title: Pro-apoptotic Bid is required for the resolution of the effector phase of inflammatory arthritis.
abstract: Rheumatoid arthritis is an autoimmune disease characterized by hyperplasia of the synovial lining and destruction of cartilage and bone. Recent studies have suggested that a lack of apoptosis contributes to the hyperplasia of the synovial lining and to the failure in eliminating autoreactive cells. Mice lacking Fas or Bim, two pro-apoptotic proteins that mediate the extrinsic and intrinsic death cascades, respectively, develop enhanced K/BxN serum transfer-induced arthritis. Since the pro-apoptotic protein Bid functions as an intermediate between the extrinsic and intrinsic apoptotic pathways, we examined the role that it plays in inflammatory arthritis. Mice deficient in Bid (Bid-/-) show a delay in the resolution of K/BxN serum transfer-induced arthritis. Bid-/- mice display increased inflammation, bone destruction, and pannus formation compared to wild-type mice. Furthermore, Bid-/- mice have elevated levels of CXC chemokine and IL-1beta in serum, which are associated with more inflammatory cells throughout the arthritic joint. In addition, there are fewer apoptotic cells in the synovium of Bid-/- compared to Wt mice. These data suggest that extrinsic and intrinsic apoptotic pathways cooperate through Bid to limit development of inflammatory arthritis.
authors.affiliation: Saint Louis University, School of Medicine, Department of Molecular Microbiology and Immunology, Saint Louis, MO 63104, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Scatizzi
authors.forename: Jack
authors.initials: J
authors.lastname: Hutcheson
authors.forename: Emily
authors.initials: E
authors.lastname: Bickel
authors.forename: G Kenneth
authors.initials: GK
authors.lastname: Haines
authors.forename: Harris
authors.initials: H
authors.lastname: Perlman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000172:deficiency*; D019743:Chemokines, CXC / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D016130:Immunophenotyping; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D053583:Interleukin-1beta / Q000097:blood; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; D019743:Chemokines, CXC; D053583:Interleukin-1beta