Differential cytokine regulation of MHC class II and thyroglobin mRNAs in rat thyroid cells.
We have previously demonstrated that recombinant gamma-interferon (gamma IF) inhibits thyroid cell proliferation in vitro. We now demonstrate differential regulation of thyroid cell genes by recombinant gamma IF, as evidenced by data obtained measuring thyroglobulin (Tg) mRNA and MHC class II alpha-chain mRNA transcripts. Using the rat thyroid cell clone 1B-6, derived from FRTL-5 cells, gamma IF markedly increases MHC class II (RT1.D) alpha-chain transcripts in proliferating cells. Simultaneously, Tg mRNA transcript levels are markedly inhibited, even in the presence of TSH and insulin-like growth factor I (as insulin), known stimulators of Tg mRNA. Similar data were obtained for both FRTL-5 and FRTL parent cell lines. Furthermore, using probes to the 5' region of the rat Tg gene we recognized not just a 9.0-kilobase (kb) mRNA, but also an additional 1.1-kb message in all proliferating thyroid cell cultures, suggesting truncation or alternative splicing of the Tg mRNA. Both the 9.0- and 1.1-kb mRNAs were inhibited by gamma IF. These data add further complexity to the cytokine regulation of thyroid cell gene expression and advise caution in making the assumption that thyroid cells may be efficient thyroid antigen-presenting cells in thyroid autoimmune disease.
Graves
P
P
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
Neufeld
D S
DS
Davies
T F
TF
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D015342:DNA Probes; D005796:Genes / Q000187:drug effects*; D005802:Genes, MHC Class II / Q000187:drug effects*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D051381:Rats; D011994:Recombinant Proteins; D013954:Thyroglobulin / Q000235:genetics*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
D015342:DNA Probes; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D013954:Thyroglobulin