TY - JOUR
AU1 - Anderson, Paul
AU2 - Phillips, Kristine
AU3 - Stoecklin, Georg
AU4 - Kedersha, Nancy
AB - Post-transcriptional mechanisms play a critical role in regulating the expression of numerous proteins that promote inflammatory arthritis. The mRNAs encoding a subset of these proteins possess adenine/uridine-rich elements (AREs) in their 3′-untranslated regions that profoundly influence the rate at which mRNA is degraded and translated into protein. Tristetraprolin (TTP) and T cell intracellular antigen-1 (TIA-1) are ARE-binding proteins that dampen the expression of this class of proteins by promoting mRNA degradation and protein translation, respectively. We have discovered that TIA-1 and TTP function as arthritis-suppressor genes: TIA-1−/− mice develop mild arthritis, TTP−/− mice develop severe arthritis, and TIA-1−/−TTP−/− mice develop very severe arthritis. Paradoxically, lipopolysaccharide (LPS)-activated macrophages derived from TIA-1−/−TTP−/− macrophages produce less tumor necrosis factor α (TNF-α) than TIA-1−/− or TTP−/− macrophages. The bone marrows of these mice exhibit increased cellularity, reflecting the presence of mature neutrophils that secrete TNF-α in response to LPS stimulation. We hypothesize that TIA-1−/−TTP−/− neutrophils are a source of arthritigenic TNF-α, which promotes severe erosive arthritis in these mice.
TI - Post-transcriptional regulation of proinflammatory proteins
JF - Journal of Leukocyte Biology
DO - 10.1189/jlb.1103536
DA - 2004-04-01
UR - https://www.deepdyve.com/lp/oxford-university-press/post-transcriptional-regulation-of-proinflammatory-proteins-0FWzqxBPI2
SP - 42
EP - 47
VL - 76
IS - 1
DP - DeepDyve
ER -