Interleukin-1 Induced Epithelial Proliferation in Prostate Development and Hyperplasia Is Mediated by Stromal Insulin-Like Growth Factor-1 Induction

Expansion of prostate epithelial progenitor cells after inflammation of the mouse prostate

“…Previous work from our laboratory has demonstrated that development of the prostate requires activation of IL-1-driven IGF signaling and that this event is recapitulated during the induction of prostatic inflammation (11,16). Inflammation is associated with many developmental-like features as part of the repair and recovery process, and the present study demonstrates that expansion of tissue progenitor cells is yet another process of developmental biology that is reactivated by inflammation.…”

“…All animal experiments were conducted under the approval and supervision of the Animal Care and Use Committee of the Indiana University School of Medicine and in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Esherichia coli strain 1677 (2 ϫ 10 6 bacteria/ml, 100 l/mouse) was instilled through catheters into the urinary tract of C57BL/6J wild-type (WT) and IL-1R1 Ϫ/Ϫ mice (The Jackson Laboratory, Bar Harbor, ME; verified by genotyping) at 8 wk of age as previously described (2,16). Mice were inoculated with 100 g of bromodeoxyuridine (BrdU; Roche) 2 h before euthanization, and groups were euthanized daily 1-7 days after bacterial induction.…”

“…The finding that progenitor cell expansion is reduced by Ͼ50% in IL-1R1 Ϫ/Ϫ mice relative to C57BL/6J control mice indicates that IL-1R signaling plays a role in inflammation-induced progenitor cell expansion. Of note, IL-1R-null mice still mount an effective inflammatory reaction complete with neutrophils, lymphocytes, and macrophages (16), so the effect of IL-1R on hyperplasia resulting from inflammation appears to be at the epithelial-stromal interaction level rather than in reducing inflammation. It must also be noted, however, that this was not a complete abrogation; therefore, other cytokines and growth factors are likely involved in this process.…”

“…These four-marker cells express Sca-1, CD44, CD133, and c-Kit (CD117). Since we have already shown that IL-1 receptor 1 (IL-1R1) signaling is essential for both prostate development and inflammationinduced epithelial cells (16,11), we also postulated that progenitor cell expansion by inflammation is IL-1 signaling dependent.…”

“…We have previously shown that activation of signaling pathways shared by inflammation and organ development is necessary for inflammation-induced prostate epithelial hyperplasia (16). The similarities between tissue development and adult tissue regeneration suggested a critical role of pluripotent cells in inflammation-induced tissue repair.…”