Curcumin alleviates inflammation in Takayasu's arteritis by blocking CCL2 overexpression in adventitial fibroblasts

Takayasu's arteritis (TAK) is a chronic inflammatory disease with several challenges in treatment. Curcumin is known for its anti-inflammatory effects, whereas its effect in the treatment of TAK remains unclear. In this study, we aimed to investigate the effect of curcumin in the treatment of TAK and its underlying mechanisms.16 TAK patients were treated with curcumin granules at a dose of 15 g/day for three months. Kerr score was explored to assess disease activity. Serum levels of inflammatory factors were measured by ELISA. Immunohistochemical and immunofluorescence staining were used to detect the expression of CCL2 (also known as MCP-1) in aortic adventitia. RT-qPCR, ELISA and western blot were used to determine the regulatory effect of curcumin on CCL2 expression in aortic adventitia fibroblasts (AAFs) and its mechanism.Curcumin treatment significantly lowered Kerr score and the levels of serum CCL2 in TAK patients. The expression of CCL2 in TAK aortic adventitia was increased and colocalised with CD68. Serum levels of CCL2 was increased in subjects with Kerr score ≥2. After curcumin treatment, the changes in CCL2 were positively associated with the changes in IL-6. In further analysis, it showed that CCL2 was co-localised with CD90 and α-SMA, markers of adventitia fibroblasts. In vitro, HSP65, an agonist of TLR4, could induce CCL2 expression in AAFs via phosphorylating and activating the JAK2/AKT/STAT3 pathway. Nevertheless, curcumin could reverse the HSP65-induced CCL2 upregulation through restraining JAK2/AKT/STAT3 pathway. The inhibitory effect of curcumin on the JAK2/AKT/STAT3 pathway was even more obvious than that of methotrexate and tofacitinib.Curcumin alleviated inflammation in TAK by downregulating CCL2 overexpression in AAFs through inhibiting the JAK2/AKT/STAT3 signalling pathway.