Experimental autoimmune prostatitis induces microglial activation in the spinal cord.
Experimental autoimmune prostatitis induces microglial activation in the spinal cord.
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DOI：
10.1002/pros.22891
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发表时间：
2015-01
期刊：
影响因子：
2.8
通讯作者：
Thumbikat, Praveen
中科院分区：
文献类型：
--
作者：
Wong, Larry;Done, Joseph D.;Schaeffer, Anthony J.;Thumbikat, Praveen
慢性前列腺炎/慢性盆腔疼痛综合征的发病机制尚不清楚，包括宿主免疫反应和神经系统在内的因素已被归因于CP/CPPS的发展。我们先前证明肥大细胞和趋化因子如CCL 2和CCL 3在介导前列腺炎中起重要作用。在此，我们研究了中枢神经系统中的神经炎症和小胶质细胞在慢性盆腔疼痛发展中的作用。用大鼠前列腺抗原皮下注射诱发实验性自身免疫性前列腺炎（EAP）。分离骶脊髓组织（S4-S5段）并用于免疫荧光或QRT-PCR分析。触觉异常性疼痛在基线和EAP过程中的不同时间点使用Von Frey纤维作为骨盆疼痛的函数进行测量。EAP小鼠在前列腺炎30天后用米诺环素治疗，以测试小胶质细胞抑制对骨盆疼痛的功效。前列腺炎诱导脊髓中小胶质细胞的扩增和活化以及炎症的发展，这通过增加CCL 3、IL-1β、Iba 1和ERK 1/2磷酸化的表达水平来确定。前列腺炎小鼠的小胶质细胞活化导致P2 X4 R表达增加和BDNF水平升高，这是两种与慢性疼痛相关的分子标志物。药理学抑制小胶质细胞可减轻前列腺炎小鼠的疼痛，并导致IL-1β、P2 X4 R和BDNF表达减少。我们的数据表明，前列腺炎导致脊髓炎症和小胶质细胞的激活和扩张，这些机制可能有助于慢性盆腔疼痛的发展和维持。
The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host’s immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S4–S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain. Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF. Our data shows that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain.
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LY6C+“炎症单核细胞”是在西尼罗河病毒脑炎中以致病方式募集的小胶质前体。
DOI：
10.1084/jem.20080421
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Getts DR;Terry RL;Getts MT;Müller M;Rana S;Shrestha B;Radford J;Van Rooijen N;Campbell IL;King NJ
通讯作者：
King NJ
影响因子：
7.4
作者：
Piao, ZG;Cho, IH;Oh, SB
通讯作者：
Oh, SB
影响因子：
2.8
作者：
Knerlich-Lukoschus, Friederike;von der Ropp-Brenner, Beata;Held-Feindt, Janka
通讯作者：
Held-Feindt, Janka
影响因子：
3.3
作者：
Menetski, J.;Mistry, S.;Abbadie, C.
通讯作者：
Abbadie, C.
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG