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The antibody atliximab attenuates collagen-induced arthritis by neutralizing AIMP1, an inflammatory cytokine that enhances osteoclastogenesis

 Shin Hee Hong  ;  Jin Gu Cho  ;  Kang Jun Yoon  ;  Dae-Seog Lim  ;  Chul Hoon Kim  ;  Sang-Won Lee  ;  Sang Gyu Park 
 BIOMATERIALS, Vol.44 : 45-54, 2015 
Journal Title
Issue Date
Animals ; Antibodies/pharmacology* ; Antibodies, Neutralizing/pharmacology* ; Arthritis, Experimental/diagnostic imaging ; Arthritis, Experimental/pathology* ; Cell Line ; Cytokines/metabolism* ; Disease Models, Animal ; Humans ; Inflammation Mediators/metabolism* ; Mice ; Neoplasm Proteins/metabolism* ; Osteoclasts/drug effects ; Osteoclasts/pathology* ; Osteogenesis/drug effects* ; RANK Ligand/pharmacology ; RNA-Binding Proteins/metabolism* ; Recombinant Fusion Proteins/pharmacology* ; X-Ray Microtomography
AIMP1 ; Arthritis ; Cytokine ; Osteoclastogenesis
ARS-interacting multifunctional protein 1 (AIMP1) induces production of inflammatory cytokines from immune cells. Since osteoclastogenesis is promoted by positive regulation of inflammatory cytokines, whether AIMP1 could promote osteoclastogenesis was investigated. AIMP1 induced osteoclastogenesis and acted synergistically with RANKL to promote osteoclastogenesis. Down-regulation of CD23, an AIMP1 receptor, abolished AIMP1-mediated osteoclastogenesis. Enzyme-linked immunosorbent assays showed that the AIMP1 level was significantly higher in the peripheral blood (PB) and synovial fluid of rheumatoid arthritis patients than in normal PB. A monoclonal antibody (clone 15B3AF) that blocked the cytokine activity of AIMP1 inhibited the AIMP1-mediated production of inflammatory cytokines. Clone 15B3AF inhibited the AIMP1-mediated osteoclastogenesis in vitro. We then cloned the complementary determining regions of clone 15B3AF and generated a chimeric antibody (atliximab). In a collagen-induced arthritis mouse model (CIA), atliximab administration significantly attenuated disease severity and improved various histopathological parameters. Three-dimensional micro-computed tomography scanning confirmed that atliximab enhanced the joint structures in CIA mice. Furthermore, atliximab decreased the expression of inflammatory cytokines in the serum and inflamed joints of CIA mice. Taken together, our findings suggest that AIMP1 exacerbates RA by promoting inflammation and osteoclastogenesis and that atliximab could be developed as a therapeutic antibody to target inflammatory diseases, including RA.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Lee, Sang-Won(이상원) ORCID logo https://orcid.org/0000-0002-8038-3341
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