Autoinduction of tumor necrosis factor-alpha in FRTL-5 rat thyroid cells.
Tumor necrosis factor-alpha (TNFalpha) may play a role in the development of autoimmune thyroiditis such as Hashimoto's thyroiditis. In the present study, we examined whether TNFalpha induced its own expression in FRTL-5 rat thyroid cells. Lipopolysaccharide (LPS) markedly increased TNFalpha mRNA levels in FRTL-5 cells as assessed by semiquantitative RT-PCR. In addition, LPS-stimulated cells released TNFalpha protein into the culture medium. Similarly, TNFalpha induced its own gene and protein expression in FRTL-5 cells as assessed by RT-PCR and metabolic labeling and immunoprecipitation of TNFalpha. The autoinduction of TNFalpha gene was also observed in TNFalpha-stimulated human thyroid epithelial cells. TNFalpha induction was specific to LPS and TNFalpha since interferon-alpha or amiodarone failed to increase TNFalpha mRNA levels in FRTL-5 cells. Human TNFalpha induced rat TNFalpha gene expression, indicating that type 1 TNF receptor (TNF-R) is involved in the autoinduction. TNFalpha did not increase either type 1 or type 2 TNF-R mRNA levels, suggesting that upregulation of TNF receptors is not involved in the autoinduction of TNFalpha. Although the biological significance of autoinduction of TNFalpha remains unclear, our results suggest that thyroid epithelial cells may participate in the development of autoimmune thyroiditis through production of TNFalpha. Furthermore, inhibition of TNFalpha production in the thyroid may represent a novel approach to mitigating inflammation in autoimmune thyroiditis.
Mori
Kouki
K
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. kokimori@mail.tains.tohoku.ac.jp
Yoshida
Katsumi
K
Komatsu
Ayumi
A
Tani
Jun-ichi
J
Nakagawa
Yoshinori
Y
Hoshikawa
Saeko
S
Ito
Sadayoshi
S
D000199:Actins / Q000032:analysis; D000818:Animals; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology*; D005786:Gene Expression Regulation; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000032:analysis; D047468:Immunoprecipitation; D051381:Rats; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000032:analysis; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases