Abnormal regulation of pro-inflammatory cytokine and chemokine mediators can contribute to the excess inflammation characteristic of many autoimmune diseases, such as rheumatoid arthritis, psoriasis, Crohn's disease, type 1 diabetes, and many others. The tristetraprolin (TTP) family consists of a small group of related RNA-binding proteins that bind to preferred AU-rich binding sites within the 3′-untranslated regions of specific mRNAs to promote mRNA deadenylation and decay. TTP deficient mice develop a severe systemic inflammatory syndrome consisting of arthritis, myeloid hyperplasia, dermatitis, autoimmunity and cachexia, due at least in part to the excess accumulation of proinflammatory chemokine and cytokine mRNAs and their encoded proteins. To investigate the possibility that increased TTP expression or activity might have a beneficial effect on inflammatory diseases, at least two mouse models have been developed that provide proof of principle that increasing TTP activity can promote the decay of pro-inflammatory and other relevant transcripts, and decrease the severity of mouse models of inflammatory disease. Animal studies of this type are summarized here, and we briefly review the prospects for harnessing these insights for the development of TTP-based anti-inflammatory treatments in humans.

促炎细胞因子和趋化因子介质的异常调节可导致许多自身免疫性疾病的过度炎症特征，例如类风湿性关节炎、牛皮癣、克罗恩病、1 型糖尿病等。三四脯氨酸 (TTP) 家族由一小组相关的 RNA 结合蛋白组成，这些蛋白结合特定 mRNA 的 3'-非翻译区内首选的富含 AU 的结合位点，以促进 mRNA 去腺苷酸化和衰变。TTP 缺陷小鼠会发展出严重的全身性炎症综合征，包括关节炎、骨髓增生、皮炎、自身免疫和恶病质，至少部分是由于促炎趋化因子和细胞因子 mRNA 及其编码蛋白的过度积累。为了研究增加 TTP 表达或活性可能对炎症性疾病产生有益影响的可能性，至少开发了两种小鼠模型，这些模型提供了增加 TTP 活性可以促进促炎和其他相关转录物衰变的原理证据，并且降低炎症性疾病小鼠模型的严重程度。此处总结了此类动物研究，我们简要回顾了利用这些见解开发基于 TTP 的人类抗炎治疗的前景。