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Updated: Aug 24, 2026

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Post-transcriptional regulation of proinflammatory proteins
Paul Anderson1, Kristine Phillips, Georg Stoecklin
1Immunology and Allergy, Brigham and Women's Hospital, Smith 652, One Jimmy Fund Way, Boston, MA 02115, USA. panderson@rics.bwh.harvard.edu
Abstract:
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 alpha (TNF-alpha) than TIA-1-/- or TTP-/- macrophages. The bone marrows of these mice exhibit increased cellularity, reflecting the presence of mature neutrophils that secrete TNF-alpha in response to LPS stimulation. We hypothesize that TIA-1-/-TTP-/- neutrophils are a source of arthritigenic TNF-alpha, which promotes severe erosive arthritis in these mice.
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