PUMA-mediated apoptosis in fibroblast-like synoviocytes does not require p53 英文参考文献.docVIP

Available online /content/8/6/R157 Research article Open Access Vol 8 No 6 PUMA-mediated apoptosis in fibroblast-like synoviocytes does not require p53 Xin You, David L Boyle, Deepa Hammaker and Gary S Firestein Division of Rheumatology, Allergy and Immunology, University of California at San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California 92093, USA Corresponding author: Gary S Firestein, gfirestein@ Received: 5 Jul 2006 Revisions requested: 14 Aug 2006 Revisions received: 13 Sep 2006 Accepted: 2 Oct 2006 Published: 2 Oct 2006 Arthritis Research Therapy 2006, 8:R157 (doi:10.1186/ar2052) This article is online at: /content/8/6/R157 ? 2006 You et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract PUMA (p53-upregulated modulator of apoptosis) is a pro- apoptotic gene that can induce rapid cell death through a p53- dependent mechanism. However, the efficacy of PUMA gene therapy to induce synovial apoptosis in rheumatoid arthritis might have limited efficacy if p53 expression or function is deficient. To evaluate this issue, studies were performed to measure histone release and caspase-3 activation, or by trypan blue dye exclusion to measure cell viability. Initial studies showed that p53 siRNA decreased p53 expression by more than 98% in human FLS. Loss of p53 increased the growth rate of cells and suppressed p21 expression. However, PUMA still induced apoptosis in control and p53-deficient FLS after PUMA cDNA transfection. Similar results were observed in p53-/- determine whether p53 is required for PUMA-mediated apoptosis in fibroblast-like synoviocytes (FLS). p53 protein was depleted or inhibited in human FLS by using p53 siRNA or