Prostaglandin-endoperoxide H synthase-2 expression in human thyroid epithelium - Evidence for constitutive expression in vivo and in cultured KAT-50 cells
Tj. Smith et al., Prostaglandin-endoperoxide H synthase-2 expression in human thyroid epithelium - Evidence for constitutive expression in vivo and in cultured KAT-50 cells, J BIOL CHEM, 274(22), 1999, pp. 15622-15632
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.