Bim deficiency leads to exacerbation and prolongation of joint inflammation in experimental arthritis

John C. Scatizzi, Emily Bickel, Jack Hutcheson, G. Kenneth Haines, Harris Perlman

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Objective: Rheumatoid arthritis (RA) is characterized by hyperplasia of the synovial lining, inflammation, and destruction of cartilage and bone. Since there are only a few detectable cells undergoing apoptosis in the joint, it is possible that a defect in apoptosis may contribute to synovial hyperplasia. This study sought to identify and characterize the direct role of apoptotic regulators in a mouse model of inflammatory arthritis. Methods. Using a serum transfer model, experimental arthritis was induced in mice lacking the proapoptotic Bcl-2 family genes Bak (Bak-/-), Bax (Bax -/-), or Bim (Bim-/-), as compared with wild-type (WT) control mice. Physical examination for edema of the ankles and histopathologic analysis of ankle sections were used to determine the severity of arthritis. The serum and ankles were examined for production of chemokines and cytokines using enzyme-linked immunosorbent or Luminex-based assays. Results. Bim-/- mice displayed increased severity and prolongation of arthritis. In contrast, Bak-/- and Bax-/- mice showed no difference in the severity of arthritis as compared with WT mice. In addition, Bim-/- mice had elevated levels of proinflammatory chemokines and cytokines, decreased joint and serum production of antiinflammatory cytokines, fewer TUNEL-positive cells, and reduced levels of active caspase 3 as compared with WT mice. Conclusion. These studies are the first to demonstrate a role for the proapoptotic Bcl-2 protein Bim in the effector phase of RA. The findings indicate that Bim potentially functions to repress the effector phase of arthritis by regulating the milieu of the joint and serum, and by inducing apoptosis.

Original languageEnglish (US)
Pages (from-to)3182-3193
Number of pages12
JournalArthritis and Rheumatism
Volume54
Issue number10
DOIs
StatePublished - Oct 2006

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Experimental Arthritis
Joints
Inflammation
Arthritis
Ankle
Apoptosis
Cytokines
Serum
Chemokines
Hyperplasia
Rheumatoid Arthritis
bcl-2 Genes
Immunosorbents
In Situ Nick-End Labeling
Caspase 3
Physical Examination
Cartilage
Edema
Anti-Inflammatory Agents
Bone and Bones

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Bim deficiency leads to exacerbation and prolongation of joint inflammation in experimental arthritis. / Scatizzi, John C.; Bickel, Emily; Hutcheson, Jack; Haines, G. Kenneth; Perlman, Harris.

In: Arthritis and Rheumatism, Vol. 54, No. 10, 10.2006, p. 3182-3193.

Research output: Contribution to journalArticle

Scatizzi, JC, Bickel, E, Hutcheson, J, Haines, GK & Perlman, H 2006, 'Bim deficiency leads to exacerbation and prolongation of joint inflammation in experimental arthritis', Arthritis and Rheumatism, vol. 54, no. 10, pp. 3182-3193. https://doi.org/10.1002/art.22133
Scatizzi, John C. ; Bickel, Emily ; Hutcheson, Jack ; Haines, G. Kenneth ; Perlman, Harris. / Bim deficiency leads to exacerbation and prolongation of joint inflammation in experimental arthritis. In: Arthritis and Rheumatism. 2006 ; Vol. 54, No. 10. pp. 3182-3193.
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