Cytokines modulate type I iodothyronine deiodinase mRNA levels and enzyme activity in FRTL-5 rat thyroid cells.
Tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interferon-gamma (INF-gamma) have inhibitory effects on thyroid function both in vivo and in vitro. We have studied the effects of these cytokines on type I 5'-deiodinase (5'-DI) mRNA expression and enzyme activity in FRTL-5 cells maintained in standard cell culture medium containing 0 (5H) or 2 mIU/ml bovine TSH (6H). Northern blots were hybridized with 5'-DI cDNA. 5'-DI mRNA levels were reduced to 20% of control values after treating cells with 100 ng/ml TNF-alpha in 6H for 2 days while the corresponding enzyme activity was reduced 50%. Other cytokines, including IL-1beta and interferon-gamma, also significantly inhibited expression of 5'-DI in FRTL-5 cells grown in 6H medium. Because the majority of circulating T3 in the rat is secreted by the thyroid gland, the highly significant decline in the serum T3/T4 ratio following in vivo administration of cytokines may be due to their direct inhibitory effect on thyroidal 5'-DI expression.
Pekary
A E
AE
Endocrinology Research Laboratory, West Los Angeles VA Medical Center, University of California, 90073, USA.
Berg
L
L
Santini
F
F
Chopra
I
I
Hershman
J M
JM
D000818:Animals; D002417:Cattle; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D007453:Iodide Peroxidase / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D013961:Thyroid Gland / Q000378:metabolism*
D016207:Cytokines; D012333:RNA, Messenger; D007453:Iodide Peroxidase