Interleukin-17A enhances the production of CD147/extracellular matrix metalloproteinase inducer by monocytes from patients with psoriasis.

Abstract

CD147 is the main inducer of extracellular matrix metalloproteinases, which are critically involved in different inflammatory diseases. Our objective was to assess whether in vitro stimulation with Th1 and Th17 cytokines modulate CD147 production in monocytes from psoriasis patients. Serum CD147 levels were measured in 60 psoriasis patients and 60 healthy controls. Furthermore, CD14+ monocytes were cultured and stimulated with TNF, IFN-g or IL-17A, and CD147 production was measured. Serum CD147 levels were higher in psoriasis patients (median 1866, IQR 1517-2355 pg/mL vs. 1686, 1382-1947 pg/mL; p=0.023), allowing to distinguish between patients and controls (AUC-ROC 0.632 ± 0.0509). Baseline CD147 production was similar in monocytes from patients and controls (1298, 769-1645 pg/mL vs. 1290, 1048-1976 pg/ml, respectively). Stimulation with IL-17A (1638, 1426-2027 pg/mL; p<0.001), but no other cytokine, was associated with increased production of CD147 in monocytes from psoriatic patients. In contrast, none of the cytokines increased CD147 production in monocytes from healthy controls. CD147 production by activated monocytes is a cytokine-dependent process, specifically by cytokines of the Th17 phenotype instead of those belonging to the Th1 phenotype. CD147 is a novel inflammatory mediator that could be a therapeutic target in psoriasis.