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J Biol Chem, Vol. 274, Issue 22, 15622-15632, May 28, 1999

Prostaglandin-endoperoxide H Synthase-2 Expression in Human Thyroid Epithelium
EVIDENCE FOR CONSTITUTIVE EXPRESSION IN VIVO AND IN CULTURED KAT-50 CELLS

Terry J. Smith^§, Timothy A. Jennings, Daniela Sciaky, and H. James Cao

From the  Division of Molecular and Cellular Medicine, Department of Medicine, the ^§ Department of Biochemistry and Molecular Biology, and the  Department of Pathology, Albany Medical College and the Samuel S. Stratton Veterans Affairs Medical Center, Albany, New York 12208

Prostaglandin-endoperoxide H synthase (PGHS) (EC 1.14.99.1) expression was examined in human thyroid tissue and in KAT-50, a well differentiated human thyroid epithelial cell line. PGHS-1 is found constitutively expressed in most healthy tissues, whereas PGHS-2 is highly inducible and currently thought to be expressed, with few exceptions, only in diseased tissues. Surprisingly, PGHS-2 mRNA and protein were easily detected in normal thyroid tissue. KAT-50 cells express high levels of constitutive PGHS-2 mRNA and protein under basal culture conditions. Compounds usually associated with PGHS-2 induction, including interleukin-1 (IL-1), phorbol 12-myristate 13-acetate, and serum transiently down-regulated PGHS-2 expression. Human PGHS-2 promoter constructs (1840/+123 and 831/+123) fused to a luciferase reporter and transfected into untreated KAT-50 cells exhibited substantial activity. NS-398, a highly selective inhibitor of PGHS-2 could inhibit substantial basal prostaglandin E₂ production. Exogenous IL-1 receptor antagonist or IL-1 neutralizing antibodies could attenuate constitutive PGHS-2 expression in KAT-50 cells, suggesting that endogenous IL-1 synthesis was driving PGHS-2 expression. Our findings suggest that normal thyroid epithelium expresses high constitutive levels of PGHS-2 in situ and in vitro and this enzyme is active in the generation of prostaglandin E₂. Thus, unprovoked PGHS-2 expression might be considerably more widespread in healthy tissues than is currently believed.

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