TNF is a potential therapeutic target to suppress prostatic inflammation and hyperplasia in autoimmune disease.

dc.contributor.author

Vickman, Renee E

dc.contributor.author

Aaron-Brooks, LaTayia

dc.contributor.author

Zhang, Renyuan

dc.contributor.author

Lanman, Nadia A

dc.contributor.author

Lapin, Brittany

dc.contributor.author

Gil, Victoria

dc.contributor.author

Greenberg, Max

dc.contributor.author

Sasaki, Takeshi

dc.contributor.author

Cresswell, Gregory M

dc.contributor.author

Broman, Meaghan M

dc.contributor.author

Paez, J Sebastian

dc.contributor.author

Petkewicz, Jacqueline

dc.contributor.author

Talaty, Pooja

dc.contributor.author

Helfand, Brian T

dc.contributor.author

Glaser, Alexander P

dc.contributor.author

Wang, Chi-Hsiung

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Franco, Omar E

dc.contributor.author

Ratliff, Timothy L

dc.contributor.author

Nastiuk, Kent L

dc.contributor.author

Crawford, Susan E

dc.contributor.author

Hayward, Simon W

dc.date.accessioned

2023-05-03T19:34:40Z

dc.date.available

2023-05-03T19:34:40Z

dc.date.issued

2022-04

dc.date.updated

2023-05-03T19:34:37Z

dc.description.abstract

Autoimmune (AI) diseases can affect many organs; however, the prostate has not been considered to be a primary target of these systemic inflammatory processes. Here, we utilize medical record data, patient samples, and in vivo models to evaluate the impact of inflammation, as seen in AI diseases, on prostate tissue. Human and mouse tissues are used to examine whether systemic targeting of inflammation limits prostatic inflammation and hyperplasia. Evaluation of 112,152 medical records indicates that benign prostatic hyperplasia (BPH) prevalence is significantly higher among patients with AI diseases. Furthermore, treating these patients with tumor necrosis factor (TNF)-antagonists significantly decreases BPH incidence. Single-cell RNA-seq and in vitro assays suggest that macrophage-derived TNF stimulates BPH-derived fibroblast proliferation. TNF blockade significantly reduces epithelial hyperplasia, NFκB activation, and macrophage-mediated inflammation within prostate tissues. Together, these studies show that patients with AI diseases have a heightened susceptibility to BPH and that reducing inflammation with a therapeutic agent can suppress BPH.

dc.identifier

10.1038/s41467-022-29719-1

dc.identifier.issn

2041-1723

dc.identifier.issn

2041-1723

dc.identifier.uri

https://hdl.handle.net/10161/27336

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

dc.relation.ispartof

Nature communications

dc.relation.isversionof

10.1038/s41467-022-29719-1

dc.subject

Cell Line

dc.subject

Animals

dc.subject

Humans

dc.subject

Mice

dc.subject

Prostatic Hyperplasia

dc.subject

Prostatitis

dc.subject

Autoimmune Diseases

dc.subject

Hyperplasia

dc.subject

Inflammation

dc.subject

Male

dc.title

TNF is a potential therapeutic target to suppress prostatic inflammation and hyperplasia in autoimmune disease.

dc.type

Journal article

pubs.begin-page

2133

pubs.issue

1

pubs.organisational-group

Duke

pubs.organisational-group

School of Medicine

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Pathology

pubs.publication-status

Published

pubs.volume

13

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