Exp Mol Med.  1997 Mar;29(1):45-51.

Hormonal regulation of ICAM-1 gene expression in thyroid cells, FRTL-5

• An BS
• Ku BJ
• Park SY
• Shin JK
• Lee JH
• Kim YK
• Shong MH
• Ro HK

Abstract

Our previous works have shown that human thyroid follicular cells from Graves' disease and FRTL-5 rat thyroid cells express the intercellular adhesion molecule-1 (ICAM-1) molecule and its expression is upregulated by several cytokines, interferon-gamma, tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6. We used FRTL-5 cells which show hormonal dependence of growth and function for the study of hormonal regulation of ICAM-1 gene, We studied ICAM-1 mRNA expression and promoter regulation after cloning of rat ICAM-1 promoter. We found very interesting findings that thyroid stimulating hormone (TSH) and forskolin downregulates steady state MHC class land ICAM-1 mRNA levels in FRTL-5 cells; furthermore, TSH/cAMP inhibit cytokines (interferon-gamma,tumor necrosis factor-alpha)-mediated maximal ICAM-1 mRNA expression, In addition, hydrocortisone and insulin differentially regulate the ICAM-1 mRNA levels; hydrocortisone markedly suppresses the mRNA level but insulin partially recovers hydrocortisone mediated ICAM-1 suppression, The interferon-gamma and tumor necrosis factor-alpha increases full ICAM-1 promoter (pCAM-1822) activity and this cytokine mediated increase of the promoter activity is also inhibited by TSH and forskolin, Thus TSH/cAMP pathways play roles as a antagonistic action for maximal expression of ICAM-1 gene by these cytokines. We propose this TSH action is one of physiologic mechanisms to preserve self tolerance in face of abnormal cytokine challenges in systemic inflammatory condition or acute phase response.

Keyword

thyrotropin; cAMP; rat ICAM-1; thyroid; FRTL-5; cytokines

MeSH Terms

Animals
Clone Cells
Cloning, Organism
Colforsin
Cytokines
Gene Expression*
Graves Disease
Humans
Hydrocortisone
Insulin
Intercellular Adhesion Molecule-1*
Interferon-gamma
Interleukin-1beta
Interleukin-6
Necrosis
Rats
RNA, Messenger
Self Tolerance
Thyroid Gland*
Thyrotropin
Tumor Necrosis Factor-alpha
Colforsin
Cytokines
Hydrocortisone
Insulin
Intercellular Adhesion Molecule-1
Interferon-gamma
Interleukin-1beta
Interleukin-6
RNA, Messenger
Thyrotropin
Tumor Necrosis Factor-alpha