克氏外科学炎症导论2白介素1.docxVIP

Similar to the other members of the IL-1 family, IL-1RA can be produced by a variety of cell types. However, unlike IL-1α and IL-1β, IL-1RA is synthesized with a leader peptide that allows normal secretion of the protein. A specialized form of IL-1RA, intracellular IL-1RA, is synthesized without a leader peptide sequence and therefore accumulates intracellularly in certain cell types. In some tissues, such as intestinal epithelium, the formation of intracellular IL-1RA may serve a counter-regulatory function to limit inflammation and thereby confer mucosal protection. Moreover, an imbalance between the production of IL-1 and IL-1RA may promote the development of chronic inflammation in certain pathologic conditions such as Crohns disease.[32] Cellular production of IL-1 and IL-1RA is differentially regulated. Certain cytokines, notably IL-4, IL-10, and IL-13, which function in many ways as counter-regulatory cytokines, serve as anti-inflammatory mediators, in part by promoting the synthesis of IL-1RA. IL-6, though not usually thought of as an anti-inflammatory cytokine, is also capable of triggering the production of IL-1RA.和 IL-1 家族的其他两种蛋白一样， IL-1 RA也可以由很多的细胞分泌。但是，不同于 IL-1 α和 IL-1 β的是， IL-1 RA在合成的时候带有一个前导信号肽，这个信号肽能够促使 IL-1 RA以一种正常的途径被运输到细胞外部。一些特殊类型的 IL-1 RA，比如说细胞内的 IL-1 RA，他们没有合成这个信号肽，因此常常可以在细胞内部大量的堆积。在一些组织当中，比如说肠上皮细胞，细胞内的 IL-1 RA大量堆积，能够起到一种反向调节的作用，从而完成抑制炎症反应，保护肠粘膜。 IL-1 和 IL-1 RA的不均衡可以促进一些慢性疾病的产生，比如说克罗恩疾病。细胞合成分泌 IL-1 和 IL-1 RA受很多因素的调节。一些细胞因子，通常指的是白介素4、10和13，他们能够作为一种反向调节细胞因子，起到抗炎的作用，他们抗炎的途径就是促使 IL-1 RA分泌得多一些。白介素6，尽管不是一种通常认为的抗炎的细胞因子，但是，也可以作为促使 IL-1 RA分泌的物质。The importance of IL-1β as a proinflammatory cytokine and IL-1RA as an anti-inflammatory cytokine is emphasized by experiments using transgenic mouse strains deficient in IL-1RA, IL-1α, IL-1β, or both IL-1α and IL-1β (double knockout mice).[33] In these studies, IL-1α knockout mice were able to mount a normal inflammatory response, whereas the IL-1β knockout animals manifested an impaired ability to mount a normal