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Human Benign Prostatic Hyperplasia Stromal Cells As Inducers and Targets of Chronic Immuno-Mediated Inflammation¹

Giuseppe Penna^*, Benedetta Fibbi, Susana Amuchastegui^*, Chiara Cossetti^*, Francesca Aquilano^*, Gilles Laverny^*, Mauro Gacci, Clara Crescioli, Mario Maggi and Luciano Adorini^2,*

^* BioXell, Milan, Italy; and Andrology Unit, Department of Clinical Physiopathology and Department of Urology, University of Florence, Italy

Benign prostatic hyperplasia (BPH), a highly prevalent prostatic condition, could involve an inflammatory component in disease pathogenesis. In this study, we show that human stromal prostate cells obtained from BPH tissue can actively contribute to the inflammatory process by secreting proinflammatory cytokines as well as chemokines able to recruit lymphomonuclear cells and by acting as APCs. BPH cells express all of the TLRs and their ligation leads to the secretion of CXCL8/IL-8, CXCL10, and IL-6. In addition, BPH cells express costimulatory as well as class I and class II MHC molecules, which activate alloreactive CD4⁺ cells that in turn markedly up-regulate IL-12/IL-23p40 and IL-12p75 secretion by BPH cells. Alloreactive CD4⁺ cells activated by BPH cells secrete IFN- and IL-17. These cytokines up-regulate IL-6, IL-8, and CXCL10 production by BPH cells, creating a positive feedback loop that can amplify inflammation. IL-8 induces autocrine/paracrine proliferation of BPH cells, indicating also a growth-promoting activity of this chemokine in disease pathogenesis. These results show that human BPH cells represent nonprofessional APCs able to induce and sustain chronic inflammatory processes, supporting the relevance of inflammation in BPH pathogenesis.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by European Community Grant NucSys (to L.A.).

² Address correspondence and reprint requests to Dr. Luciano Adorini at the current address: Intercept Pharma, Via P. Togliatti 22 bis, 06073 Corciano (Perugia), Italy. E-mail address: LAdorini{at}interceptpharma.com

³ Abbreviations used in this paper: BPH, benign prostatic hyperplasia; CP/CPPS, chronic prostatitis/chronic pelvic pain syndrome; TURP, transurethral resection of the prostate; KGF, keratinocyte growth factor; IGF, insulin growth factor.