Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain.

<h4>Background</h4>Activation of intravesical protease activated receptor 4 (PAR4) leads to release of urothelial macrophage migration inhibitory factor (MIF). MIF then binds to urothelial MIF receptors to release urothelial high mobility group box-1 (HMGB1) and elicit bladder hyperalges...

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Autores principales:	Shaojing Ye, Fei Ma, Dlovan F D Mahmood, Katherine L Meyer-Siegler, Raymond E Menard, David E Hunt, Lin Leng, Richard Bucala, Pedro L Vera
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7fc27f72d7f44943824ab56be9a0a3f1
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spelling	oai:doaj.org-article:7fc27f72d7f44943824ab56be9a0a3f12021-12-02T20:17:39ZIntravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain.1932-620310.1371/journal.pone.0255975https://doaj.org/article/7fc27f72d7f44943824ab56be9a0a3f12021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0255975https://doaj.org/toc/1932-6203<h4>Background</h4>Activation of intravesical protease activated receptor 4 (PAR4) leads to release of urothelial macrophage migration inhibitory factor (MIF). MIF then binds to urothelial MIF receptors to release urothelial high mobility group box-1 (HMGB1) and elicit bladder hyperalgesia. Since MIF binds to multiple receptors, we investigated the contribution of individual urothelial MIF receptors to PAR4-induced HMGB1 release in vivo and in vitro and bladder pain in vivo.<h4>Methodology/principal findings</h4>We tested the effect of intravesical pre-treatment with individual MIF or MIF receptor (CD74, CXCR4, CXCR2) antagonists on PAR4-induced HMGB1 release in vivo (female C57/BL6 mice) and in vitro (primary human urothelial cells) and on PAR4-induced bladder hyperalgesia in vivo (mice). In mice, PAR4 induced HMGB1 release and bladder hyperalgesia through activation of intravesical MIF receptors, CD74 and CXCR4. CXCR2 was not involved in these effects. In primary urothelial cells, PAR4-induced HMGB1 release through activation of CD74 receptors. Micturition parameters in mice were not changed by any of the treatments.<h4>Conclusions/significance</h4>Urothelial MIF receptors CD74 and CXCR4 mediate bladder pain through release of urothelial HMGB1. This mechanism may set up persistent pain loops in the bladder and warrants further investigation. Urothelial CD74 and CXCR4 may provide novel targets for interrupting bladder pain.Shaojing YeFei MaDlovan F D MahmoodKatherine L Meyer-SieglerRaymond E MenardDavid E HuntLin LengRichard BucalaPedro L VeraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0255975 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shaojing Ye Fei Ma Dlovan F D Mahmood Katherine L Meyer-Siegler Raymond E Menard David E Hunt Lin Leng Richard Bucala Pedro L Vera Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain.
description	<h4>Background</h4>Activation of intravesical protease activated receptor 4 (PAR4) leads to release of urothelial macrophage migration inhibitory factor (MIF). MIF then binds to urothelial MIF receptors to release urothelial high mobility group box-1 (HMGB1) and elicit bladder hyperalgesia. Since MIF binds to multiple receptors, we investigated the contribution of individual urothelial MIF receptors to PAR4-induced HMGB1 release in vivo and in vitro and bladder pain in vivo.<h4>Methodology/principal findings</h4>We tested the effect of intravesical pre-treatment with individual MIF or MIF receptor (CD74, CXCR4, CXCR2) antagonists on PAR4-induced HMGB1 release in vivo (female C57/BL6 mice) and in vitro (primary human urothelial cells) and on PAR4-induced bladder hyperalgesia in vivo (mice). In mice, PAR4 induced HMGB1 release and bladder hyperalgesia through activation of intravesical MIF receptors, CD74 and CXCR4. CXCR2 was not involved in these effects. In primary urothelial cells, PAR4-induced HMGB1 release through activation of CD74 receptors. Micturition parameters in mice were not changed by any of the treatments.<h4>Conclusions/significance</h4>Urothelial MIF receptors CD74 and CXCR4 mediate bladder pain through release of urothelial HMGB1. This mechanism may set up persistent pain loops in the bladder and warrants further investigation. Urothelial CD74 and CXCR4 may provide novel targets for interrupting bladder pain.
format	article
author	Shaojing Ye Fei Ma Dlovan F D Mahmood Katherine L Meyer-Siegler Raymond E Menard David E Hunt Lin Leng Richard Bucala Pedro L Vera
author_facet	Shaojing Ye Fei Ma Dlovan F D Mahmood Katherine L Meyer-Siegler Raymond E Menard David E Hunt Lin Leng Richard Bucala Pedro L Vera
author_sort	Shaojing Ye
title	Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain.
title_short	Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain.
title_full	Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain.
title_fullStr	Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain.
title_full_unstemmed	Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain.
title_sort	intravesical cd74 and cxcr4, macrophage migration inhibitory factor (mif) receptors, mediate bladder pain.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/7fc27f72d7f44943824ab56be9a0a3f1
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Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain.

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