近日,，日本九州大學(xué)副教授津田誠率領(lǐng)的研究小組發(fā)現(xiàn),，導(dǎo)致神經(jīng)病變性疼痛的是一種編號(hào)為IRF8的蛋白質(zhì),。相關(guān)研究報(bào)告發(fā)表在最新一期《細(xì)胞—報(bào)告》（Cell Reports）上。
神經(jīng)病變性疼痛是由于癌癥和糖尿病等原因損傷神經(jīng)而導(dǎo)致的慢性疼痛,，患者非常痛苦,，甚至穿衣服時(shí)輕碰身體，都會(huì)非常疼痛,。
此前的研究表明,，神經(jīng)損傷后腦和脊髓中的小神經(jīng)膠質(zhì)細(xì)胞過度活躍，會(huì)產(chǎn)生使神經(jīng)興奮的物質(zhì),，從而引起疼痛,。但是小神經(jīng)膠質(zhì)細(xì)胞為何會(huì)活躍的機(jī)制卻一直沒弄清,。
津田誠等人在利用小鼠進(jìn)行的實(shí)驗(yàn)中發(fā)現(xiàn),，IRF8蛋白質(zhì)只存在于在小神膠質(zhì)經(jīng)細(xì)胞中,。神經(jīng)損傷后,，小神經(jīng)膠質(zhì)細(xì)胞內(nèi)這種蛋白質(zhì)就會(huì)增加,，處于活躍狀態(tài)，發(fā)揮了激活小神經(jīng)膠質(zhì)細(xì)胞的“開關(guān)”作用,。
全球約有2000萬神經(jīng)病變性疼痛患者，常用嗎啡等麻醉藥鎮(zhèn)痛,，但其效果有限而且會(huì)致人上癮,。津田誠指出：“通過遏制IRF8蛋白質(zhì)的功能,，就有可能緩和慢性疼痛。”研究小組今后準(zhǔn)備繼續(xù)進(jìn)行研究,，爭取發(fā)掘現(xiàn)有藥物遏制IRF8蛋白質(zhì)的功能,。（生物谷Bioon.com）
doi:10.1016/j.celrep.2012.02.014
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IRF8 Is a Critical Transcription Factor for Transforming Microglia into a Reactive Phenotype
Takahiro Masuda, Makoto Tsuda, Ryohei Yoshinaga, Hidetoshi Tozaki-Saitoh, Keiko Ozato, Tomohiko Tamura, Kazuhide Inoue
Microglia become activated by multiple types of damage in the nervous system and play essential roles in neuronal pathologies. However, how microglia transform into reactive phenotypes is poorly understood. Here, we identify the transcription factor interferon regulatory factor 8 (IRF8) as a critical regulator of reactive microglia. Within the spinal cord, IRF8 expression was normally low; however, the expression was markedly upregulated in microglia, but not in neurons or astrocytes, after peripheral nerve injury (PNI). IRF8 overexpression in cultured microglia promoted the transcription of genes associated with reactive states; conversely, IRF8 deficiency prevented these gene expressions in the spinal cord following PNI. Furthermore, IRF8-deficient mice were resistant to neuropathic pain, a common sequela of PNI, and transferring IRF8-overexpressing microglia spinally to normal mice produced pain. Therefore, IRF8 may activate a program of gene expression that transforms microglia into a reactive phenotype. Our findings provide a newly observed mechanism for microglial activation.
