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Regulation and localization of endogenous human tristetraprolin

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Year: 2003, Volume: 5, Issue: 3

Year: 2003, Volume: 5, Issue: 2

Year: 2003, Volume: 5, Issue: 1

Year: 2002, Volume: 5

Regulation and localization of endogenous human tristetraprolin

Content Provider	PubMed Central
Author	Fairhurst, Anna-marie Connolly, John E. Hintz, Katharine A. Goulding, Nicolas J. Rassias, Athos J. Yeager, Mark P. Rigby, William Wallace, Paul K.
Abstract	Tumor necrosis factor (TNF) has been implicated in the development and pathogenicity of infectious diseases and autoimmune disorders, such as septic shock and arthritis. The zinc-finger protein tristetraprolin (TTP) has been identified as a major regulator of TNF biosynthesis. To define its intracellular location and examine its regulation of TNF, a quantitive intracellular staining assay specific for TTP was developed. We establish for the first time that in peripheral blood leukocytes, expression of endogenous TTP is confined to the cytoplasm. Baseline expression of TTP was higher in monocytes than in lymphocytes or neutrophils. After in vitro incubation with lipopolysaccharide (LPS), leukocyte TTP levels increased rapidly, peaking after approximately 2 hours. Monocytes showed the greatest response to LPS stimulation and lymphocytes the least. TTP levels were also studied in leukocytes isolated from healthy volunteers infused with a bolus dose of LPS. TTP expression and initial upregulation in response to LPS infusion were consistent with the in vitro data. Neutrophil TTP levels responded first, reaching an initial peak within 1 hour, monocyte levels peaked next at 2 hours, followed by lymphocytes at 4 hours. This response paralleled plasma TNF levels, which peaked 2 hours after infusion and were no longer detectable after 12 hours. A second rise in intracellular TTP levels, which did not parallel plasma TNF levels, was observed in all leukocyte populations, starting 12 hours after infusion. These data establish the cytoplasmic location of TTP, supporting a major role for this protein in regulating TNF production, and suggest that TTP levels are not regulated solely by TNF.
Related Links	http://dx.doi.org/10.1186/ar778
Starting Page	214
File Format	PDF
ISSN	14659905
e-ISSN	14786362
Journal	Arthritis Research & Therapy
Issue Number	4
Volume Number	5
Language	English
Publisher	BioMed Central
Publisher Date	2003-01-01
Access Restriction	Open
Rights Holder	BioMed Central
Subject Keyword	Rheumatology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Rheumatology

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