L&T Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, 41 College Road, Chennai 600006, India; CeNTAB, School of Chemical and Biotechnology, SASTRA University, Tanjore, India.
L&T Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, 41 College Road, Chennai 600006, India.
Mol Cell Neurosci. 2014 Mar;59:10-23. doi: 10.1016/j.mcn.2014.01.001. Epub 2014 Jan 11.
In the retina, increased inflammatory response can cause visual impairment during HIV infection in spite of successful anti-retroviral therapy (HAART). The HIV-1 Tat protein is implicated in neurodegeneration by eliciting a cytokine response in cells of the CNS, including glia. The current study investigated whether innate immune response in human retinal Muller glia could be immune-modulated to combat inflammation. Endocannabinoids, N-arachidonoylethanolamide and 2-arachidonoylglycerol are used to alleviate Tat-induced cytotoxicity and rescue retinal cells. The neuroprotective mechanism involved suppression in production of pro-inflammatory and increase of anti-inflammatory cytokines, mainly through the MAPK pathway. The MAPK regulation was primarily by MKP-1. Both endocannabinoids regulated cytokine production by affecting at the transcriptional level the NF-κB complex, including IRAK1BP1 and TAB2. Stability of cytokine mRNA is likely to have been influenced through tristetraprolin. These findings have direct relevance in conditions like immune-recovery uveitis where anti-retroviral therapy has helped immune reconstitution. In such conditions drugs to combat overwhelming inflammatory response would need to supplement HAART. Endocannabinoids and their agonists may be thought of as neurotherapeutic during certain conditions of HIV-1 induced inflammation.
在视网膜中，尽管抗逆转录病毒疗法（HAART）取得了成功，但炎症反应的增加仍可能导致 HIV 感染期间的视力障碍。HIV-1 Tat 蛋白通过在中枢神经系统的细胞（包括神经胶质细胞）中引发细胞因子反应而与神经退行性变有关。本研究调查了人视网膜 Muller 胶质细胞中的固有免疫反应是否可以通过免疫调节来对抗炎症。内源性大麻素，N-花生四烯酰乙醇胺和 2-花生四烯酰甘油用于减轻 Tat 诱导的细胞毒性并挽救视网膜细胞。神经保护机制涉及抑制促炎细胞因子的产生和抗炎细胞因子的增加，主要通过 MAPK 途径。MAPK 调节主要通过 MKP-1 进行。两种内源性大麻素都通过影响 NF-κB 复合物（包括 IRAK1BP1 和 TAB2）的转录水平来调节细胞因子的产生。细胞因子 mRNA 的稳定性可能通过 tristetraprolin 受到影响。这些发现与免疫重建性葡萄膜炎等情况直接相关，在这种情况下，抗逆转录病毒疗法有助于免疫重建。在这种情况下，需要用对抗过度炎症反应的药物来补充 HAART。内源性大麻素及其激动剂在 HIV-1 诱导的炎症的某些情况下可能被视为神经治疗药物。
