Influence of cytokines on expression of thyrotropin receptor and adipogenesis in patients with Graves ophthalmopathy during the adipogenesis of orbital adipocytes

Yuqing YAN; Jianfeng HE; Kaijun LI

ABSTRACT

BACKGROUND:

Thyroid-stimulating hormone receptor is an autoantigen shared by thyroid follicuar cells and ocular orbital tissues,and cytokines plays an important role on the pathogenesis of Graves ophthalmopathy(GO) . It is still a puzzle that the relation of cytokines and thyroid-stimulating hormone receptor in the pathogenesis of GO.

OBJECTIVE:

To study the influence of various cytokines on the expression of thyroid-stimulating hormone receptor in the process of adipogenesis of in vitro cultured orbital adipose cells in GO patients. DESIGN,TIME AND

SETTING:

A single sample observation was carried out in the Central Laboratory,Department of Ophthalmology,Sun Yat-sen University(Guangzhou,Guangdong,Province) from September 2003 to March 2004. MATERIALSOrbital adipose cells were obtained from eight serious GO patients undergoing orbital decompression. Recombinant human interleukin 2(IL-2) ,IL-4,IL-6,IL-10,and interferon ?(IFN-?) were purchased from PEORO TECH EC Company.

METHODS:

Orbital adipose cells were cultured and treated by groups. IL-2,IL-4,IL-6,IL-10 and IFN-? was added to the culture media in the experimental group,while no any cytokine was given in the untreated group,and orbital adipose cells were primarily cultured in the control group. The cells were all collected twelve days later. MAIN OUTCOME

MEASURES:

The expression of thyroid-stimulating hormone receptor was examined with reverse transcriptase-polymerase chain reaction,and the content of cyclic adenosine monophosphate was measured with simultaneous radioimmunoassay. The quantitation of adipose in cells was detected by staining intracytoplasmic lipids with oil red O.

RESULTS:

The expression of thyroid-stimulating hormone receptor was significantly higher in cells treated with IL-2,IL-4,IL-6 and IL-10 than that in the untreated cells and in the cells treated with IFN-?. Treatment of GO orbital adipose cells with IL-2,IL-4,IL-6 and IL-10 during differentiation resulted in significantly greater cyclic adenosine monophosphate production by different degrees. The highest production achieved in the treatment with IL-6,which was two times as many as control group. The cyclic adenosine monophosphate production was significantly lower in the cells treated with IFN-? than in the untreated cells.

CONCLUSION:

IL-6,IL-4 and IL-10 can upregulate the expression of thyroid-stimulating hormone receptor in the orbital adipose cells of GO patients,and stimulate adipose differentiation. Conversely,IFN-? can restrain this process.