人免疫细胞产生降钙素基因相关肽的规律及其临床意义

Human T lymphocyte mitogen, such as PHA can time- and dose-dependently induce calcitonin gene-related peptide (CGRP) secretion; rhIL-2 alone does not effect hCGRP secretion, but it can potentiate PHA-evoked hCGRP secretion from human spleen lymphocytes. RPA shows that a- and b-CGRP mRNA is both constitutively expressed in unstimulated human peripheral blood mononuclear cells (PBMC). PHA can cause b-hCGRP but not a-hCGRP mRNA increase. hCGRP8-37, a CGRP1 receptor antagonist, enhances PHA or rhIL-2-induced the proliferation of splenocytes and PBMC. These results suggest that hCGRP is produced and secreted by human lymphocyte. Lymphocyte mitogen can induce the elevation of b-CGRP synthesis and secretion. The lymphocyte-derived b-CGRP may inhibit, at least in part, lymphocytes proliferation, which are then involved in the modulation of human T lymphocyte function in response to immune stimulation. In addition, IL-1b, a proinflammatory cytokine induces both CGRP release and synthesis that are mediated by both PKA-CREB and PKC-NF-kB pathways in human pulmonary epithelial cell worked as second immune tissue. The pulmonary epithelial cell-derived CGRP can inhibit IL-1b-induced chemokines, MCP-1 and IL-8 secretion. Here we provide another evidence for CGRP may act as a neuroendocrine immune modulator.

在前一已结题项目证明大鼠免疫细胞可合成和释放神经肽降钙素基因相关肽（CGRP）的基础上，拟研究人T淋巴细胞表达和释放CGRP的规律，特别当病人细胞免疫功能激活或抑制时，T细胞表达和释放CGRP的变化，以及上述变化对免疫细胞等功能的影响，以期揭示人免疫细胞合成和释放神经肽CGRP的临床意义。为寻找诊断和治疗新措施提供线索。