Tang H, Sun L, Xin Z, Ganea D
Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102, USA.
Ann N Y Acad Sci. 1996 Dec 26;805:768-78. doi: 10.1111/j.1749-6632.1996.tb17555.x.
Neuropeptides, such as VIP and PACAP, released or produced in the microenvironment of the primary and secondary lymphoid organs, could affect a variety of immune responses through the regulation of cytokine expression. VIP has been previously shown to inhibit IL-2, IL-4, and IL-10 production in murine lymphocytes stimulated through the TCR-associated CD3 complex. This study shows that, similar to VIP, PACAP-38 inhibits IL-2 production in T lymphocytes. Comparisons with forskolin, a known cAMP inducer, suggest that the increase in intracellular cAMP represents at least one of the transduction pathways involved in IL-2 inhibition, especially in the higher range of neuropeptide concentration. Studies of the detailed molecular mechanisms involved in the regulation of IL-2 expression indicate that reduction of de novo transcription and destabilization of the message contribute to the reduction of steady-state IL-2 mRNA levels following VIP treatment. Examination of several IL-2 transcriptional factors indicates that only NFAT is down-regulated by VIP. Neuropeptides, such as VIP and PACAP, which specifically modulate the expression of various cytokines, could play an important role in the intricate cytokine network controlling local immune responses.
在一级和二级淋巴器官微环境中释放或产生的神经肽，如血管活性肠肽（VIP）和垂体腺苷酸环化酶激活肽（PACAP），可通过调节细胞因子表达来影响多种免疫反应。此前已有研究表明，VIP可抑制通过TCR相关CD3复合物刺激的小鼠淋巴细胞中IL-2、IL-4和IL-10的产生。本研究表明，与VIP类似，PACAP-38也可抑制T淋巴细胞中IL-2的产生。与已知的cAMP诱导剂毛喉素进行比较表明，细胞内cAMP的增加至少代表了参与IL-2抑制的转导途径之一，尤其是在较高浓度的神经肽范围内。对IL-2表达调控所涉及的详细分子机制的研究表明，VIP处理后，从头转录的减少和信使RNA的不稳定导致了稳态IL-2 mRNA水平的降低。对几种IL-2转录因子的检测表明，只有活化T细胞核因子（NFAT）受VIP下调。诸如VIP和PACAP等能够特异性调节各种细胞因子表达的神经肽，可能在控制局部免疫反应的复杂细胞因子网络中发挥重要作用。
