AJP - Regulatory, Integrative and Comparative Physiology, Vol 268, Issue 3 808-R815, Copyright © 1995 by American Physiological Society
TNF-alpha, TSH, and aging regulate TGF-beta synthesis and secretion in FRTL-5 rat thyroid cells
A. E. Pekary, L. Berg, J. Wang, P. Lee, S. M. Dubinett and J. M. Hershman
Endocrine Research Laboratory, West Los Angeles Veterans Affairs Medical Center, California.
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)
