title: Interleukin-driven insulin-like growth factor promotes prostatic inflammatory hyperplasia.
abstract: Prostatic inflammation is of considerable importance to urologic research because of its association with benign prostatic hyperplasia and prostate cancer. However, the mechanisms by which inflammation leads to proliferation and growth remain obscure. Here, we show that insulin-like growth factors (IGFs), previously known as critical developmental growth factors during prostate organogenesis, are induced by inflammation as part of the proliferative recovery to inflammation. Using genetic models and in vivo IGF receptor blockade, we demonstrate that the hyperplastic response to inflammation depends on interleukin-1-driven IGF signaling. We show that human prostatic hyperplasia is associated with IGF pathway activation specifically localized to foci of inflammation. This demonstrates that mechanisms of inflammation-induced epithelial proliferation and hyperplasia involve the induction of developmental growth factors, further establishing a link between inflammatory and developmental signals and providing a mechanistic basis for the management of proliferative diseases by IGF pathway modulation.
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana (A.M.H., J.D.M., T.J.J.); Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin (E.K.M., S.L.); and Melvin and Bren Simon Cancer Center, Indiana Basic Urological Research Working Group, Indiana University, Indianapolis, Indiana (T.J.J.).
authors.forename: Alana M
authors.initials: AM
authors.lastname: Hahn
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana (A.M.H., J.D.M., T.J.J.); Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin (E.K.M., S.L.); and Melvin and Bren Simon Cancer Center, Indiana Basic Urological Research Working Group, Indiana University, Indianapolis, Indiana (T.J.J.).
authors.forename: Jason D
authors.initials: JD
authors.lastname: Myers
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana (A.M.H., J.D.M., T.J.J.); Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin (E.K.M., S.L.); and Melvin and Bren Simon Cancer Center, Indiana Basic Urological Research Working Group, Indiana University, Indianapolis, Indiana (T.J.J.).
authors.forename: Eliza K
authors.initials: EK
authors.lastname: McFarland
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana (A.M.H., J.D.M., T.J.J.); Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin (E.K.M., S.L.); and Melvin and Bren Simon Cancer Center, Indiana Basic Urological Research Working Group, Indiana University, Indianapolis, Indiana (T.J.J.).
authors.forename: Sanghee
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana (A.M.H., J.D.M., T.J.J.); Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin (E.K.M., S.L.); and Melvin and Bren Simon Cancer Center, Indiana Basic Urological Research Working Group, Indiana University, Indianapolis, Indiana (T.J.J.) ttjerde@iupui.edu.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Jerde
mesh_terms: D000368:Aged; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D007375:Interleukin-1 / Q000172:deficiency*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000139:chemically induced / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013002:Somatomedins / Q000096:biosynthesis* / Q000633:toxicity
chemical_list: D007375:Interleukin-1; D013002:Somatomedins