Karrer, Sigrid and Bosserhoff, Anja Kathrin and Weiderer, Petra and Distler, Oliver and Landthaler, Michael and Szeimies, Rolf-Markus and Mueller-Ladner, Ulf and Schoelmerich, Juergen and Hellerbrand, Claus (2005) The-2518 promotor polymorphism in the MCP-1 gene is associated with systemic sclerosis. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 124 (1). pp. 92-98. ISSN 0022-202X, 1523-1747
Full text not available from this repository. (Request a copy)Abstract
Factors influencing the initiation or progression of sclerosis in patients with systemic sclerosis (SSc) are poorly understood. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine, which is upregulated in fibroblasts during development of sclerosis. In this study, we investigated the frequency of the functional -2518G MCP-1 promoter polymorphism in 18 patients with SSc and 139 healthy controls. In the lesional skin of the same SSc patients, expression of MCP-1 protein was examined by immunohistochemistry. To investigate a genotype/phenotype correlation, basal as well as tumor necrosis factor (TNF)-induced MCP-1 expression was analyzed in fibroblasts isolated from the skin of SSc patients with different MCP-1 genotypes by quantitative RT-PCR and ELISA. Genotyping for the -2518 (A/G) MCP-1 promotor polymorphism showed that GG homozygotes were significantly more frequent in patients with SSc than in controls (28%vs 6%). Results of immunohistochemistry revealed that MCP-1 was expressed in keratinocytes, infiltrating inflammatory cells, fibroblasts, and endothelial cells in scleroderma skin, whereas normal control skin showed no MCP-1 expression. MCP-1 expression in fibroblasts from GG-homozygote individuals tended to be stronger as compared to AG or AA genotypes. Furthermore, basal as well as TNF-induced MCP-1 expression of fibroblasts isolated from a GG-homozygote SSc patient was significantly higher than MCP-1 expression of fibroblasts isolated from heterozygote or AA-homozygote donors. The A -2518G polymorphism of the MCP-1 gene appears to affect MCP-1 expression of skin fibroblasts of patients with SSc. In accordance, the G/G genotype may predispose patients to SSc.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MONOCYTE CHEMOATTRACTANT PROTEIN-1; CHEMOTACTIC PROTEIN-1; PULMONARY-FIBROSIS; REGULATORY REGION; EXPRESSION; FIBROBLASTS; SCLERODERMA; DISEASE; SUSCEPTIBILITY; CHEMOKINES; chemokine; fibrosis; monocyte chemotactic protein-1; scleroderma; tumor necrosis factor |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Jun 2021 12:36 |
| Last Modified: | 07 Jun 2021 12:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36736 |
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