferatoxininducedbladderpain
AT falconefrancoh ipseaparasitederivedhostimmunomodulatoryinfiltrinproteinalleviatesresiniferatoxininducedbladderpain
AT hsiehmichaelh ipseaparasitederivedhostimmunomodulatoryinfiltrinproteinalleviatesresiniferatoxininducedbladderpain