Centre de Recherche du CHU de Québec, Department of Microbiology, Infectiology & Immunology, Faculty of Medicine, Université Laval, Québec, Canada
* Corresponding author: Email: Marc.Pouliot@crchul.ulaval.ca
Expressed in response to injury or infection, tumour necrosis factor-alpha (TNF-α ) is a highly potent mediator of inflammation. Controlled expression of TNF-α is crucial, since overexpression can lead to autoimmune disease and tissue damage. TNF-α expression is regulated at different levels, including transcription, mRNA turnover and translation. Many reviews have focused on the signalling pathways that mediate cellular responses following TNF-α receptor engagement. In this article, we focus on an aspect that shows promise for pharmaceutical intervention, namely intracellular mechanisms regulating production of TNF-α in immune cells, especially post-transcriptional checkpoints. We discuss the roles of adenosine-uridine-rich-element-binding proteins, micro-RNA and MAP kinase in the post-transcriptional regulation of TNF-α mRNA activity and their relevance to the physiopathology of rheumatoid arthritis.
A better understanding of the intracellular proteins and signalling pathways that regulate TNF-α biosynthesis is crucial to the development of novel anti-TNF-based therapies for rheumatoid arthritis patients.