Anti-DR5 mAb ameliorate adjuvant arthritis rats through inducing synovial cells apoptosis
Study the therapeutic effects and immunoregulatory mechanisms of anti-DR5 mAb on adjuvant arthritis (AA) rats. AA rats induced by CFA, were treated with anti-DR5 mAb through mainline administration. Effect on the synovial membranes of the tissues was detected by H&E staining. Flow cytometry and...
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Published in | Experimental biology and medicine (Maywood, N.J.) Vol. 234; no. 12; p. 1468 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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England
01.12.2009
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Abstract | Study the therapeutic effects and immunoregulatory mechanisms of anti-DR5 mAb on adjuvant arthritis (AA) rats.
AA rats induced by CFA, were treated with anti-DR5 mAb through mainline administration. Effect on the synovial membranes of the tissues was detected by H&E staining. Flow cytometry and MTT assay were used for detecting the induced apoptosis in an in vitro system and TUNEL assay was used for analysis in an in vivo system. The involvement of the apoptotic pathway was further proved by a caspase inhibition assay.
Anti-DR5 mAb could induce synovial cell apoptosis in an in vitro system, which was related with the mRNA expression of DR5 on the cell surface. The mRNA expressions of c-myc and bcl-2 were decreased in synovial cells and those of p21, p53, and bax were increased. The protein expressions of caspase-8/3/9, RANKL, JNK2, and c-Jun were raised and that of bcl-2 was decreased. When the caspase inhibitor was added to the synovial cells treated with anti-DR5 mAb, it showed a dose-dependence inhibition effect, indicating that anti-DR5 mAb inducing apoptosis might be through the caspase pathway.
This study shows that anti-DR5 mAb can ameliorate arthritic symptoms. The mechanisms of the treatment are related to the increase in synovial cell apoptosis by regulating the mRNA expression of DR5 and apoptosis-related genes, prolonging the duration of the cell cycle by modulation of the mRNA expression of cell cycle-related genes, and the protein expression of the molecules in the caspase pathway and RANKL, JNK2, and c-Jun. |
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AbstractList | Study the therapeutic effects and immunoregulatory mechanisms of anti-DR5 mAb on adjuvant arthritis (AA) rats.
AA rats induced by CFA, were treated with anti-DR5 mAb through mainline administration. Effect on the synovial membranes of the tissues was detected by H&E staining. Flow cytometry and MTT assay were used for detecting the induced apoptosis in an in vitro system and TUNEL assay was used for analysis in an in vivo system. The involvement of the apoptotic pathway was further proved by a caspase inhibition assay.
Anti-DR5 mAb could induce synovial cell apoptosis in an in vitro system, which was related with the mRNA expression of DR5 on the cell surface. The mRNA expressions of c-myc and bcl-2 were decreased in synovial cells and those of p21, p53, and bax were increased. The protein expressions of caspase-8/3/9, RANKL, JNK2, and c-Jun were raised and that of bcl-2 was decreased. When the caspase inhibitor was added to the synovial cells treated with anti-DR5 mAb, it showed a dose-dependence inhibition effect, indicating that anti-DR5 mAb inducing apoptosis might be through the caspase pathway.
This study shows that anti-DR5 mAb can ameliorate arthritic symptoms. The mechanisms of the treatment are related to the increase in synovial cell apoptosis by regulating the mRNA expression of DR5 and apoptosis-related genes, prolonging the duration of the cell cycle by modulation of the mRNA expression of cell cycle-related genes, and the protein expression of the molecules in the caspase pathway and RANKL, JNK2, and c-Jun. |
Author | Zhang, Jiakai Liu, Zhongchen Yin, Ping Li, Wenzhu Hu, Qingzhong Zhuang, Guohong Tao, Huiran Qiu, Jinghua |
Author_xml | – sequence: 1 givenname: Wenzhu surname: Li fullname: Li, Wenzhu organization: Anti-Cancer Research Center, Medical College, Xiamen University, 422 SiMing South Road, Xiamen 361005, Fujian, China – sequence: 2 givenname: Zhongchen surname: Liu fullname: Liu, Zhongchen – sequence: 3 givenname: Guohong surname: Zhuang fullname: Zhuang, Guohong – sequence: 4 givenname: Ping surname: Yin fullname: Yin, Ping – sequence: 5 givenname: Huiran surname: Tao fullname: Tao, Huiran – sequence: 6 givenname: Jinghua surname: Qiu fullname: Qiu, Jinghua – sequence: 7 givenname: Qingzhong surname: Hu fullname: Hu, Qingzhong – sequence: 8 givenname: Jiakai surname: Zhang fullname: Zhang, Jiakai |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19934367$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1016_j_bcp_2011_12_036 crossref_primary_10_1016_j_intimp_2020_106418 crossref_primary_10_1155_2015_564042 crossref_primary_10_1002_art_33492 crossref_primary_10_1089_mab_2015_0030 crossref_primary_10_3892_mmr_2017_7311 |
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Snippet | Study the therapeutic effects and immunoregulatory mechanisms of anti-DR5 mAb on adjuvant arthritis (AA) rats.
AA rats induced by CFA, were treated with... |
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SubjectTerms | Animals Antibodies, Monoclonal - immunology Antibodies, Monoclonal - pharmacology Apoptosis - drug effects Apoptosis - immunology Arthritis, Experimental - chemically induced Arthritis, Experimental - drug therapy Arthritis, Experimental - immunology Arthritis, Experimental - metabolism bcl-2-Associated X Protein - biosynthesis bcl-2-Associated X Protein - immunology Caspases - biosynthesis Caspases - immunology Gene Expression Regulation - drug effects Gene Expression Regulation - immunology Genes, myc - immunology Male Mitogen-Activated Protein Kinase 9 - biosynthesis Mitogen-Activated Protein Kinase 9 - immunology Proto-Oncogene Proteins c-jun - biosynthesis Proto-Oncogene Proteins c-jun - immunology RANK Ligand - biosynthesis RANK Ligand - immunology Rats Rats, Sprague-Dawley Receptors, TNF-Related Apoptosis-Inducing Ligand - biosynthesis Receptors, TNF-Related Apoptosis-Inducing Ligand - immunology Synovial Fluid - immunology Synovial Fluid - metabolism Tumor Suppressor Protein p53 - biosynthesis Tumor Suppressor Protein p53 - immunology |
Title | Anti-DR5 mAb ameliorate adjuvant arthritis rats through inducing synovial cells apoptosis |
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