关键词: CB1 receptor CB2 receptor Cannabinoids HTLV‐1‐associated myelopathy/tropical spastic paraparesis Human T-lymphotropic virus 1

Mesh : Humans Male Female Receptor, Cannabinoid, CB1 / metabolism Adult Receptor, Cannabinoid, CB2 / metabolism Paraparesis, Tropical Spastic Middle Aged Human T-lymphotropic virus 1 Gene Products, tax / metabolism Basic-Leucine Zipper Transcription Factors / metabolism Viral Load Retroviridae Proteins / metabolism

来  源:   DOI:10.1016/j.msard.2024.105659

Abstract:
OBJECTIVE: The roles of endocannabinoids are described in immune modulation and neuroprotection. HTLV-1-associated myelopathy (HAM/TSP) is an inflammatory neurodegenerative disease. Therefore, in this study, the interactions of HTLV-1 regulatory factors and host cannabinoid receptors (CBRs) were evaluated in HAM/TSP.
METHODS: Nineteen HAM/TSPs, 22 asymptomatic carriers (ACs), and 18 healthy controls (HCs) were enrolled. RNA was extracted from PBMCs and then reverse-transcribed to cDNA. The gene expression of CB1R and CB2R, as well as HTLV-1 proviral load (PVL), Tax and HTLV-1 basic leucine zipper factor (HBZ) were assessed by RT-qPCR.
RESULTS: The mean expression of CB1R in ACs (8.51 ± 2.76) was significantly higher than HAMTSPs (1.593 ± 0.74, p = 0.05) and also HCs (0.10 ± 0.039, p = 0.001). The CB2R gene expression level in ACs (2.62±0.44) was significantly higher than HAM/TSPs (0.59 ± 0.15, p = 0.001) and HCs (1.00 ± 0.2, p = 0.006). Meanwhile there was a strong correlation between CB1R and CB2R gene expression levels in the HCs and HAM/TSPs (p = 0.001). HTLV-1-Tax expression in HAM/TSPs (386 ± 104) was higher than ACs (75 ± 32) and statistically significant (p = 0.003). While HTLV-1-HBZ was only expressed in three AC subjects and five HAM/TSPs, thus it cannot be analyzed.
CONCLUSIONS: The up-regulation of CB2R has immunomodulatory effects in inflammatory reactions. While CB1R as a neuroprotective agent may suppress inflammatory reactions in ACs, preventing HAM/TSP. It seems that, like multiple sclerosis (MS), cannabinoid medications are beneficial in HAM/TSP.
摘要:
目的:描述了内源性大麻素在免疫调节和神经保护中的作用。HTLV-1相关性脊髓病(HAM/TSP)是一种炎性神经退行性疾病。因此,在这项研究中,在HAM/TSP中评估了HTLV-1调节因子与宿主大麻素受体(CBRs)的相互作用。
方法:19个HAM/TSP,22名无症状携带者(AC),并纳入18名健康对照(HCs)。从PBMC中提取RNA,然后逆转录为cDNA。CB1R和CB2R的基因表达,以及HTLV-1前病毒负荷(PVL),通过RT-qPCR评估Tax和HTLV-1碱性亮氨酸拉链因子(HBZ)。
结果:CB1R在ACs中的平均表达(8.51±2.76)显着高于HAMTSP(1.593±0.74,p=0.05)和HCs(0.10±0.039,p=0.001)。ACs中CB2R基因表达水平(2.62±0.44)显著高于HAM/TSPs(0.59±0.15,p=0.001)和HCs(1.00±0.2,p=0.006)。同时,HCs和HAM/TSP中CB1R和CB2R基因表达水平之间存在很强的相关性(p=0.001)。HAM/TSP中的HTLV-1-Tax表达(386±104)高于AC(75±32),具有统计学意义(p=0.003)。虽然HTLV-1-HBZ仅在三个AC受试者和五个HAM/TSP中表达,因此无法分析。
结论:CB2R的上调在炎症反应中具有免疫调节作用。虽然CB1R作为神经保护剂可以抑制ACs的炎症反应,防止HAM/TSP。看来,像多发性硬化症(MS),大麻素药物对HAM/TSP有益。
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