Dual Effects of IL-1 Overactivity on the Immune System in a Mouse Model of Arthritis due to Deficiency of IL-1 Receptor Antagonist  

作　　者：Jian Yan Yan Jiao Hong Chen Feng Jiao Karen A.Hasty John M.Stuart Weikuan Gu 

机构地区：[1]Department of Medicine,University of Tennessee Health Science Center [2]Department of Orthopedic Surgery and BME,University of Tennessee Health Science Center [3]Mudanjiang Medical College [4]The First Hospital of Qiqihaer City [5]Department of Veterans Affairs Medical Center

出　　处：《Journal of Genetics and Genomics》2013年第2期83-91,共9页遗传学报（英文版）

基　　金：supported by the Center of Genomics and Bioinformatics and Center of Connective Tissue Research at the University of Tennessee Health Science Center;Veterans Administration Medical Center in Memphis;National Institute of Arthritis and Musculoskeletal and Skin Diseases;National Institutes of Health(Nos.R01 AR51190 to W.G.and R01 AR50785 to J.S.)

摘　　要：Previous studies have revealed the significance of cytokine interleukin 1 （IL-1） in the onset and progression of rheumatoid arthritis （RA）. The precise molecular mechanisms related to IL-1 underlying RA is still elusive. We conducted a whole genome-wide tran- scriptomal comparison of wild-type （WT） and arthritis-prone IL-1 receptor antagonist （IL-lrn） deficient BALB/c mice to address this issue. To refine our search efforts, gene expression profiling was also performed on paired wild-type and arthritis-resistant IL-lrn deficient DBA/1 mice as internal controls when identifying causative arthritis candidate genes. Two hundred and fifteen transcripts were found to be dysregulated greater than or equal to 2-fold in the diseased mice. The altered transcriptome in BALB/c mice revealed increased myeloid cell activities and impaired lymphocyte functionality, suggesting dual regulatory effects of IL-1 hyperactivity on immunological changes associated with arthritis development. Phase-specific gene expression changes were identified, such as early increase and late decrease of heat shock protein coding genes. Moreover, common gene expression changes were also observed, especially the upregulation of paired Ig-like receptor A （Pira） in both early and late phases of arthritis. Real-time PCR was performed to validate the expression of Pira and an intervention experiment with a major histocompatibility complex （MHC） class I inhibitor （brefeldin A） was carded out to investigate the role of suppressing Pira activity. We conclude that global pattern changes of common and distinct gene expressions may represent novel opportunities for better control of RA through early diagnosis and development of alternative therapeutic strategies.Previous studies have revealed the significance of cytokine interleukin 1 （IL-1） in the onset and progression of rheumatoid arthritis （RA）. The precise molecular mechanisms related to IL-1 underlying RA is still elusive. We conducted a whole genome-wide tran- scriptomal comparison of wild-type （WT） and arthritis-prone IL-1 receptor antagonist （IL-lrn） deficient BALB/c mice to address this issue. To refine our search efforts, gene expression profiling was also performed on paired wild-type and arthritis-resistant IL-lrn deficient DBA/1 mice as internal controls when identifying causative arthritis candidate genes. Two hundred and fifteen transcripts were found to be dysregulated greater than or equal to 2-fold in the diseased mice. The altered transcriptome in BALB/c mice revealed increased myeloid cell activities and impaired lymphocyte functionality, suggesting dual regulatory effects of IL-1 hyperactivity on immunological changes associated with arthritis development. Phase-specific gene expression changes were identified, such as early increase and late decrease of heat shock protein coding genes. Moreover, common gene expression changes were also observed, especially the upregulation of paired Ig-like receptor A （Pira） in both early and late phases of arthritis. Real-time PCR was performed to validate the expression of Pira and an intervention experiment with a major histocompatibility complex （MHC） class I inhibitor （brefeldin A） was carded out to investigate the role of suppressing Pira activity. We conclude that global pattern changes of common and distinct gene expressions may represent novel opportunities for better control of RA through early diagnosis and development of alternative therapeutic strategies.

关 键 词：ARTHRITIS Gene expression MOUSE TRANSCRIPTOME 

分 类 号：R392[医药卫生—免疫学]