Linked Life Data

16272356

Source:http://linkedlifedata.com/resource/pubmed/id/16272356

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2005-11-7
pubmed:abstractText
Systemic lupus erythematosus (SLE) is a progressive autoimmune disease characterized by the production of high levels of affinity-matured IgG autoantibodies to dsDNA and, possibly, visceral involvement. Pathogenic autoantibodies result from the activation and proliferation of autoreactive T and B lymphocytes stimulated by epitopes borne by nucleosomal histones. To inhibit the proliferation of autoreactive cells and abrogate the development of SLE, a novel tool, cell cycle inhibiting peptide therapy, was used. Thus, a peptidyl mimic of p21WAF1/CIP1 that inhibits the interaction between cyclin-dependent kinase 4 and type D cyclins abrogated the in vitro proliferative response of T cells to histones and T-independent and T-dependent proliferative responses of B cells. The WAF1/CIP1 mimic also abrogated the in vitro production of total and anti-dsDNA IgG Abs by B cells. Similarly, the p21WAF1/CIP1 construct inhibited the ex vivo T and B cell proliferative responses to histones and decreased the numbers of activated/memory B and T spleen cells. The alterations in the balance of spleen cell subsets resulted from proapoptotic effects of the p21WAF1/CIP1)construct on activated splenocytes. Finally, in vivo, four i.v. injections of the p21WAF1/CIP1 mimic were sufficient to inhibit the progression of the lupus-like syndrome in (NZB x NZW)F1 mice. The levels of anti-dsDNA IgG autoantibodies and the incidence and severity of renal involvement were lower in treated mice than in nontreated mice. Those observations open new avenues for the treatment of SLE and prompt us to evaluate the potential interest of peptidic therapy in human SLE.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
175
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6959-67
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16272356-Amino Acid Sequence, pubmed-meshheading:16272356-Animals, pubmed-meshheading:16272356-Antibodies, Antinuclear, pubmed-meshheading:16272356-Apoptosis, pubmed-meshheading:16272356-B-Lymphocytes, pubmed-meshheading:16272356-Cyclin D, pubmed-meshheading:16272356-Cyclin-Dependent Kinase 4, pubmed-meshheading:16272356-Cyclin-Dependent Kinase 6, pubmed-meshheading:16272356-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:16272356-Cyclins, pubmed-meshheading:16272356-Female, pubmed-meshheading:16272356-Humans, pubmed-meshheading:16272356-Lupus Erythematosus, Systemic, pubmed-meshheading:16272356-Lymphocyte Activation, pubmed-meshheading:16272356-Mice, pubmed-meshheading:16272356-Mice, Inbred NZB, pubmed-meshheading:16272356-Molecular Mimicry, pubmed-meshheading:16272356-Molecular Sequence Data, pubmed-meshheading:16272356-T-Lymphocytes
pubmed:year
2005
pubmed:articleTitle
A mimic of p21WAF1/CIP1 ameliorates murine lupus.
pubmed:affiliation
Laboratoire d'Immunologie, Faculté de Médecine René Descartes et Hôpital Cochin, Université Paris 5, Paris, France.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't