Transcriptional regulation by poly(ADP-ribose) polymerase-1 during T cell activation.
BACKGROUND
Accumulating evidence suggests an important role for the enzyme poly(ADP-ribose) polymerase-1 (PARP-1) as an integral part of the gene expression regulatory machinery during development and in response to specific cellular signals. PARP-1 might modulate gene expression through its catalytic activity leading to poly(ADP-ribosyl)ation of nuclear proteins or by its physical association with relevant proteins. Recently, we have shown that PARP-1 is activated during T cell activation. However, the proposed role of PARP-1 in reprogramming T cell gene expression upon activation remains largely unexplored.


RESULTS
In the present study we use oligonucleotide microarray analysis to gain more insight into the role played by PARP-1 during the gene expression reprogramming that takes place in T cells upon activation with anti-CD3 stimulation alone, or in combination with anti-CD28 co-stimulation. We have identified several groups of genes with expression modulated by PARP-1. The expression of 129 early-response genes to anti-CD3 seems to be regulated by PARP-1 either in a positive (45 genes) or in a negative manner (84 genes). Likewise, in the presence of co-stimulation (anti-CD3 + anti-CD28 stimulation), the expression of 203 genes is also regulated by PARP-1 either up (173 genes) or down (30 genes). Interestingly, PARP-1 deficiency significantly alters expression of genes associated with the immune response such as chemokines and genes involved in the Th1/Th2 balance.


CONCLUSIONS
This study provides new insights into changes in gene expression mediated by PARP-1 upon T cell activation. Pathway analysis of PARP-1 as a nuclear signalling molecule in T cells would be of relevance for the future development of new therapeutic approaches targeting PARP-1 in the acquired immune response.
Saenz
Luis
L
Transplant Unit, Department of Surgery, University Hospital Virgen de Arrixaca, University of Murcia, Ciberehd, Murcia, Spain. txito3@hotmail.com
Lozano
Juan J
JJ
Valdor
Rut
R
Baroja-Mazo
Alberto
A
Ramirez
Pablo
P
Parrilla
Pascual
P
Aparicio
Pedro
P
Sumoy
Lauro
L
Yélamos
José
J
D000818:Animals; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic
D011948:Receptors, Antigen, T-Cell; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases