Protein Phosphatase 2A is a Negative Regulator of IL-2 Production in Patients with Systemic Lupus Erythematosus

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2005 Oct 15

PMID 16224536

Citations 86

Authors

Christina G Katsiari

Vasileios C Kyttaris

Yuang-Taung Juang

George C Tsokos

Affiliations

Soon will be listed here.

Abstract

Decreased IL-2 production in systemic lupus erythematosus (SLE) represents a central component of the disease immunopathology. We report that the message, protein, and enzymatic activity of the catalytic subunit of protein phosphatase 2A (PP2Ac), but not PP1, are increased in patients with SLE regardless of disease activity and treatment and in a disease-specific manner. Treatment of SLE T cells with PP2Ac-siRNA decreased the protein levels and activity of PP2Ac in a specific manner and increased the levels of phosphorylated cAMP response element-binding protein and its binding to the IL2 and c-fos promoters, as well as increased activator protein 1 activity, causing normalization of IL-2 production. Our data document increased activity of PP2A as a novel SLE disease-specific abnormality and define a distinct mechanism whereby it represses IL-2 production. We propose the use of PP2Ac-siRNA as a novel tool to correct T cell IL-2 production in SLE patients.

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