Elevated monocyte chemoattractant protein-1 in patients with Behcet's disease

Do, Ju Ho; Jung, Ji Hyun; Park, Chan Seok; Ko, Ji Song; Kim, Soon Sub; Choi, Hyun Cheul; Son, Jang Myung; Min, Do June; Park, Sung Hwan; Cho, Chul Soo; Kim, Ho Youn; Kim, Wan Uk

Abstract

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) belongs to C-C subfamily of chemokines, which stimulates the migration of monocytes. MCP-1 exerts various effects on the monocytes, including the induction of integrin and tissue factor, and synthesis of proinflammatory cytokines and arachidonic acid. In this study, we measured the MCP-1 levels in patients with Behcet's disease and evaluated the associations between the levels of MCP-1 and the level of other chemokines and various clinical features of Behcet's disease.
METHODS
Serum samples were obtained from 67 patients with Behcet's disease and 30 healthy controls. Simultaneously, whole blood was isolated from patients (n=25) with Behcet's disease and healthy controls (n=11) and cultured in 24 well plates for 48 hours in the absence or presence of lipopolysaccharide (LPS) 5 microgram/mL, phytohaemagglutinin (PHA) 5 microgram/mL, phorbol 12-myristate 13-acetate (PMA) 50 ng/mL + ionomycin 5 microgram/mL. The MCP-1 concentrations were measured in the sera and culture supernatants by enzyme-linked immunosorbent assay (ELISA).
RESULTS
The levels of serum MCP-1 were 2.5 times higher in patients with Behcet's disease than healthy controls. The patients with Behcet's disease had also higher levels of MCP-1 in the culture supernatants of whole blood cells, stimulated with LPS, but not with either PHA or PMA plus ionomycin, compared to healthy controls. Serum MCP-1 levels (n=67) were strongly correlated with serum RANTES, MIP-1alpha, IL-8 levels in Behcet's disease. In addition, the production of MCP-1 by whole blood culture from Behcet's disease patients (n=25) were also correlated well with those of RANTES, MIP-1alpha, and IL-8, when stimulated with LPS. However, MCP-1 levels in the sera and culture supernatants did not show any association with various clinical features of Behcet's disease including oral ulcer, genital ulcer, erythema nodosum, arthritis, uveitis, intestinal involvement, central nervous system involvement, and vascular thrombosis.
CONCLUSION
In the sera and culture supernatants of whole blood stimulated with LPS, MCP-1 levels were higher in patients with Behcet's disease than controls and correlated well with RANTES, MIP-1alpha, IL-8 levels. These results suggest that the activation and migration of monocytes triggered by the increased production of MCP-1 may play a role in the pathogenesis of Behcet's disease.