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Reduced expression of stromal-derived factor 1 in autonomous thyroid adenomas and its regulation in thyroid-derived
G Aust1, M Steinert, S Kiessling
1Institute of Anatomy, University of Leipzig, Leipzig 04103, Germany. ausg@medizin.uni-leipzig.de
Abstract:
Stromal-derived factor 1 (SDF-1) and CXCR4 comprise a unique chemokine/chemokine receptor pair, exhibiting important functions in morphogenesis and growth regulation as well as attractant properties on T lymphocytes. No data are available on SDF-1 and CXCR4 in normal or pathological thyroid tissues. SDF-1, CXCR4, and CD18 messenger ribonucleic acid (mRNA) as a marker of leukocytic infiltration were quantified in tissues affected by thyroid adenoma (n = 11) and Graves' disease (GD; n = 16) using competitive RT-PCR. SDF-1 mRNA levels differed significantly between autonomous adenomas and the corresponding normal tissue, but not in GD between patients with low or high leukocyte infiltration, thyroid peroxidase, and TSH receptor autoantibodies, respectively. We found a strong correlation between CXCR4 and CD18 mRNA, which indicates CXCR4 expression by leukocytes. To define the cellular source of SDF-1 and CXCR4 in thyroid tissue, we examined various thyroid-derived cells. Fibroblasts are the most potent producers of SDF-1, although thyrocytes also secrete SDF-1 in vitro. Leukocytes showed very weak SDF-1 mRNA levels and no secretion of the chemokine. Immunohistology confirmed and extended these results; SDF-1 expression was found in fibroblasts, but not or very weakly in CD45(+) leukocytes and thyrocytes. Only leukocytes were CXCR4(+). As examined by flow cytometry, the number of CD3(+) T cells expressing CXCR4 is significantly higher in the thyroid than in peripheral blood. SDF-1 seems to be involved in thyroid tissue homeostasis in thyroid adenoma, but not in the maintenance of lymphocytic infiltration in GD.
Insights
Stromal-derived factor 1 (SDF-1) and its receptor CXCR4 are present in thyroid tissues. Fibroblasts produce SDF-1, while leukocytes express CXCR4, suggesting roles in thyroid adenoma but not Graves' disease.
Area of Science:
- Endocrinology
- Immunology
- Molecular Biology
Background:
- Stromal-derived factor 1 (SDF-1) and CXCR4 are crucial for cell signaling and migration.
- Their roles in normal and pathological thyroid tissues remain largely uncharacterized.
Purpose of the Study:
- To investigate the expression and cellular localization of SDF-1 and CXCR4 in thyroid adenoma and Graves' disease (GD).
- To determine the cellular sources of SDF-1 and CXCR4 within thyroid tissue.
Main Methods:
- Competitive RT-PCR was used to quantify SDF-1, CXCR4, and CD18 mRNA levels in thyroid tissues.
- Immunohistochemistry and flow cytometry were employed to identify cellular expression patterns.
Main Results:
- SDF-1 mRNA levels were significantly altered in thyroid adenomas compared to normal tissue.
- A strong correlation between CXCR4 and CD18 mRNA suggests CXCR4 expression on leukocytes.
- Fibroblasts were identified as the primary source of SDF-1, while thyrocytes also secreted it.
- Leukocytes expressed CXCR4, with significantly higher numbers of CXCR4-positive T cells in thyroid tissue compared to peripheral blood.
Conclusions:
- SDF-1 plays a role in thyroid tissue homeostasis in adenomas.
- SDF-1 and CXCR4 do not appear to maintain lymphocytic infiltration in Graves' disease.
- The findings highlight differential roles of the SDF-1/CXCR4 axis in thyroid pathologies.