tailieunhanh - Báo cáo y học: "Modulation of collagen-induced arthritis by adenovirus-mediated intra-articular expression of modified collagen type II"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài:Modulation of collagen-induced arthritis by adenovirus-mediated intra-articular expression of modified collagen type II. | Tang et al. Arthritis Research Therapy 2010 12 R136 http content 12 4 R136 RESEARCH ARTICLE Open Access Modulation of collagen-induced arthritis by adenovirus-mediated intra-articular expression of modified collagen type II Bo Tang1 David L Cullins1 Jing Zhou1 Janice A Zawaski2 Hyelee Park1 3 David D Brand1 4 Karen A Hasty3 M Waleed Gaber2 John M Stuart1 4 Andrew H Kang1 4 and Linda K Myers 5 Abstract Introduction Rheumatoid arthritis RA is a systemic disease manifested by chronic inflammation in multiple articular joints including the knees and small joints of the hands and feet. We have developed a unique modification to a clinically accepted method for delivering therapies directly to the synovium. Our therapy is based on our previous discovery of an analog peptide A9 with amino acid substitutions made at positions 260 I to A 261 A to B and 263 F to N that could profoundly suppress immunity to type II collagen CII and arthritis in the collagen-induced arthritis model CIA . Methods We engineered an adenoviral vector to contain the CB11 portion of recombinant type II collagen and used PCR to introduce point mutations at three sites within CII124-402 260A 261B 263D rCB11-A9 so that the resulting molecule contained the A9 sequence at the exact site of the wild-type sequence. Results We used this construct to target intra-articular tissues of mice and utilized the collagen-induced arthritis model to show that this treatment strategy provided a sustained local therapy for individual arthritic joints effective whether given to prevent arthritis or as a treatment. We also developed a novel system for in vivo bioimaging using the firefly luciferase reporter gene to allow serial bioluminescence imaging to show that luciferase can be detected as late as 18 days post injection into the joint. Conclusions Our therapy is unique in that we target synovial cells to ultimately shut down T cell-mediated inflammation. Its effectiveness is based on its .