Interleukin-1 stimulates thyroid cell growth and increases the concentration of the c-myc proto-oncogene mRNA in thyroid follicular cells in culture.
In the course of studies of cell-mediated immunity in Graves' disease, we noted that normal peripheral blood monocytes, when stimulated by bacterial lipopolysaccharide, conditioned their media with a factor that had the physicochemical properties of the lymphokine interleukin-1 (IL-1) and that enhanced DNA synthesis and replication in quiescent FRTL5 cells, a line of nontransformed rat thyroid follicular cells. This finding led to the present studies, in which the effect of IL-1 (recombinant IL-1-p) on DNA synthesis in FRTL5 was explored. In the absence of serum, IL-1 induced a small, but significant, increase in [3H]thymidine incorporation into DNA. Calf serum (0.5%) alone also stimulated DNA synthesis slightly, but it greatly enhanced, in a synergistic manner, the stimulatory response to IL-1, decreasing the minimally effective concentration of IL-1 and amplifying the response to higher concentrations. A similar synergism was noted when quiescent FRTL5 were cultured with a combination of IL-1 and a low concentration of insulin-like growth factor-I (IGF-I), which itself stimulated DNA synthesis modestly. IL-1 also increased levels of the mRNA of the proto-oncogene c-myc in quiescent FRTL5, as TSH does, an effect thought to reflect commitment of the cell to increased growth. The findings indicate that IL-1 is an independent stimulator of thyroid cell growth, and that its effects are greatly enhanced by serum, probably in large measure by the IGF-I contained therein. They raise the possibility that IL-1 generated locally by intrathyroid macrophages may act directly by a short-loop mechanism to increase goiter formation in autoimmune thyroid disease.
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*
D007375:Interleukin-1; D012333:RNA, Messenger