A potential role of myeloid DAP12-associating lectin (MDL)-1 in the regulation of inflammation in rheumatoid arthritis patients.
The pathogenic roles of myeloid DAP12-associating lectin-1(MDL-1) and DAP12 in human rheumatoid arthritis (RA) remain unknown. Frequencies of MDL-1-expressing monocytes in 22 active RA patients, 16 inactive RA patients, 12 osteoarthritis (OA) patients and 10 healthy controls (HC) were determined by flow-cytometry analysis. The mRNA expression levels of MDL-1 and DAP12 on PBMCs were evaluated by quantitative PCR, and their protein expression levels in the synovium were examined by immunohistochemistry. Significantly higher median percentages of circulating MDL-1-expressing monocytes were observed in active RA patients (53.6%) compared to inactive RA patients (34.1%), OA patients (27.9%), and HC (21.2%). Levels of MDL-1 and DAP12 gene expression in PBMCs and their protein expression in the synovium were significantly higher in active RA patients than in inactive RA or OA patients. MDL-1 levels were positively correlated with parameters of disease activity, articular damage, and levels of proinflammatory cytokines. MDL-1 activator (Dengue virus type 2 antigen) stimulation on PBMCs resulted in significantly enhanced levels of proinflammatory cytokines in RA patients compared to those in OA patients or HC, indicating that MDL-1 activation is functional. Frequencies of MDL-1-expressing monocytes and levels of MDL-1 and DAP12 gene expression significantly decreased after effective therapy. Concordant overexpression of MDL-1 and DAP12 were correlated with increased production of proinflammatory cytokines in RA patients, suggesting their roles in regulating articular inflammation.
Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C. ; Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C. ; Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan, R.O.C. ; Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, R.O.C. ; Infection and Immunity Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C.
Der-Yuan
DY
Chen
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.
Ling
L
Yao
Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C. ; Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.
Yi-Ming
YM
Chen
Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan, R.O.C.
Chi-Chen
CC
Lin
Department of Orthopedics and Traumatology, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.
Kui-Chou
KC
Huang
Infection and Immunity Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C.
Szu-Ting
ST
Chen
Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C. ; Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C. ; Division of Immunology and Rheumatology, China Medical University Hospital, Taichung, Taiwan, R.O.C. ; College of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
Joung-Liang
JL
Lan
Infection and Immunity Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C. ; Institute of Clinical Medicine, National Yang-Ming University, Taipei City, Taiwan.
Shie-Liang Edmond
SL
Hsieh
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood; D007596:Joints / Q000473:pathology; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; C509771:CLEC5A protein, human; D016207:Cytokines; D018836:Inflammation Mediators; D037181:Lectins, C-Type; D008565:Membrane Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C110546:TYROBP protein, human; D002097:C-Reactive Protein