Penna Giuseppe, Fibbi Benedetta, Amuchastegui Susana, Cossetti Chiara, Aquilano Francesca, Laverny Gilles, Gacci Mauro, Crescioli Clara, Maggi Mario, Adorini Luciano
BioXell, Milan, Italy.
J Immunol. 2009 Apr 1;182(7):4056-64. doi: 10.4049/jimmunol.0801875.
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-gamma 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.
良性前列腺增生（BPH）是一种高度常见的前列腺疾病，其发病机制可能涉及炎症成分。在本研究中，我们发现从BPH组织获得的人前列腺基质细胞可通过分泌促炎细胞因子以及能够募集淋巴细胞和单核细胞的趋化因子，并作为抗原呈递细胞（APC），积极参与炎症过程。BPH细胞表达所有的Toll样受体（TLR），其连接可导致CXCL8/IL-8、CXCL10和IL-6的分泌。此外，BPH细胞表达共刺激分子以及I类和II类主要组织相容性复合体（MHC）分子，这些分子可激活同种异体反应性CD4(+)细胞，进而显著上调BPH细胞分泌IL-12/IL-23p40和IL-12p75。被BPH细胞激活的同种异体反应性CD4(+)细胞分泌干扰素-γ（IFN-γ）和白细胞介素-17（IL-17）。这些细胞因子上调BPH细胞产生IL-6、IL-8和CXCL10，形成一个可放大炎症的正反馈回路。IL-8诱导BPH细胞的自分泌/旁分泌增殖，这也表明该趋化因子在疾病发病机制中具有促进生长的活性。这些结果表明，人BPH细胞代表能够诱导和维持慢性炎症过程的非专职APC，支持炎症在BPH发病机制中的相关性。
