NEW YORK (Reuters Health) - Levels of the tumor suppressor protein p53 are reduced in lymphocytes of patients with rheumatoid arthritis (RA), making the cells less likely to undergo apoptosis, investigators report in the April issue of Arthritis and Rheumatism.
“We have previously done microarray analysis looking for genes that are differentially expressed in autoimmune disease versus normals,” senior author Dr. Thomas Aune told Reuters Health. “p53 was one of the genes highly underexpressed in the rheumatoid arthritis population.”
When Dr. Aune’s group exposed peripheral blood mononuclear cells to gamma radiation, those from patients with RA were less likely to undergo apoptosis. However, RA cells were similar to control cells in their response to p53-independent modes of apoptosis, including dexamethasone, staurosporine and UV radiation.
Baseline levels of p53 were > 10-fold lower in RA cells, and gamma radiation exposure was associated with a reduced or absent increase in p53 levels in RA cells. Downstream p53 apoptotic effector function was also compromised in RA cells, as demonstrated by lower induction of PUMA (p45 up-regulated modulator of apoptosis) and PARP-1 (poly(ADP-ribose) polymerase 1) cleavage.
Microarray analysis showed that genes overexpressed in p53-positive cell lines were underexpressed in those from RA patients, and conversely, genes underexpressed in p53-positive cell lines were overexpressed in RA.
These effects may explain the increased risk of lymphoma in RA patients, Dr. Aune noted.
Effects on p53 are not limited to RA. “We also see low p53 in other autoimmune diseases,” such as multiple sclerosis, he said.
His group’s next steps will be to “see how do the defects in gene expression of these specific genes contribute to the development of autoimmunity. That may help us understand better ways to intervene” in autoimmune disease, he added.
Source: Arthritis Rheum 2005;52:1047-1057. [ Google search on this article ]
MeSH Headings:DNA-Binding Proteins: Genetic Techniques: Investigative Techniques: Nuclear Proteins: Phosphoproteins: Genes, p53: Protein p53: Gene Expression Profiling: Analytical, Diagnostic and Therapeutic Techniques and EquipmentCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
