Post-transcriptional regulation of tumour necrosis factor alpha biosynthesis: Relevance to the pathophysiology of rheumatoid arthritis

Abstract

Expressed in response to injury or infection, tumour necrosis factor- alpha (TNF-α) is a highly potent me- diator of inflammation. Controlled expression of TNF-α is crucial, since overexpression can lead to autoim- mune disease and tissue damage. TNF-α expression is regulated at different levels, including transcrip- tion, mRNA turnover and transla- tion. Many reviews have focused on the signalling pathways that medi- ate 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 pro- teins, micro-RNA and MAP kinase in the post-transcriptional regulation of TNF-α mRNA activity and their relevance to the physiopathology of rheumatoid arthritis.