河南省新乡市新延路

        新乡医学院免疫学教研室

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  E-mail: wanghui01@371.net

1984年毕业于新乡医学院

1987-1990 在西安医科大学微生物与免疫学教研室，师从于铁衣教授攻读免疫学研究方向硕士学位

1995-1999 在中国医学科学院、中国协和医科大学、北京协和医院、卫生部内分泌重点实验室，师从于史轶蘩院士和邓洁英教授，在职攻读博士学位。主要从事神经内分泌免疫学方面的研究。

熟悉的领域: 免疫学、分子生物学、微生物学和内分泌学

业余爱好: 网页制作和结交朋友

博士论文英文摘要

(abstract)

Besides the primarily known effects of growth and development on body, GH has also been demonstrated to influence the development and function of immune system. Recently, it has become increasingly evident that there is GH receptor on lymphocytes and lymphocytes can produce growth hormone, which is named as immunoreactive growth hormone (irGH) of lymphocytes secretion. GH can act as a messenger in the communication between neuroendocrine and immune systems, leading to the keeping of physiological balance and stabilization of body. Now, the relationship of GH and lymphocytes function has become a focus of the research realm of neuro-endocri-immune network. As most of the research localize on cellular level, the results of experiments are diverse. In order to understand the relationship of GH and lymphocytes, this study is to explore the regulation mechanism of lymphocyte irGH from molecular level and the autocrine or endocrine effects of GH on the expression of IL-2R, secretion of IL-2 and IFN-γin T lymphocytes.

In the present study, a pair of oligodeoxynuclotide primers was designed and synthesized according to the nucleotide sequence of human pituitary growth hormone gene. The irGH DNA fragment (-484--+2bp) was obtained by PCR with lymphocyte DNA of normal human peripheral blood as template. Then, the plasmid of PGEM7Zf (+)-irGH DNA(-484—+2bp) was constructed by ligation of irGH DNA with PGEM7Zf(+), transformation, blue/white color selection and restriction enzyme analysis. The 5'-flanking region of irGH was sequenced by sanger’s dideoxynucleitide chain-termination reaction. It was demonstrated that the sequence data of 5'-flanking region (-484--+2bp) in irGH gene was identical to that of pituitary GH gene.

The 5'-flanking region of irGH was inserted into the PGL2-Basic vector, and was constructed as PGL2-GH-luc luciferase reporter gene plasmid. We transfected it into Jurkat cells, and investigated the effects of GH, GHRH, TRH, IGF－1 and SS on the secretive regulation of lymphocytes irGH. The results showed that GH and GHRH could inhibit the expression of irGH（about 50％）in a non-dose-related manner. High concentration of SS and TRH （100nM） could also inhibit the expression of irGH（about 85％）， our results indicated that the regulation of irGH secretion from lymphocytes was different from that of pituitary GH.

After transfected PGL2-GH-LUC plasmid into Jurkat cells, we investigated the effects of IL－1β, IL－2, IL－6, TNF－β, and IFN－γon the regulation of irGH secretion by lymphocytes. The results showed that IL－1β, TNF－βand IFN－γof physiological dose could inhibit the expression of lymphocytes irGH, high concentration of IL－6 and IL-2（100u－1000u） could also inhibit the expression of lymphocytes irGH . Thus a lot of hormones and cytokines could inhibit the expression of irGH, which may be one of the reasons that the secretion of irGH from lymphocytes is very little.

On the other hand, we inserted GH cDNA into PcDNA3.1 vector, and constructed the expression plasmid of PcDNA-GH cDNA. After transfecting it into Jurkat cells, we investigated the effects of locally secreted GH on the function of lymphocytes. The results demonstrated that GH secreted autocrinelly could increase the expression of IL-2R and secretion of IL-2 and IFN-γ in Jurkat cells after PHA activation, but these expression of IL－2R, IL－2 and IFN－γ was brought down by the treatment of GH antibody. These results support the idea that irGH is an autocrine and paracrine factor, and can regulate the function of lymphocytes.

In order to study the effects of endocrine GH on the function of lymphocytes, we treated Jurkat cells with different doses of rhGH（1μg/L, 3μg/L, 25μg/L and 100μg/L）rhGH，and observed the changes of IL－2R on Jurkat cells and the amount of IL-2, IFN－γin medium. The results demonstrated that GH could promote the expression of IL－2R on Jurkat cells, the effect of GH was decreasing with raise of dose, but GH could promote secretion of IL－2 in a dose-related manner. The concentration of IFN－γ was the highest when the concentration of rhGH was 3μg/L in medium.

It is known that pit-1 is a member of the POU family which is transcription factor regulating mammalian anterior pituitary development during development. The pit-1 gene expresses before expression of GH and PRL gene in the somatotroph and lactotrope, respectively, and is thought to be the major cell-specific activator of hormone expression in these two cell types. I want to know the effect of pit-1 protein on the secretion of irGH. I have constructed the pit-1 gene expression plasmid(PcDNA3.1-pit-1cDNA), I am co-transfect the PcDNA3.1-pit-1cDNA into Jurkat cells with PGL2-5*GH-LUC , it has been demonstrated that the secretion of irGH do not dependent on pit-1 protein.

The study indicate that the regulation of irGH secretion from T lymphocytes is different from that of pituitary GH, some cytokines can regulate the secretion of irGH from T lymphocytes, the GH secreted autocrinelly and pituitary GH can regulate the function of lymphocytes. These results indicate that the relationship of neuroendocrine and immune system is very close, meanwhile, they could provide some theoretical bases for the widely clinical use of human recombinant GH.

发表论文

抑制素的研究进展   国外医学免疫学分册1996年 19卷 第2期

淋巴细胞分泌的免疫反应性生长激素的研究进展 国外医学免疫学分册1997年第20卷第4期

人淋巴细胞免疫反应性生长激素基因调控序列的克隆与鉴定 中国免疫学杂志1999年第15卷第1期 

生长激素调节T淋巴细胞的功能 中国免疫学杂志2000年第16卷第9期 

生长激素对免疫细胞的调节作用 国外医学内分泌分册2000年第20卷第2期

T淋巴细胞生长激素基因表达调控的研究 中国免疫学杂志 2001年待发表