Association between CCR2 and CCL2 expression and NET stimulation in adult-onset Still’s disease

Abstract

Adult-onset Still’s disease (AOSD) is a systemic inflammatory disease characterized by the activation of monocyte-derived cells and the release of neutrophil extracellular traps (NET). C–C motif ligand (CCL) 2 is a chemoattractant that interacts with the C–C motif chemokine receptor (CCR) 2, resulting in monocyte recruitment and activation. CCL2 and CCR2 were measured with enzyme-linked immunosorbent assay (ELISA) at the serum level, and using immunohistochemical staining at the skin and lymph node tissues levels. THP-1 cell lysates were analyzed using western blot and ELISA after NET stimulation in patients with AOSD. Serum CCL2 level was higher in patients with AOSD than in patients with rheumatoid arthritis and healthy controls (HCs). In patients with AOSD, the percentage of CCL2-positive inflammatory cells in the skin tissues and CCR2-positive inflammatory cells in the lymph nodes increased, compared to that in HCs and in patients with reactive lymphadenopathy, respectively. NET induced in patients with AOSD enhanced the secretion of CCR2, higher CCR2 expression in monocytes, and the levels of interleukin (IL)-1β, IL-6, and IL-18 from THP-1 cells. Our findings suggest that upregulation of the CCL2–CCR2 axis may contribute to the clinical and inflammatory characteristics of AOSD.