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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2010-7-14
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pubmed:abstractText |
Main features of rheumatoid arthritis (RA), hyperplasia of fibroblast-like synoviocytes (FLS) and joint destruction are caused by inflammatory cytokines produced in chronic autoimmune inflammation. Cell-intrinsic acquisition of tumour-like phenotypes of RA-FLS could also be responsible for the aggressive proliferation and invasion, which are supported by the fact that in some cases RA-FLS has mutations of a tumour suppressor gene TP53. However, the underlying molecular mechanism for TP53 mutations in RA-FLS has not yet been clarified. Recently it has been reported that the non-lymphoid cells in the inflammatory tissues express ectopically the activation-induced cytidine deaminase (AID) gene that induces somatic hypermutations, not only at the immunoglobulin (Ig) gene variable regions in germinal centre B lymphocytes but also at coding regions in TP53. Real-time polymerase chain reaction (PCR) analyses revealed more than half (five of nine) of the RA-FLS lines we established showed the markedly increased expression of AID. AID transcription in RA-FLS was augmented by tumour necrosis factor (TNF)-alpha and even by physiological concentration of beta-oestradiol that could not induce AID transcription in osteoarthritis-FLS. Furthermore, AID-positive RA-FLS presented a higher frequency of somatic mutations in TP53. Cytological and immunohistochemical analyses demonstrated clearly the ectopic expression of AID in the FLS at the RA synovium. These data suggested strongly a novel consequence of RA; the ectopic expression of AID in RA-FLS causes the somatic mutations and dysfunction of TP53, leading to acquisition of tumour-like properties by RA-FLS.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20491788-10366100,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20491788-10446856,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20491788-10568429,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20491788-11219390,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20491788-12748655,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20491788-15108353,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20491788-15189732,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20491788-18982160,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20491788-8654922,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20491788-8717520,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20491788-9380731,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20491788-9486403
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1365-2249
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
161
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
71-80
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:20491788-Aged,
pubmed-meshheading:20491788-Aged, 80 and over,
pubmed-meshheading:20491788-Arthritis, Rheumatoid,
pubmed-meshheading:20491788-Cell Line, Transformed,
pubmed-meshheading:20491788-Cell Transformation, Neoplastic,
pubmed-meshheading:20491788-Computer Systems,
pubmed-meshheading:20491788-Cytidine Deaminase,
pubmed-meshheading:20491788-Enzyme Induction,
pubmed-meshheading:20491788-Estradiol,
pubmed-meshheading:20491788-Female,
pubmed-meshheading:20491788-Gene Expression Regulation,
pubmed-meshheading:20491788-Genes, p53,
pubmed-meshheading:20491788-Humans,
pubmed-meshheading:20491788-Hyperplasia,
pubmed-meshheading:20491788-Male,
pubmed-meshheading:20491788-Middle Aged,
pubmed-meshheading:20491788-Mutation,
pubmed-meshheading:20491788-Osteoarthritis,
pubmed-meshheading:20491788-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20491788-Synovial Membrane,
pubmed-meshheading:20491788-Transcription, Genetic,
pubmed-meshheading:20491788-Tumor Necrosis Factor-alpha,
pubmed-meshheading:20491788-Tumor Suppressor Protein p53
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pubmed:year |
2010
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pubmed:articleTitle |
TP53 mutations coincide with the ectopic expression of activation-induced cytidine deaminase in the fibroblast-like synoviocytes derived from a fraction of patients with rheumatoid arthritis.
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