title: ASC plays a role in the priming phase of the immune response to type II collagen in collagen-induced arthritis.
abstract: Although rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, the role of IL-1β and IL-18 in the pathophysiology of RA has been well established. IL-1β and IL-18 are generated via cleavage of their pro-forms in the presence of the apoptosis-associated speck-like protein containing a caspase recruit domain (ASC), a known adaptor protein that activates procaspase-1. As such, we investigated the involvement of ASC in the progression of murine collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) using ASC-deficient (ASC(-/-)) and wild-type (ASC(+/+)) mice. Analyses were performed by immunohistochemistry for tissues and ELISA for sera. We observed an increase in the expression of ASC, as well as IL-1β and IL-18, in the joints of CIA DBA mice, which indicated that ASC is involved in disease development. Next, we demonstrated that the infiltration of inflammatory cells and cartilage/bone destruction in CIA knee joints were significantly increased in ASC(+/+) mice compared with ASC(-/-) mice. No such differences were noted in ASC(+/+) and ASC(-/-) CAIA mice. In terms of cytokine expression in knee joints, IL-1β and IL-18 were depressed in ASC-deficient CIA mice compared with wild-type mice, but were similarly expressed in CAIA joints in both mice groups. Taken together, we can conclude that ASC is involved in the development of CIA and plays a role in the priming phase of the immune response to type II collagen.
authors.affiliation: Department of Molecular Oncology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, 390-8621, Japan. yamazaki_h@marunouchi.or.jp
authors.forename: Hideshi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Michiko
authors.initials: M
authors.lastname: Takeoka
authors.forename: Masato
authors.initials: M
authors.lastname: Kitazawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Ehara
authors.forename: Naoki
authors.initials: N
authors.lastname: Itano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.forename: Shun'ichiro
authors.initials: S
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D051017:Apoptosis Regulatory Proteins; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D053468:CARD Signaling Adaptor Proteins; D002356:Cartilage / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000276:immunology*; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D007719:Knee Joint / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout
chemical_list: D000906:Antibodies; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D024043:Collagen Type II; D003598:Cytoskeletal Proteins; D018836:Inflammation Mediators; D020382:Interleukin-18; D053583:Interleukin-1beta; C498534:Pycard protein, mouse