Curcumin reduces the expression of interleukin 1ß and the production of interleukin 6 and tumor necrosis factor alpha by M1 macrophages from patients with Behcet's disease.

OBJECTIVE: Behcet's disease (BD) is an auto-inflammatory disorder. Curcumin as a bio-active agent has anti-inflammatory properties. Effects of curcumin on the pathogenesis of BD are still not clear. In this study, we investigated the effect of curcumin on the inflammatory cytokines expression and production in M1 macrophages from BD patients compared with healthy controls. METHODS: Monocytes were collected from 10 healthy controls and 20 active BD patients, differentiated to macrophages by macrophage-colony stimulating factor for 7 d. Macrophages were then treated with interferon gamma, lipopolysaccharide, and curcumin (10 or 30 µg/ml) for 24 h. Analysis of tumor necrosis factor-alpha (TNFα), interleukin 1ß (IL-1ß), and IL-6 mRNA expression and protein production was performed using SYBR Green qPCR and ELISA method. RESULTS: Treatment with 30 µg/ml curcumin significantly down-regulated mRNA expression of IL-1ß (p < .05) and protein production of IL-6 (p < .05) in M1 macrophages from BD patients but not in M1 macrophage from controls. Treatment with 30 µg/ml curcumin also significantly diminishes the protein production of TNFα in BD patients (p < .01) and healthy controls (p < .05) M1 macrophages. CONCLUSIONS: We demonstrated that curcumin can inhibit the expression and production of inflammatory cytokines in M1 macrophages from BD patients. Our results suggest that curcumin can modulate inflammatory signaling more specifically in macrophages from BD patients than healthy macrophages.

Macrophages from Behcet's Disease Patients Express Decreased Level of Aryl Hydrocarbon Receptor (AHR) mRNA.

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, connecting environmental stimulators with the immune system. M1 macrophages are a part of immune system that contribute to the inflammatory events in the pathogenesis of Behcet's disease (BD). The effect of AHR on the macrophages in BD patients is still unclear. In this study, we investigated the mRNA expression of AHR in the monocyte-derived and M1 macrophages in active BD patients in comparison to healthy controls. Isolated monocytes from 10 healthy controls and 10 active BD patients were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for 7 days. Cells were then polarized to M1 macrophages by lipopolysaccharide (LPS) and interferon-γ (IFNγ) for 24h. Monocyte purity and macrophage markers expression were analyzed by flow cytometry. Analysis of AHR mRNA expression was performed by SYBR Green real-time PCR. Our results showed that AHR expression is significantly down-regulated in M1 macrophages compare to monocyte-derived macrophages. It was shown that both monocyte-derived macrophages and M1 macrophages from BD patients significantly express lower level of AHR mRNA compared to healthy individuals. Our results demonstrate an anti-inflammatory role for AHR in macrophages, which suggest that decreased AHR expression is associated with pro-inflammatory M1 macrophage and BD susceptibility.