title: Regulation of disease susceptibility and mononuclear cell infiltration into the labial salivary glands of Sjögren's syndrome by monocyte chemotactic protein-1.
abstract: 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.
authors.affiliation: Department of Immunology and Rheumatology, Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Iwamoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawakami
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arima
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Shin-ya
authors.initials: SY
authors.lastname: Kawashiri
authors.forename: Mami
authors.initials: M
authors.lastname: Tamai
authors.forename: Junko
authors.initials: J
authors.lastname: Kita
authors.forename: Akitomo
authors.initials: A
authors.lastname: Okada
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Koga
authors.forename: Makoto
authors.initials: M
authors.lastname: Kamachi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Ichinose
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ida
authors.forename: Tomoki
authors.initials: T
authors.lastname: Origuchi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
mesh_terms: 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
chemical_list: D018932:Chemokine CCL2; D010446:Peptide Fragments; C069261:interferon gamma (1-39); D007371:Interferon-gamma