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Papers: 26 Nov 2022 - 2 Dec 2022

2022 Nov 28

J Pathol

EBV infection mediated BDNF expression is associated with bladder inflammation in interstitial cystitis/bladder pain syndrome with Hunner’s lesion.


Jhang J-F, Liu C-D, Hsu Y-H, Chen C-C, Chen H-C, Jiang Y-H, Wu W-C, Peng C-W, Kuo H-C
J Pathol. 2022 Nov 28.
PMID: 36441149.


Interstitial cystitis/bladder pain syndrome with Hunner's lesion (HIC) is characterized by chronic inflammation and nerve hyperplasia; however, the pathogenesis of HIC remains a mystery. In this study, we detected both EBV latency infection genes EBNA-1, LMP-1, and EBV lytic infection BZLF-1 and BRLF-1 expression in the HIC bladders, indicating coexistence of EBV persistence and reactivation in the B cells in HIC bladders. Upregulation of EBV-associated inflammatory genes in the HIC bladders, such as TNF-α and IL-6, suggests EBV infection is implicated in the pathogenesis of bladder inflammation. Nerve hyperplasia and up-regulation of brain-derived neurotrophic factor (BDNF) were noted in the HIC bladders. Double immunochemical staining and flow cytometry revealed the origin of BDNF should be the EBV infected B cells. Inducible BDNF expression was noted in B cells upon EBV infection, but not in the T cells. Chromatin immunoprecipitation study revealed BDNF transcription could be promoted by a cooperation between EBV nuclear antigens, chromatin modifiers, and B cell specific transcription. Knockdown of BDNF in EBV infected B cells resulted in inhibition of cells proliferation and viability. Downregulation of phosphorylated SMAD2 and STAT3 after BDNF knockdown may play a role in the mechanism. Implantation of latent EBV infected B cells into rat bladder walls resulted in higher expression level of CD45 and PGP9.5, suggesting tissue inflammation and nerve hyperplasia. In contrast, implantation of BDNF depleted EBV infected B cells abrogated these effects. This is the first study to provide insights into the mechanisms underlying the involvement of EBV infected B cells in HIC pathogenesis. This article is protected by copyright. All rights reserved.