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Study Of The Crosstalk Of Interleukin-2 And Estrogen And Their Receptors

Posted on:2003-06-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y Q ZhongFull Text:PDF
GTID:1104360062990720Subject:Physiology
Abstract/Summary:PDF Full Text Request
With the establishment of nueroimmunoendocrinology, many reports had suggested a complex interplay between the neuroendocrine and immune systems. The cross-talk between the neuroendocrine and immune system is now well demonstrated. These systems use similar ligands and receptors to establish a physiological intra- and inter-system communication circuitry that plays an important role in homeostasis. Interleukin-2(IL-2) a cytokine secreted by activated T lymphocytes, plays an essential role in the growth and differentiation of T cells, natural killer cells and other cells involved in immune responses. Recently it has become appreciated that IL-2 may have a direct role in growth and function of non-immune cell types such as neurons and endocrine cells. Estrogens(E) are steroid hormones that have profound effects on both the female and the male reproductive systems. Increasing evidence has placed E among potent immunomodulators, participating in various aspects of immune system function in both health and disease. Females are immunologically stronger than males, and the change of body's E level has been tied up with the development of immune apparatus development, the function of immune system and many kinds of autoimmune disease. It would help for the learning of Neuro-Immun-Endocrine network by studding of the cross-talk between IL-2 and E and their receptors.Recent experiment of our lab showed that IL-2 and estradiol(E2) have some cross-talk in rat anterior pituitary(AP). For example, there are IL-2 and IL-2Ra,p,y subunits like immunoreactive substances localized in AP of normal rats. Theintensity of IL-2 immunoreactive staining and the number of IL-2 immunoreactive cells in AP of female rats were decreased significantly after the treatments of E2(25 (ig/kg/day) for 2 weeks. On the contrary the intensity of IL-2R immunoreactive staining and the number of IL-2R immunoreactive cells hi AP increased significantly by injection of ?, especially of IL-2RP and y chains. IL-2 at the concentration of 10 U/ml to 500 U/ml can significantly improve the proliferation of female rat AP cells, and it's effect on AP cells had some relation with the body's ? level. After the treatment of 10 u.g/ml IL-2 for 48 h, the ERa mRNA expression was upregulated while that of ERP was down regulated.There are still many questions that remain unclear. Such as if normal rat AP cells can express IL-2Rcc,p,y subunits' mRNA; are the upregulation of AP IL-2R immunostaining the results of the increase of its' mRNA expression? Do the effect of E to AP IL-2 and IL-2R have some relation with AP ERs? Can E have the same effect on the IL-2 and IL-2R expression in other tissues?In these experiments, methods of semi-quantity reverse transcription polymerase chain reaction(RT-PCR), immunohistochemistry, MTT method, 3H-TdR incorporation assay, unmunocytochemistry, flow cytometery and laser scanning confocal microscope methods were employed to investigate the IL-2R and ER expression in the normal rat AP, uterus, spleen and thymus, and the effect of ? level on the IL-2R and ER's expression. We also investigated the expression of IL-2R in breast cancer cell lines MCF-7(which is ERa positive) and MDA-MB-231 (which is ERP positive) and observed the effect of IL-2 on these cells proliferation.The main results are as follows:1. With the method of semi-quantity RT-PCR, we found there are expression of IL-2Ra,P,y chain's mRNA in both normal female rat AP tissue and cultured AP cells. IL-2 at the concentration of 500 U/ml can improve the expression of IL-2 and IL-2R of cultured AP cells after treatment of 72 h. E2(100 ug/kg/day) treat for 30 d can upregulate the expression of IL-2R in AP tissue, but hi vitro treatment of E2(10~6M) have little effect in AP cells IL-2R expression .2. There are IL-2RP and y like immunoreactive substance localized hi uterus endometrium of normal female rats. And the mRNA of all the there chain of IL-2R can be detected hi rat uterus. After ovariectomy(OVX) 30d, the IL-2Ryimmunoreactive positive cells are...
Keywords/Search Tags:interleukin-2, interleukin-2 receptor, estrogen, estrogen receptor, estradiol, anterior pituitary, uterus, spleen, thymus, breast cancer, crosstalk
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