Journal article
Evaluation of the Bcl-2 family antagonist ABT-737 in collagen-induced arthritis
KE Lawlor, SD Smith, A van Nieuwenhuijze, DCS Huang, IP Wicks
Journal of Leukocyte Biology | FEDERATION AMER SOC EXP BIOL | Published : 2011
DOI: 10.1189/jlb.0311174
Abstract
Therapeutic manipulation of cellular apoptosis holds great promise for malignant and potentially nonmalignant diseases. A relative resistance to apoptosis in RA synovium is associated with increased expression of prosurvival Bcl-2 family members. In this study, we demonstrate that treatment of DBA/1 mice, prior to the onset of CIA with ABT-737, a BH3 mimetic targeting Bcl-2, Bcl-w, and Bcl-x L, ameliorated disease development. In contrast, treatment of mice with ABT-737 in established CIA did not alter the course of disease. ABT-737 induced lymphopenia, however pathogenic lymphoid populations in CIA mice were less affected, as shown by relatively normal T and B cell responses to CII. Naïve l..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This work was supported by the Reid Charitable Trust (Australia) and the NHMRC (K.E.L., CJ Martin fellow 356267; I.P.W., Clinical Practitioner fellowship 461203; D. C. S. H., fellowship 516701 and program grant 461221). We thank Abbott Laboratories for providing ABT-737; J. Blyth, I. Campbell, and S. Zhang for technical help and advice; K. Mason, E. Carrington, and J. Murphy for discussions; S. Mihajlovic for histology; J. Gilbert and D. Cooper for animal care; F. Battye and staff for cell sorting and J. Corbin for Advia cell counts; K. Rogers for imaging advice; and R. Jones for administrative assistance.