Pérez-Martínez Pamela I, Rojas-Espinosa Oscar, Hernández-Chávez Víctor G, Arce-Paredes Patricia, Estrada-Parra Sergio
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.
Departamento de Morfología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.
Int J Exp Pathol. 2020 Feb;101(1-2):55-64. doi: 10.1111/iep.12348. Epub 2020 May 27.
Rheumatoid arthritis is a disabling autoimmune disease with a high global prevalence. Treatment with disease-modifying anti-arthritic drugs (DIMARDs) has been routinely used with beneficial effects but with adverse long-term consequences; novel targeted biologics and small-molecule inhibitors are promising options. In this study, we investigated whether purified omega unsaturated fatty acids (ω-UFAs) and dialysable leukocyte extracts (DLEs) prevented the development of arthritis in a model of collagen-induced arthritis (CIA) in mice. We also investigated whether the transcription factor NF-κB and the NLRP3 inflammasome were involved in the process and whether their activity was modulated by treatment. The development of arthritis was evaluated for 84 days following treatment with nothing, dexamethasone, DLEs, docosahexaenoic acid, arachidonic acid, and oleic acid. Progression of CIA was monitored by evaluating clinical manifestations, inflammatory changes, and histological alterations in the pads' articular tissues. Both DLEs and ω-UFAs led to an almost complete inhibition of the inflammatory histopathology of CIA and this was concomitant with the inhibition of NF-kB and the inhibition of the activation of NLRP3. These data suggest that ω-UFAs and DLEs might have NF-κB as a common target and that they might be used as ancillary medicines in the treatment of arthritis.
类风湿性关节炎是一种致残性自身免疫疾病,在全球范围内具有较高的患病率。使用改善病情的抗风湿药物(DMARDs)进行治疗一直是常规做法,虽有有益效果,但存在长期不良后果;新型靶向生物制剂和小分子抑制剂是很有前景的选择。在本研究中,我们调查了纯化的ω-不饱和脂肪酸(ω-UFAs)和可透析白细胞提取物(DLEs)是否能在小鼠胶原诱导性关节炎(CIA)模型中预防关节炎的发展。我们还研究了转录因子NF-κB和NLRP3炎性小体是否参与该过程,以及它们的活性是否受到治疗的调节。在用空白对照、地塞米松、DLEs、二十二碳六烯酸、花生四烯酸和油酸处理后,对关节炎的发展进行了84天的评估。通过评估爪部关节组织的临床表现、炎症变化和组织学改变来监测CIA的进展。DLEs和ω-UFAs均导致CIA炎性组织病理学几乎完全受到抑制,这与NF-κB的抑制以及NLRP3激活的抑制相伴发生。这些数据表明,ω-UFAs和DLEs可能以NF-κB作为共同靶点,并且它们可能用作关节炎治疗的辅助药物。