Regulation of disease susceptibility and mononuclear cell infiltration into the labial salivary glands of Sjögren's syndrome by monocyte chemotactic protein-1.

Abstract

To investigate how monocyte chemotactic protein-1 (MCP-1) is involved in the pathological process of primary SS (pSS). Guanine (G) to adenine (A) single nucleotide polymorphism (SNP) of the -2518 MCP-1 promoter region in pSS and healthy controls was determined by the PCR-restriction fragment length polymorphism technique. Immunohistochemical staining towards MCP-1 and C-C motif chemokine receptor-2 (CCR2), a receptor of MCP-1, of the labial salivary glands of pSS was investigated. Furthermore, the expression of MCP-1 and CCR2 from the cultured primary salivary epithelial cells was studied by RT-PCR, ELISA and western blotting. The genotype and allele frequency of SNP of MCP-1 at -2518 showed that the G/G genotype is low but the presence of allele A as well as the A-allele frequency are high in pSS (n = 52) as compared with healthy controls (n = 164). Immunohistochemistry showed in situ expression of MCP-1 and CCR2 in the ductal structure and infiltrating mononuclear cells (MNCs) of patients with pSS. Primary salivary epithelial cells in vitro from pSS produced MCP-1, which was significantly stimulated by IFN-gamma, as identified by both ELISA and RT-PCR. In contrast to MCP-1, CCR2 expression of primary salivary epithelial cells in vitro was not so changed by IFN-gamma. MCP-1 is involved in the disease susceptibility of pSS in the Japanese population. MCP-1 interactions with CCR2, which may be facilitated by IFN-gamma, are thought to perpetuate MNC infiltration into the salivary glands of SS.