TNF-alpha, TSH, and aging regulate TGF-beta synthesis and secretion in FRTL-5 rat thyroid cells.
Tumor necrosis factor-alpha (TNF-alpha), a cytokine produced by macrophages in response to a variety of pathological conditions, can inhibit thyroid cell function in vitro and in vivo. TNF-alpha induction of transforming growth factor-beta 1 (TGF-beta 1) in rat endothelial cells suggested that TGF-beta, a known mediator of inflammatory effects of TNF-alpha, may be involved in the sensitivity of aged thyroid cells to TNF-alpha (G. Chen, A. E. Pekary, and J. M. Hershman. Endocrinology 131: 863-870, 1992). To determine whether TNF-alpha induces TGF-beta production in FRTL-5 cells, young (< 20 passages) and aged (> 40 passages) FRTL-5 cells were grown to near confluency in medium containing 2 U/l of bovine thyroid-stimulating hormone [TSH; 6-hormone (6H) medium] or no TSH [5-hormone (5H) medium]. TNF-alpha (0-100 ng/ml) was added 0-48 h before total RNA was extracted. Northern blots were hybridized with 32P-TGF-beta 1, -beta 2, and -beta 3 cDNAs. In aged cells TNF-alpha increased their TGF-beta 1 (and -beta 2 and -beta 3) mRNA levels 5.4-fold (and > 10-fold), respectively, while in young cells all TGF-beta mRNAs remained almost undetectable during incubation with TNF-alpha. In contrast, TNF-alpha and TSH had a highly significant stimulatory effect on the secretion rate of TGF-beta precursors in both young and old cells as measured in the mink lung cell bioassay.(ABSTRACT TRUNCATED AT 250 WORDS)
Pekary
A E
AE
Endocrine Research Laboratory, West Los Angeles Veterans Affairs Medical Center, California.
Berg
L
L
Wang
J
J
Lee
P
P
Dubinett
S M
SM
Hershman
J M
JM
D000818:Animals; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D013972:Thyrotropin