Differential effects of interleukin 1α and 1β on cultured human and rat thyroid epithelial cells

Abstract

The effects of human recombinant interleukin 1\g=a\(20 pg/1-2 \g=m\g/l ) and 1\g=b\(200 pg/1-20 \g=m\g/l ) on two systems of thyroid cells have been compared. The thyroglobulin and cAMP secretion and the DNA content of human thyroid cells cultured in monolayer and of continuously grown rat thyroid cells, Fischer rat thyroid cell line have been studied. The growth of the rat thyroid cell line was inhibited by interleukin 1\ g=b\(20 ng/1-20 \g=m\g/l ), but not by interleukin 1\g=a\.None of the cytokines changed the cAMP production of the rat thyroid cells. In contrast, both cAMP production and thyroglobulin secretion were inhibited dose-dependently by the cytokines in human thyroid cells in secondary cultures. These results caution the interpretation and extrapolation of changes induced by interleukin 1 from one cell system to the other.Interleukin la (IL-la) and interleukin Iß (IL-Iß) belong to a group of bioactive polypeptides (mol wt 17 kD) produced by macrophages, but also by a broad spectrum of other cells (1). These cytokines are extremely potent and assumed to play a central role in immuno-inflammatory processes (1). IL-lß has also been recognised as a potent inhibitor of the function of endocrine tissues, such as rat pancreatic B-islets (2) and human thyroid cells in monolayer (3). In primary and secondary cultures of human thyroid cells, recombinant IL-lß (rIL-lß) (200 pg/1-20 p.g/1) inhibited both extracellular cAMP and thyroglobulin (Tg) secretion of the cells (3).The effects of IL-lß and IL-Ia appear to be me¬ diated through the same cell membrane receptor on lymphocytes, and probably, on other cells (1).Even so, IL-la has been shown to be more potent than IL-lß on a molar basis, particularly in the ac¬ tivation of T-and B-lymphocytes (1). The influ¬ ence and potency of IL-1 a on thyroid cells have not previously been reported.In the present study we compared the effect of rIL-la and rIL-lß on the function and growth of human secondary thyroid cultures and on the Fis¬ cher rat thyroid cell line (FRTL-5) (4) grown in monolayer and under similar culture conditions. FRTL-5 is a well characterized continuously grow¬ ing differentiated thyroid cell line convenient for repeptitive experiments (5). Material and Methods FRTL-5 cellsThe FRTL-5 cells (ATCC CRL 8305) were obtained from P. Ealey, University College Hospital, London, UK. The cells were grown as described by Ambesi-Impiombato et al. (4) in Ham's F12 medium modified by Coon (NordVacc, Stockholm, Sweden) supplemented with 5% new¬ born calf serum (NordVacc) penicillin (0.1 IU/1) strep¬ tomycin (100 mg/1) (NordVacc) and six growth factors (6H): bovine TSH 1 U/l (Armour, Kankakee, IL), human Parts of this study were presented in preliminary forms at

Expression of TPO and ThOXs in human thyrocytes is downregulated by IL-1α/IFN-γ, an effect partially mediated by nitric oxide

“…As already suggested by others, it appears that IL-1␣/IFN-␥ effects may involve interferences between cytokine-and TSHactivated pathways that would lead to the inactivation of the latter through impaired cAMP production (32,33). In addition, the thyroid-specific transcription factor-1 has been identified as a potential cellular target for IFN-␥ actions in FRTL-5 cells (28).…”

“…The hypothyroid status could therefore result not only from cell destruction by T lymphocyte-induced cell apoptosis (22,23) but also from thyroid hormone synthesis failure because of interferences in iodide transport and organification. IL-1-and IFN-induced disturbances in thyrocyte functions have already been widely reported in previous studies (1,3,(31)(32)(33)35). More recently, IFN-␥ has been reported to affect the expression of the iodide transporter NIS in a transgenic model of targeted IFN-␥ expression in the thyroid gland (7).…”

“…Previous studies (3,5,20,24,32) addressing IL-1-induced alterations in thyroid cell growth, morphology, and apoptosis showed variable results but were primarily generated with IL-1␤. Hence, human thyrocytes incubated with IL-1␤ exhibited striking morphological changes, including cytoplasmic retraction or dissociation (3).…”

“…Therefore, the specific effects induced by different cytokines should be carefully distinguished. For example, growth of FRTL-5 cells is inhibited by IL-1␤ but not by IL-1␣ (32). It is plausible that, preceding death, immunological injuries could affect thyroid cell functions and that defects in hormone synthesis might appear before cell destruction or, at least, independently from it.…”

Differential Effects of Acute and Chronic Exposure to Interferon-γ on Cyclic Adenosine 3′,5′-Monophosphate Response Element-Regulated Gene Expression1

“…Unlike these studies, which used recombinant human IL-1␤, our experiments were performed with rat rIL-1␤. Whether these differences reflect species-specific cytokine effects on rat thyroid cell growth is unknown, but has been discussed previously (14,43).…”