Role of Macrophage CCAATEnhancer Binding Protein Delta in the Pathogenesis of Rheumatoid Arthritis in Collagen-Induced Arthritic Mice 英文参考文献.docVIP

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Role of Macrophage CCAATEnhancer Binding Protein Delta in the Pathogenesis of Rheumatoid Arthritis in Collagen-Induced Arthritic Mice 英文参考文献.doc

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Role of Macrophage CCAATEnhancer Binding Protein Delta in the Pathogenesis of Rheumatoid Arthritis in Collagen-Induced Arthritic Mice 英文参考文献

RoleofMacrophageCCAAT/EnhancerBindingProtein DeltainthePathogenesisofRheumatoidArthritisin Collagen-InducedArthriticMice Ling-HuaChang3,Huei-ShengHuang3,4.,Po-TingWu5.,I-MingJou5.,Min-HsiungPan7 ,Wen- ChangChang6,DennisDingHwaWang8,Ju-MingWang1,2,6* 1InstituteofBioinformaticsandBiosignalTransduction,NationalChengKungUniversity,Tainan,Taiwan,2InfectiousDiseaseandSignalingResearchCenter,National Cheng Kung University, Tainan, Taiwan, 3Institute of Basic Medical Sciences, College of Medicine, Tainan, Taiwan, 4Department of Medical Laboratory Science and Biotechnology,Tainan,Taiwan,5OrthopedicsDepartmentofNationalChengKungUniversityHospital,Tainan,Taiwan,6GraduateInstituteofMedicalSciences,College of Medicine, Taipei Medical University, Taipei, Taiwan, 7Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung, Taiwan, 8Department of BiologicalChemistry,UCIrvineSchoolofMedicine,UniversityofCaliforniaIrvine,Irvine,California,UnitedStatesofAmerica Abstract Background: The up-regulation of CCAAT/enhancer binding protein delta (CEBPD) has frequently been observed in macrophagesinage-associateddisorders,includingrheumatoidarthritis(RA).However,theroleofmacrophageCEBPDin thepathogenesisofRAisunclear. MethodologyandPrincipalFindings:Wefoundthatthecollagen-inducedarthritis(CIA)scoreandthenumberofaffected paws in Cebpd2/2 mice were significantly decreased compared with the wild-type (WT) mice. The histological analysis revealed an attenuated CIA in Cebpd2/2 mice, as shown by reduced pannus formation and greater integrity of joint architecture in affected paws of Cebpd2/2 mice compared with WT mice. In addition, immunohistochemistry analysis revealeddecreasedpannusproliferationandangiogenesisinCebpd2/2micecomparedwithWTmice.CEBPDactivatedin macrophages played a functional role in promoting the tube formation of endothelial cells and the migration and proliferation of synoviocytes. In vivo DNA binding assays and reporter assays showed that CEBPD up-regulated