Abstract
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.
Highlights
Rheumatoid arthritis (RA) is an inflammatory disease that develops between the fourth and seventh decades of life, with a worldwide prevalence of 1%
We conclude that in RA with insulin resistance (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 resolvin E1 (RvE1) levels might not be enough to resolve the inflammation by themselves
Summary
Rheumatoid arthritis (RA) is an inflammatory disease that develops between the fourth and seventh decades of life, with a worldwide prevalence of 1%. In its clinical course the most evident pathological manifestation is joint damage shown by synovitis, progressive degradation of articular cartilage and erosion of the subchondral bone. An early event in the joint damage mechanism is the extravasation of leukocytes to the intra-articular space which is due to the expression of chemokines systems [1, 2]. The early extravasation of leukocytes results in a redundant production of chemokines and pro-inflammatory cytokines that exacerbate the inflammation. This sustained state eventually promotes the characteristic formation of pannus which confirms the established pathological process of RA in the body [5]
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