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

Abstract

Thyroid glands affected by Graves' disease (GD) show striking leukocytic infiltration, mainly by T-cells. The mechanisms by which the various leukocytes are maintained in the thyroid are unknown. Growth-regulated oncogene-(GRO-) in interaction with its receptor CXCR2 is a chemoattractant for both T-cells and neutrophils and may be one of the chemokines involved in the cell maintenance.GRO-and CD18 mRNA as a marker of leukocytic infiltration were quantified in thyroid tissue using competitive RT-PCR. We found very high GRO-mRNA levels in all thyroid tissues. In GD patients (n=16), the GRO-mRNA did not correlate with the CD18 mRNA level or thyroid peroxidase and TSH-receptor antibodies in patients' sera. In thyroid autonomy (n=10), the GRO-mRNA levels were significantly lower in autonomous single adenomas compared with the corresponding normal tissue.In order to define the cellular source of GROmRNA and protein, we examined various thyroidderived cells. Thyrocytes, thyroid-derived leukocytes and fibroblasts showed basal GRO-mRNA and protein expression, which was remarkably upregulated by different stimuli in vitro. The expression of GRO-by thyroid carcinoma cell lines confirms that thyrocytes may actually produce GRO-. As shown by flow cytometry and immunohistology, CD68 + monocytes/macrophages are the only cell population strongly expressing CXCR2 in the thyroid.

A Novel Model for Lymphocytic Infiltration of the Thyroid Gland Generated by Transgenic Expression of the CC Chemokine CCL21

“…However, most chemokines studied to date are expressed within the thyroids of GD and HT patients. These include CXC chemokines, CXCL1 (17), the IFN-␥ inducible chemokines CXCL9, and CXCL10 (9,18,19), CXCL12 (16), and CXCL13 (20). The CC chemokines CCL2, CCL3, CCL4, and CCL5 are also reported to be expressed in thyroid disease (19,21,22).…”

“…Indeed, CXCR3, CCR2, and CCR5 expression is elevated on infiltrating inflammatory cells relative to peripheral blood leukocytes (9,18,21,23). The cellular source of these chemokines in the thyroid is usually the infiltrating lymphocytes, but thyrocytes and fibroblasts also express chemokines in diseased thyroid (17). Different proinflammatory stimuli such as IL-1, IFN-␥, and TNF-␣ increase expression of chemokines by thyroid follicular cells in culture (17,18,24,25), suggesting that inflammatory cytokines may trigger expression of chemokines by thyrocytes and other resident thyroid cells in vivo.…”

“…The cellular source of these chemokines in the thyroid is usually the infiltrating lymphocytes, but thyrocytes and fibroblasts also express chemokines in diseased thyroid (17). Different proinflammatory stimuli such as IL-1, IFN-␥, and TNF-␣ increase expression of chemokines by thyroid follicular cells in culture (17,18,24,25), suggesting that inflammatory cytokines may trigger expression of chemokines by thyrocytes and other resident thyroid cells in vivo. Interestingly, recent studies have shown that chemokines required for the formation and maintenance of lymphoid follicles (i.e., CXCL12, CCL21, and CXCL13) are expressed in the thyroids of AITD patients (20,26).…”

CXCR6 within T-helper (Th) and T-cytotoxic (Tc) type 1 lymphocytes in Graves’ disease (GD)

“…3B), the levels were somewhat high compared with other chemokines quantified (21,25,28). Surprisingly, CXCL16 cDNA levels within the two HT tissues were within the same range as those of many GD and normal TA tissues.…”

Mechanism of Direct Hepatotoxic Effect of KC Chemokine: Sequential Activation of Gene Expression and Progression from Inflammation to Necrosis

“…8 Thyroid glands affected with Graves disease express GRO␣ at a high level, but there is no infiltration of neutrophils in the glands. 9 Overexpression of human IL-8 in the liver of transgenic mice did not result in accumulation of neutrophils within the liver, 10 although human IL-8 can cause chemotaxis of mouse neutrophils in vitro. 4 Likewise, injection of recombinant KC into the circulation of mice did not cause recruitment of neutrophils into the liver.…”