Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes
Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes
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DOI：
10.1172/jci13416
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发表时间：
2001-07-01
影响因子：
15.9
通讯作者：
Koller, BH
中科院分区：
文献类型：
--
作者：
Tilley, SL;Coffman, TM;Koller, BH
TPA，十四烷酰基佛波醇乙酸酯。在急性炎症中，在白细胞募集之前立即发生。随着免疫细胞浸润组织，观察到前列腺素水平的进一步增加。产生的前列腺素类的概况也可以在反应过程中显著变化。例如，在角叉菜胶诱导的胸膜炎模型中，仅在炎症的早期阶段观察到升高的PGE 2水平，而在反应的最后阶段PGD 2变得明显（1）。前列腺素类的产生取决于细胞内两种考克斯同工酶的活性。考克斯-1存在于大多数细胞中，并且其表达通常是组成型的。相反，考克斯-2在大多数细胞中表达较低或检测不到，但其表达在刺激后显著增加，特别是在免疫系统细胞中（2）。白细胞的募集和炎症刺激物诱导考克斯-2表达可能解释了慢性炎性病变中发现的高水平的前列腺素，并为开发治疗关节炎和其他慢性炎性疾病的考克斯-2特异性抑制剂提供了合理的基础。然而，考克斯-1调节炎症反应的能力不应被忽视。对暴露于LPS后的循环单核细胞的研究表明，考克斯-1表达在活化后会发生一些增加（3）。此外，使用考克斯-1或考克斯-2表达缺陷的小鼠的研究已经确定了考克斯-1在某些炎症反应的起始中的独特作用（表1）。在肥大细胞中，Reddy及其同事发现，在刺激的前30分钟内，PGD 2的产生几乎完全取决于考克斯-1。虽然考克斯-1也有助于PGD 2的产生，
TPA, tetradecanoyl phorbol acetate. immediately in acute inflammation prior to the recruitment of leukocytes. As immune cells infiltrate the tissues, further increases in prostanoid levels are observed. The profile of prostanoids that are produced can also vary dramatically during the course of the response. For example, in the carrageenan-induced pleurisy model, elevated PGE2 levels are observed only during the early stages of inflammation, whereas PGD2 becomes pronounced during the final stages of the response (1).Prostanoid production depends on the activity of the two COX isoenzymes within cells. COX-1 is present in most cells and its expression is generally constitutive. In contrast, COX-2 expression is low or undetectable in most cells but its expression increases dramatically upon stimulation, particularly in cells of the immune system (2). The recruitment of leukocytes and the induction of COX-2 expression by inflammatory stimuli likely account for the high levels of prostanoids found in chronic inflammatory lesions and provided a rational basis for the development of COX-2–specific inhibitors for treating arthritis and other chronic inflammatory diseases. However, the capacity for COX-1 to modulate inflammatory responses should not be overlooked. Studies of circulating monocytes after exposure to LPS suggest that some increases in COX-1 expression can occur upon activation (3). In addition, studies using mice deficient in the expression of COX-1 or COX-2 have identified unique roles for COX-1 in the initiation of certain inflammatory responses (Table 1). In mast cells, Reddy and associates found that the production of PGD2 within the first 30 minutes of stimulation depends almost entirely on COX-1. While COX-1 also contributes to the production of PGD2 by