Role of Tristetraprolin in the Resolution of Inflammation.

Abstract

Simple SummaryChronic inflammatory diseases account for up to 60% of deaths worldwide and, thus, are considered a great threat for human health by the World Health Organization. Nevertheless, acute inflammatory reactions are an integral part of the host defense against invading pathogens or injuries. To avoid excessive damage due to the persistence of a highly reactive environment, inflammations need to resolve in a coordinate and timely manner, ensuring for the immunological normalization of the affected tissues. Since post-transcriptional regulatory mechanisms are essential for effective resolution, the present review discusses the key role of the RNA-binding and post-transcriptional regulatory protein tristetraprolin in establishing resolution of inflammation.Inflammation is a crucial part of immune responses towards invading pathogens or tissue damage. While inflammatory reactions are aimed at removing the triggering stimulus, it is important that these processes are terminated in a coordinate manner to prevent excessive tissue damage due to the highly reactive inflammatory environment. Initiation of inflammatory responses was proposed to be regulated predominantly at a transcriptional level, whereas post-transcriptional modes of regulation appear to be crucial for resolution of inflammation. The RNA-binding protein tristetraprolin (TTP) interacts with AU-rich elements in the 3′ untranslated region of mRNAs, recruits deadenylase complexes and thereby facilitates degradation of its targets. As TTP regulates the mRNA stability of numerous inflammatory mediators, it was put forward as a crucial post-transcriptional regulator of inflammation. Here, we summarize the current understanding of the function of TTP with a specific focus on its role in adding to resolution of inflammation.