Gomariz R P, Juarranz Y, Abad C, Arranz A, Leceta J, Martinez C
Department of Cell Biology, Faculty of Biology, Complutense University, 28040 Madrid, Spain.
Ann N Y Acad Sci. 2006 Jul;1070:51-74. doi: 10.1196/annals.1317.031.
Our research about VIP/PACAP and the immune system goes back to 1990 when our group described the expression of VIP on lymphocytes for the first time. Since this year, using three models of disease, septic shock, rheumathoid arthritis, and Crohn's disease, we are trying to contribute with new pieces to the puzzle of immunity to approach the use of VIP/PACAP system as a therapeutic agent. In 1999 we established that the first step in the beneficial effect of the VIP/PACAP system exerts consists in its potent anti-inflammatory action. Thus, VIP and PACAP inhibit the expression and release of proinflammatory cytokines and chemokines, and enhance the production of the anti-inflammatory factors. These effects were reported both in vitro and in vivo, are mediated by the presence of PAC1, VPAC1, and VPAC2 receptors, in the three models of diseases used. The next step was that the system favors Th2 responses versus Th1 contributing to the remission of illness as rheumatoid arthritis or Crohn's disease by blocking the autoimmune component of these diseases. Because it appears that inflammatory processes requires more than blockade of a single mediator, new therapies blocking several components of both the infection- and the autoimmunity-induced inflammation cascades should be an interesting focus of attention. In this sense, at present we are trying to dissect new aspects of the potential therapeutic of the VIP/PACAP system in the control of CC and CXC chemokine and their receptors, coagulation factors, adhesion molecules, acute phase proteins, and osteoclastogenesis mediators as well as in the modulation of the expression of Toll-like receptors. Our more recent data open a hopeful door for the therapeutic use of VIP/PACAP in humans.
我们关于血管活性肠肽（VIP）/垂体腺苷酸环化酶激活肽（PACAP）与免疫系统的研究可追溯到1990年，当时我们团队首次描述了VIP在淋巴细胞上的表达。从那一年起，我们利用三种疾病模型，即脓毒症休克、类风湿性关节炎和克罗恩病，试图为免疫难题增添新的内容，以探讨将VIP/PACAP系统用作治疗药物的可能性。1999年我们确定，VIP/PACAP系统发挥有益作用的第一步在于其强大的抗炎作用。因此，VIP和PACAP可抑制促炎细胞因子和趋化因子的表达与释放，并增强抗炎因子的产生。这些效应在体外和体内均有报道，在所使用的三种疾病模型中，它们是由PAC1、VPAC1和VPAC2受体介导的。下一步是该系统有利于Th2反应而非Th1反应，通过阻断类风湿性关节炎或克罗恩病等疾病的自身免疫成分，促进疾病缓解。因为似乎炎症过程需要阻断的不仅仅是单一介质，所以阻断感染和自身免疫诱导的炎症级联反应多个成分的新疗法应该是一个有趣的关注焦点。从这个意义上说，目前我们正试图剖析VIP/PACAP系统在控制CC和CXC趋化因子及其受体、凝血因子、黏附分子、急性期蛋白和破骨细胞生成介质方面潜在治疗作用的新方面，以及在调节Toll样受体表达方面的作用。我们最近的数据为VIP/PACAP在人类治疗中的应用打开了一扇充满希望的大门。
