Expansion of prostate epithelial progenitor cells after inflammation of the mouse prostate.
Prostatic inflammation is a nearly ubiquitous pathological feature observed in specimens from benign prostate hyperplasia and prostate cancer patients. The microenvironment of the inflamed prostate is highly reactive, and epithelial hyperplasia is a hallmark feature of inflamed prostates. How inflammation orchestrates epithelial proliferation as part of its repair and recovery action is not well understood. Here, we report that a novel epithelial progenitor cell population is induced to expand during inflammation. We used sphere culture assays, immunofluorescence, and flow cytometry to show that this population is increased in bacterially induced inflamed mouse prostates relative to naïve control prostates. We confirmed from previous reports that this population exclusively possesses the ability to regrow entire prostatic structures from single cell culture using renal grafts. In addition, putative progenitor cells harvested from inflamed animals have greater aggregation capacity than those isolated from naïve control prostates. Expansion of this critical cell population requires IL-1 signaling, as IL-1 receptor 1-null mice exhibit inflammation similar to wild-type inflamed animals but exhibit significantly reduced progenitor cell proliferation and hyperplasia. These data demonstrate that inflammation promotes hyperplasia in the mouse prostatic epithelium by inducing the expansion of a selected epithelial progenitor cell population in an IL-1 receptor-dependent manner. These findings may have significant impact on our understanding of how inflammation promotes proliferative diseases such as benign prostatic hyperplasia and prostate cancer, both of which depend on expansion of cells that exhibit a progenitor-like nature.
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana; Melvin and Bren Simon Cancer Center-Indiana Basic Urological Research Working Group, Indiana University, Indianapolis, Indiana.
Liang
L
Wang
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana;
Marloes
M
Zoetemelk
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana;
Brahmananda R
BR
Chitteti
Department of Comparative Pathobiology, Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana; Melvin and Bren Simon Cancer Center-Indiana Basic Urological Research Working Group, Indiana University, Indianapolis, Indiana.
Timothy L
TL
Ratliff
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana;
Jason D
JD
Myers
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; and Melvin and Bren Simon Cancer Center-Indiana Basic Urological Research Working Group, Indiana University, Indianapolis, Indiana.
Edward F
EF
Srour
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; and Melvin and Bren Simon Cancer Center-Indiana Basic Urological Research Working Group, Indiana University, Indianapolis, Indiana.
Hal
H
Broxmeyer
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana; Melvin and Bren Simon Cancer Center-Indiana Basic Urological Research Working Group, Indiana University, Indianapolis, Indiana tjjerde@iupui.edu.
Travis J
TJ
Jerde
D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000473:pathology; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011470:Prostatic Hyperplasia / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology*
D007375:Interleukin-1
hyperplasia; inflammation; interleukin-1; progenitor; prostate