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Cytokine-Induced Lymphocyte Chemoattraction from Cultured Human Thyrocytes: Evidence for Interleukin-16 and Regulated upon Activation, Normal T Cell Expressed, and Secreted Expression

Department of Medicine (A.G.G., L.J.M., T.J.S.), Albany Medical College, Albany, New York 12208; Pulmonary Center (N.H., W.W.C.), Boston University School of Medicine, Boston, Massachusetts 02118; and Divisions of Endocrinology and Metabolism and Molecular Medicine (A.G.G., T.J.S.), Harbor-University of California Los Angeles Medical Center, Torrance, California 90502; and University of California Los Angeles School of Medicine, Los Angeles, California 90095

Address all correspondence and requests for reprints to: Terry J. Smith, M.D., Division of Molecular Medicine, Harbor-University of California Los Angeles Medical Center, Building C-2, 1124 West Carson Sreet, Torrance, California 90502-2064.

Mediators of lymphocyte infiltration in inflammatory thyroid disease have yet to be identified. Here we examine the ability of IL-1ß to enhance the production of chemoattractants by human thyrocytes. Primary cultures, when treated with the cytokine, release T lymphocyte chemotactic activity. The effect of IL-1ß is time dependent, and the chemoattraction activity can be partially attenuated by the addition of either anti-IL-16 or anti-regulated upon activation, normal T cell expressed, and secreted (RANTES) neutralizing antibodies. IL-16 is a CD4⁺-specific ligand, and RANTES is a C-C type chemokine that targets monocytes and lymphocytes. These chemoattractants could be detected by specific ELISAs in conditioned medium from IL-1ß treated thyrocytes. Northern analysis revealed that thyrocytes express high constitutive levels of IL-16 mRNA, which were invariant with regard to IL-1ß (10 ng/ml) or glucocorticoid treatment. RANTES mRNA was not detected in control cultures but was strongly induced by the cytokine. IL-16 but not RANTES expression was dependent on the activity of caspase-3. Pro-IL-16 protein could be detected in homogenates of thyroid tissue from patients with multinodular goiter and Graves’ disease. Thus, human thyrocytes, through the expression of chemoattractants, may participate in the recruitment of lymphocytes to the thyroid in inflammatory states.

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