Pereira Ione, Mendes Saulo J F, Pereira Domingos M S, Muniz Thayanne F, Colares Valderlane L P, Monteiro Cinara R A V, Martins Mahiba M R de S, Grisotto Marcos A G, Monteiro-Neto Valério, Monteiro Sílvio G, Calixto João B, Brain Susan D, Fernandes Elizabeth S
Programa de Pós-graduação, Universidade Ceuma, São Luís MA, Brazil.
Programa de Pós-graduação, Universidade Ceuma, São LuísMA, Brazil; Programa de Pós-graduação, Universidade Federal do Maranhão, São LuísMA, Brazil.
Front Pharmacol. 2017 Feb 10;8:53. doi: 10.3389/fphar.2017.00053. eCollection 2017.
Patients with rheumatoid arthritis (RA) suffer from pain and joint disability. The transient receptor potential ankyrin 1 (TRPA1) channel expressed on sensory neurones and non-neuronal cells mediates pain transduction and inflammation and it has been implicated in RA. However, there is little information on the contribution of TRPA1 for human disease. Here, we investigated the expression of TRPA1 on peripheral blood leukocytes and the circulating levels of its endogenous activators 4-hydroxynonenal (4-HNE) and hydrogen peroxide (HO) in RA patients treated or not with the anti-rheumatic leflunomide (LFN) or the anti-TNFα adalimumab (ADA). We also assessed whether TRPA1 expression correlates with joint pain and disability, in addition to the immune changes in RA. TRPA1 expression on peripheral blood leukocytes correlated with pain severity and disability. TRPA1 levels on these cells were associated with the numbers of polymorphonuclear and the activation of CD14 cells. No correlations were found between the lymphocyte population and TRPA1 expression, pain or disability. Patients recently diagnosed with RA expressed increased levels of TRPA1 on their leukocytes whilst treatment with either LFN or ADA down-regulated this receptor probably by reducing the numbers of polymorphonuclears and the activation of CD14 cells. We suggest that the activation levels of CD14 cells, the numbers of PMNs in the peripheral blood and the expression of TRPA1 on peripheral blood leukocytes correlate with RA progression, affecting joint pain sensitivity and loss of function.
类风湿关节炎（RA）患者饱受疼痛和关节残疾之苦。感觉神经元和非神经元细胞上表达的瞬时受体电位锚蛋白1（TRPA1）通道介导疼痛传导和炎症，并且与RA有关。然而，关于TRPA1对人类疾病的作用，相关信息甚少。在此，我们研究了接受或未接受抗风湿药物来氟米特（LFN）或抗TNFα药物阿达木单抗（ADA）治疗的RA患者外周血白细胞上TRPA1的表达及其内源性激活剂4-羟基壬烯醛（4-HNE）和过氧化氢（HO）的循环水平。除了RA中的免疫变化外，我们还评估了TRPA1表达是否与关节疼痛和残疾相关。外周血白细胞上的TRPA1表达与疼痛严重程度和残疾相关。这些细胞上的TRPA1水平与多形核细胞数量和CD14细胞的激活有关。未发现淋巴细胞群体与TRPA1表达、疼痛或残疾之间存在相关性。最近诊断为RA的患者白细胞上TRPA1表达水平升高，而使用LFN或ADA治疗可能通过减少多形核细胞数量和CD14细胞的激活来下调该受体。我们认为CD14细胞的激活水平、外周血中多形核白细胞的数量以及外周血白细胞上TRPA1的表达与RA进展相关，影响关节疼痛敏感性和功能丧失。
