GRO-alpha in normal and pathological thyroid tissues and its regulation in thyroid-derived cells

Area of Science:

• Endocrinology
• Immunology
• Molecular Biology

Background:

• Graves' disease (GD) involves significant T-cell infiltration in the thyroid gland.
• The mechanisms maintaining leukocyte presence in the thyroid are not fully understood.
• Growth-regulated oncogene-alpha (GRO-alpha) and its receptor CXCR2 are known chemoattractants for T-cells and neutrophils.

Purpose of the Study:

• To investigate the role of GRO-alpha in leukocyte infiltration in Graves' disease.
• To quantify GRO-alpha mRNA levels in thyroid tissues from GD patients and individuals with thyroid autonomy.
• To identify the cellular sources of GRO-alpha and its receptor CXCR2 within the thyroid.

Main Methods:

• Competitive RT-PCR was used to quantify GRO-alpha and CD18 mRNA in thyroid tissues.
• Analysis included thyroid tissues from Graves' disease patients (n=16) and thyroid autonomy (n=10).
• Flow cytometry and immunohistology were employed to identify cell populations expressing GRO-alpha and CXCR2.

Main Results:

• High GRO-alpha mRNA levels were detected in all thyroid tissues examined.
• In GD patients, GRO-alpha mRNA did not correlate with CD18 mRNA, thyroid peroxidase, or antibody levels.
• GRO-alpha mRNA levels were significantly lower in autonomous adenomas compared to normal thyroid tissue.
• Thyrocytes, leukocytes, and fibroblasts express GRO-alpha, with upregulation observed in vitro.
• Thyroid carcinoma cell lines also produced GRO-alpha, confirming thyrocyte production.
• CD68+ monocytes/macrophages were identified as the primary cell population expressing CXCR2 in the thyroid.

Conclusions:

• Thyrocytes are a source of GRO-alpha in the thyroid.
• While GRO-alpha is present, its expression does not directly correlate with leukocyte infiltration in Graves' disease.
• Monocytes/macrophages are the main cells expressing the GRO-alpha receptor CXCR2 in the thyroid.