IL-17A causes depression-like symptoms via NFκB and p38MAPK signaling pathways in mice: Implications for psoriasis associated depression
IL-17A causes depression-like symptoms via NFκB and p38MAPK signaling pathways in mice: Implications for psoriasis associated depression
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DOI：
10.1016/j.cyto.2017.05.018
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发表时间：
2017-09-01
期刊：
影响因子：
3.8
通讯作者：
Attia, Sabry M.
中科院分区：
文献类型：
--
作者：
Nadeem, Ahmed;Ahmad, Sheikh F.;Attia, Sabry M.
研究表明，银屑病与合并重度抑郁症的患病率增加有关。IL-17 A在抑郁症和银屑病中起重要作用。IL-17 A已显示在银屑病患者的体循环中升高。银屑病期间从不同免疫细胞释放的IL-17 A可能是与抑郁症相关的神经精神症状发展的原因。因此，本研究探讨了系统性IL-17 A与抑郁症的关系。本研究利用咪喹莫特银屑病炎症模型以及IL-17 A给药小鼠来研究IL-17 A对抑郁样行为的影响。银屑病炎症导致先天性和适应性来源的外周免疫细胞中IL-17 A表达增强。这与不同脑区NF κ B B/p38 MAPK信号传导和炎症介质的增加以及抑郁样症状（如蔗糖偏好和悬尾试验所反映的）有关。IL-17 A的作用通过单独给药10天，然后评估相同的参数来进一步证实。IL-17 A给药对神经行为和NF κ B/p38 MAPK通路产生了与银屑病样炎症相似的作用。此外，NF κ B和p38 MAPK抑制剂均通过减少炎症介质（如MCP-1、iNOS、IL-6和CXCL-2）导致与抑郁样行为相关的IL-17 A减弱。此外，抗IL 17 A抗体还导致咪喹莫特诱导的抑郁样症状以及NF κ B/p38 MAPK信号传导的减少。目前的研究表明，IL-17 A在与银屑病炎症相关的共病抑郁症中起重要作用，其中NF κ B和p38 MAPK通路通过上调脑中的炎症介质起重要作用。
Psoriasis has been shown to be associated with an increased prevalence of comorbid major depression. IL-17A plays an important role in both depression and psoriasis. IL-17A has been shown to be elevated in systemic circulation of psoriatic patients. IL-17A released from different immune cells during psoriasis may be responsible for the development of neuropsychiatric symptoms associated with depression. Therefore, this study explored the association of systemic IL-17A with depression. The present study utilized imiquimod model of psoriatic inflammation as well as IL-17A administration in mice to investigate the effect of IL-17A on depression-like behavior. Psoriatic inflammation led to enhanced IL-17A expression in peripheral immune cells of both innate and adaptive origin. This was associated with increased NF kappa B/p38MAPK signaling and inflammatory mediators in different brain regions, and depression-like symptoms (as reflected by sucrose preference and tail suspension tests). The role of IL-17A was further confirmed by administering it alone for ten days, followed by assessment of the same parameters. IL-17A administration produced effects similar to psoriasis-like inflammation on neurobehavior and NF kappa B/p38MAPK pathways. Moreover, both NF kappa B and p38MAPK inhibitors led to attenuation in IL-17A associated with depression-like behavior via reduction in inflammatory mediators, such as MCP-1, iNOS, IL-6, and CXCL-2. Furthermore, anti-IL17A antibody also led to a reduction in imiquimod-induced depression-like symptoms, as well as NF kappa B/p38MAPK signaling. The present study shows that IL-17A plays an important role in comorbid depression associated with psoriatic inflammation, where both NF kappa B and p38MAPK pathways play significant roles via upregulation of inflammatory mediators in the brain.