Prostaglandin-endoperoxide H synthase-2 expression in human thyroid epithelium - Evidence for constitutive expression in vivo and in cultured KAT-50 cells

zProstaglandin-endoperoxide H synthase (PGHS) (EC 1.14.99.1) expression was examined in human thyroid tissue and in KAT-50, a well differentiated huma n thyroid epithelial cell line. PGHS-1 is found constitutively expressed in most healthy tissues, whereas PGHS-2 is highly inducible and currently tho ught to be expressed, with few exceptions, only in diseased tissues. Surpri singly, PGHS-2 mRNA and protein were easily detected in normal thyroid tiss ue. KAT-50 cells express high levels of constitutive PGHS-2 mRNA and protei n under basal culture conditions, Compounds usually associated with PGHS-8 induction, including interleukin-1 beta (IL-beta), phorbol la-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 rep orter and transfected into untreated KAT-50 cells exhibited substantial act ivity. NS-398, a highly selective inhibitor of PGHS-2 could inhibit substan tial basal prostaglandin E-2 production, Exogenous IL-1 receptor antagonist or IL-1 alpha neutralizing antibodies could attenuate constitutive PGHS-2 expression in KAT-50 cells, suggesting that endogenous IL-1 alpha synthesis was driving PGHS-2 expression, Our findings suggest that normal thyroid ep ithelium expresses high constitutive levels of PGHS-2 in situ and in vitro and this enzyme is active in the generation of prostaglandin E-2. Thus, unp rovoked PGHS-2 expression might be considerably more widespread in healthy tissues than is currently believed.