Pro-apoptotic Bid is required for the resolution of the effector phase of inflammatory arthritis.
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.
Scatizzi
John C
JC
Saint Louis University, School of Medicine, Department of Molecular Microbiology and Immunology, Saint Louis, MO 63104, USA.
Hutcheson
Jack
J
Bickel
Emily
E
Haines
G Kenneth
GK
Perlman
Harris
H
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
D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; D019743:Chemokines, CXC; D053583:Interleukin-1beta