PMID- 2474435
OWN - NLM
STAT- MEDLINE
DCOM- 19890920
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 125
IP  - 3
DP  - 1989 Sep
TI  - Influence of cytokines on growth and differentiated function of FRTL5 cells.
PG  - 1260-5
AB  - A functioning rat thyroid cell line (FRTL5) was used to study interactions of TSH 
      with interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha). We 
      examined effects on growth and differentiated function. Growth was assessed by 
      DNA, incorporation of [3H]thymidine ([3H]Tdr) into DNA, and cell number; uptake 
      of 125I (I- uptake) and the concentration of cAMP were measured simultaneously 
      with growth assessment. IFN gamma stimulated the 30-min I- uptake and enhanced 
      the effect of TSH. TNF alpha had minimal effects on growth indices (slight 
      increase in [3H]Tdr incorporation) and had no influence on I- uptake; it 
      inhibited TSH stimulation of both growth and I- uptake. When combined, IFN gamma 
      and TNF alpha synergized in inhibiting TSH-stimulated growth. By itself TNF alpha 
      inhibited stimulation of I- uptake by TSH, but augmented the enhancement seen 
      with IFN gamma. The influence of calf serum (CS) was to increase the rate of 
      incorporation of [3H]Tdr, but a similar qualitative pattern for the actions of 
      the cytokines remained. A reverse profile (stimulation by IFN gamma, inhibition 
      by TNF alpha, and stimulation by the combination) was seen for I- uptake, with CS 
      increasingly diminishing all values. TSH stimulation of growth was progressively 
      effective with increments of CS in the medium, but consistently there was 
      inhibition that was greater with IFN gamma than with TNF alpha and was almost 
      total with the combined cytokines. Stimulation of I- uptake by TSH was enhanced 
      by IFN gamma, reduced by TNF alpha, and, when serum was present, increased to a 
      degree that was greater than additive by the combined cytokines. Growth 
      stimulation by insulin or insulin-like growth factor-I was inhibited partially by 
      the individual cytokines and completely by the combination. Both insulin and 
      insulin-like growth factor-I inhibited TSH stimulation of I- uptake, but similar 
      stimulation by the cytokines was not affected. Simultaneous with inhibition of 
      TSH-stimulated growth, both IFN gamma and TNF alpha enhanced cAMP accumulation. 
      The mechanism of these multiple effects of IFN gamma and TNF alpha, especially on 
      the actions of TSH, may not currently be fully explained, but they almost 
      certainly reflect differing modes of action. The relevance to thyroid function in 
      man is conjectural. Especially in Graves' disease, where thyroid infiltration 
      with cells that secrete these cytokines is common, it seems probable that both 
      IFN gamma and TNF alpha will have significant influences on both growth and 
      differentiated cell function.
FAU - Zakarija, M
AU  - Zakarija M
AD  - Department of Medicine, University of Miami School of Medicine, Florida 33101.
FAU - McKenzie, J M
AU  - McKenzie JM
LA  - eng
GR  - DK-31391/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Biological Factors)
RN  - 0 (Cytokines)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9002-71-5 (Thyrotropin)
RN  - E0399OZS9N (Cyclic AMP)
RN  - TBT296U68M (1-Methyl-3-isobutylxanthine)
SB  - IM
MH  - 1-Methyl-3-isobutylxanthine/pharmacology
MH  - Animals
MH  - Biological Factors/*pharmacology
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Cell Line
MH  - Cyclic AMP/metabolism
MH  - Cytokines
MH  - DNA Replication/drug effects
MH  - Interferon-gamma/*pharmacology
MH  - Recombinant Proteins/pharmacology
MH  - Thyroid Gland/*cytology/drug effects
MH  - Thyrotropin/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1989/09/01 00:00
MHDA- 1989/09/01 00:01
CRDT- 1989/09/01 00:00
PHST- 1989/09/01 00:00 [pubmed]
PHST- 1989/09/01 00:01 [medline]
PHST- 1989/09/01 00:00 [entrez]
AID - 10.1210/endo-125-3-1260 [doi]
PST - ppublish
SO  - Endocrinology. 1989 Sep;125(3):1260-5. doi: 10.1210/endo-125-3-1260.