Department of Urology and Division of Rheumatology, Northwestern University, Chicago, Illinois 60611, USA.
J Urol. 2010 Oct;184(4):1536-42. doi: 10.1016/j.juro.2010.05.086. Epub 2010 Aug 17.
In the past numerous chemokines have been noted in the expressed prostatic secretions of patients with chronic prostatitis/chronic pelvic pain syndrome. We examined the functional effects of chemokines in expressed prostatic secretions of patients with chronic pelvic pain syndrome.
We studied the functional effects of expressed prostatic secretions on human monocytes by examining monocyte chemotaxis in response to monocyte chemoattractant protein-1, a major chemoattractant previously identified in chronic prostatitis/chronic pelvic pain syndrome cases. We determined effects on cellular signaling by quantifying intracellular calcium increase in monocytes and nuclear factor-κB activation in normal prostate epithelial cells.
Results show that the monocyte chemoattractant protein-1 in expressed prostatic secretions is nonfunctional with an inability to mediate human monocyte chemotaxis, or mediate signaling in monocytes or prostate epithelial cells. This lack of functionality could be extended to other proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α, when incubated with expressed prostatic secretions from patients with chronic pelvic pain syndrome. The mechanism underlying this apparent ability to modulate proinflammatory cytokines involves heat labile extracellular proteases that mediate the inhibition of immune and prostate epithelial cell function.
These results may have implications for the design of specific diagnostic and therapeutic methods targeted toward the complete resolution of prostate inflammatory insults.
在过去,许多趋化因子已在慢性前列腺炎/慢性骨盆疼痛综合征患者的前列腺分泌物中被发现。我们研究了趋化因子在慢性骨盆疼痛综合征患者前列腺分泌物中的功能效应。
我们通过检测单核细胞趋化蛋白-1(先前在慢性前列腺炎/慢性骨盆疼痛综合征病例中鉴定的主要趋化因子)对人单核细胞的趋化作用,研究了前列腺分泌物对人单核细胞的功能效应。我们通过定量检测单核细胞内钙离子增加和正常前列腺上皮细胞中核因子-κB 的激活,来确定细胞信号转导的影响。
结果表明,前列腺分泌物中的单核细胞趋化蛋白-1无功能,无法介导人单核细胞趋化,或介导单核细胞或前列腺上皮细胞的信号转导。当与慢性骨盆疼痛综合征患者的前列腺分泌物孵育时,这种无功能性可能扩展到其他促炎细胞因子,如白细胞介素-1β和肿瘤坏死因子-α。这种调节促炎细胞因子的能力的机制涉及热不稳定的细胞外蛋白酶,它介导免疫和前列腺上皮细胞功能的抑制。
这些结果可能对设计针对前列腺炎症刺激的完全缓解的特定诊断和治疗方法具有重要意义。