Ferret-Sena Véronique, Maia E Silva Alexandra, Sena Armando, Cavaleiro Inês, Vale José, Derudas Bruno, Chinetti-Gbaguidi Giulia, Staels Bart
Interdisciplinary Centre of Research Egas Moniz (CiiEM), Caparica, Portugal.
Interdisciplinary Centre of Research Egas Moniz (CiiEM), Caparica, Portugal; Neurology Service, Hospital dos Capuchos, Centro Hospitalar Lisboa Central, Lisboa, Portugal.
PPAR Res. 2016;2016:5716415. doi: 10.1155/2016/5716415. Epub 2016 Dec 18.
Peroxisome Proliferator-Activated Receptors (PPAR) are transcription factors suggested to be involved in inflammatory lesions of autoimmune encephalomyelitis and multiple sclerosis (MS). Our objective was to assess whether Natalizumab (NTZ) therapy is associated with alterations of PPAR expression in MS patients. We analyzed gene expression of PPAR in peripheral blood mononuclear cells (PBMC) as well as blood inflammatory markers in women with MS previously medicated with first-line immunomodulators (baseline) and after NTZ therapy. No differences in PPAR, PPAR/, PPAR, and CD36 mRNA expression were found in PBMC between patients under baseline and healthy controls. At three months, NTZ increased PPAR/ mRNA ( = 0.009) in comparison to baseline, while mRNA expression of PPAR and CD36 (a well-known PPAR target gene) was lower in comparison to healthy controls ( = 0.026 and = 0.028, resp.). Although these trends of alterations remain after six months of therapy, the results were not statistically significant. Osteopontin levels were elevated in patients ( = 0.002) and did not change during the follow-up period of NTZ treatment. These results suggest that PPAR-mediated processes may contribute to the mechanisms of action of NTZ therapy.
过氧化物酶体增殖物激活受体（PPAR）是一类转录因子，被认为与自身免疫性脑脊髓炎和多发性硬化症（MS）的炎症性病变有关。我们的目的是评估那他珠单抗（NTZ）治疗是否与MS患者PPAR表达的改变有关。我们分析了既往接受一线免疫调节剂治疗（基线）的MS女性患者以及接受NTZ治疗后的外周血单个核细胞（PBMC）中PPAR的基因表达以及血液炎症标志物。在基线患者和健康对照之间，PBMC中PPAR、PPAR/、PPAR和CD36 mRNA表达未发现差异。在三个月时，与基线相比，NTZ使PPAR/ mRNA升高（P = 0.009），而与健康对照相比，PPAR和CD36（一个众所周知的PPAR靶基因）的mRNA表达较低（分别为P = 0.026和P = 0.028）。尽管在治疗六个月后这些改变趋势仍然存在，但结果无统计学意义。患者骨桥蛋白水平升高（P = 0.002），在NTZ治疗的随访期间未发生变化。这些结果表明，PPAR介导的过程可能有助于NTZ治疗的作用机制。
