Regulation of disease susceptibility and mononuclear cell infiltration into the labial salivary glands of Sjögren's syndrome by monocyte chemotactic protein-1.
OBJECTIVE
To investigate how monocyte chemotactic protein-1 (MCP-1) is involved in the pathological process of primary SS (pSS).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Iwamoto
Naoki
N
Department of Immunology and Rheumatology, Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Kawakami
Atsushi
A
Arima
Kazuhiko
K
Nakamura
Hideki
H
Kawashiri
Shin-ya
SY
Tamai
Mami
M
Kita
Junko
J
Okada
Akitomo
A
Koga
Tomohiro
T
Kamachi
Makoto
M
Yamasaki
Satoshi
S
Ichinose
Kunihiro
K
Ida
Hiroaki
H
Origuchi
Tomoki
T
Eguchi
Katsumi
K
D044466:Asian People / Q000235:genetics; D015153:Blotting, Western; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012470:Salivary Glands, Minor / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000473:pathology
D018932:Chemokine CCL2; D010446:Peptide Fragments; C069261:interferon gamma (1-39); D007371:Interferon-gamma