Diaz-Rubio Gustavo Ignacio, Corona-Meraz Fernanda-Isadora, Madrigal-Ruiz Perla-Monserrat, Robles-De Anda Jesús-Aureliano, Gómez-Bañuelos Eduardo, Castro-Albarran Jorge, Flores-Alvarado Luis-Javier, Vázquez-Del Mercado Mónica, Pérez-Vázquez Felipe de Jesús, Pizano-Martínez Oscar-Enrique, Navarro-Hernández Rosa-Elena
Doctorado en Ciencias en Biología Molecular en Medicina, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
UDG-CA-701, Inmunometabolismo en Enfermedades Complejas y Envejecimiento, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
PLoS One. 2021 Jan 28;16(1):e0246054. doi: 10.1371/journal.pone.0246054. eCollection 2021.
Rheumatoid arthritis (RA) has been associated with insulin resistance (IR). Due to an excess in storage of white adipose tissue, IR has an inflammatory process that overlaps with RA. This is performed by the activation/migration of monocytes carried out by the CCR2/CCL2 and CMKLR1/RvE1 chemokines systems. Furthermore, these can potentiate chronic inflammation which is the central axis in the immunopathogenesis of RA. We evaluated the association between the relative expression of CCR2 and CMKLR1 and the serum levels of their ligands CCL2 and RvE1, in the context of adiposity status with IR as a comorbidity in RA. We studied 138 controls and 138 RA-patients classified with and without IR. We evaluated adiposity, RA activity, IR status and immunometabolic profiles by routine methods. Insulin, CCL2 and RvE1 serum levels were determined by ELISA. Relative expression of CCR2, CMKLR1 and RPS28 as constitutive gene by SYBR green RT-qPCR and 2-ΔΔCT method. Increased measurements were observed of body adiposity and metabolic status as follows: RA with IR>control group with IR>RA without IR> control group without IR. CCR2 and CMKLR1 relative expression was increased in RA without IR versus control without IR. CCR2: 2.3- and 1.3-fold increase and CMKLR1: 3.5- and 2.7-fold increase, respectively. Whereas, CCR2 expression correlates with CMKLR1 expression (rho = 0.331) and IR status (rho = 0.497 to 0.548). CMKLR1 expression correlates with inflammation markers (rho = 0.224 to 0.418). CCL2 levels were increased in the RA groups but levels of RvE1 were increased in RA without IR. We conclude that in RA with IR, the chemokine receptors expression pattern showed a parallel increase with their respective ligands. RA and IR in conjunction with the pathological distribution of body fat mass might exacerbate chronic inflammation. These results suggest that high CCL2 levels and compensatory RvE1 levels might not be enough to resolve the inflammation by themselves.
类风湿性关节炎（RA）与胰岛素抵抗（IR）有关。由于白色脂肪组织储存过多，IR存在一个与RA重叠的炎症过程。这是由CCR2/CCL2和CMKLR1/RvE1趋化因子系统介导的单核细胞激活/迁移所导致的。此外，这些趋化因子系统可增强慢性炎症，而慢性炎症是RA免疫发病机制的核心。我们评估了在肥胖状态下，以IR作为RA合并症的情况下，CCR2和CMKLR1的相对表达与其配体CCL2和RvE1血清水平之间的关联。我们研究了138名对照者和138名根据有无IR分类的RA患者。我们通过常规方法评估肥胖、RA活动度、IR状态和免疫代谢谱。通过ELISA测定胰岛素、CCL2和RvE1的血清水平。采用SYBR Green RT-qPCR和2-ΔΔCT法测定CCR2、CMKLR1和作为内参基因的RPS28的相对表达。观察到身体肥胖和代谢状态的测量值增加情况如下：合并IR的RA＞合并IR的对照组＞无IR的RA＞无IR的对照组。与无IR的对照组相比，无IR的RA中CCR2和CMKLR1的相对表达增加。CCR2分别增加2.3倍和1.3倍，CMKLR1分别增加3.5倍和2.7倍。此外，CCR2表达与CMKLR1表达相关（rho = 0.331），与IR状态相关（rho = 0.497至0.548）。CMKLR1表达与炎症标志物相关（rho = 0.224至0.418）。RA组中CCL2水平升高，但无IR的RA中RvE1水平升高。我们得出结论，在合并IR的RA中，趋化因子受体的表达模式与其各自的配体呈平行增加。RA和IR与身体脂肪量的病理分布相结合可能会加剧慢性炎症。这些结果表明，高CCL2水平和代偿性的RvE1水平可能不足以自行解决炎症。
