Enhanced stability of tristetraprolin mRNA protects mice against immune-mediated inflammatory pathologies
Abstract
Inflammation is involved in the pathogenesis of many chronic diseases. Many deleterious effects of inflammation are mediated through increased production of proinflammatory mediators, known as cytokines and chemokines. Many current therapies for these diseases involve blocking single proinflammatory mediators, such as TNF, using parenteral administration of recombinant binding proteins. We demonstrate here that a genetic modification in the mouse that increases the expression of an endogenous antiinflammatory protein, tristetraprolin (TTP), results in protection against mouse models for several human inflammatory diseases, including rheumatoid arthritis, psoriasis, and multiple sclerosis, presumably by decreasing the production of proinflammatory cytokines. Our results suggest that increasing TTP expression may be an effective therapeutic strategy in the treatment of certain inflammatory diseases.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- February 2016
- DOI:
- 10.1073/pnas.1519906113
- Bibcode:
- 2016PNAS..113.1865P