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The Journal of Immunology, 2009, 182, 361-370
Copyright © 2009 by The American Association of Immunologists, Inc.
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IL-3 Inhibits TNF-{alpha}-Induced Bone Resorption and Prevents Inflammatory Arthritis1

S. D. Yogesha, Shruti M. Khapli, Rupesh K. Srivastava, Latha S. Mangashetti, Satish T. Pote, Gyan C. Mishra and Mohan R. Wani2

National Center for Cell Science, University of Pune Campus, Pune, India

IL-3, a cytokine secreted by activated T cells is well known to regulate the proliferation, differentiation, and survival of pluripotent hematopoietic stem cells. IL-3 functions as a link between the immune and the hematopoietic system. In this study, we suggest an important new role of IL-3 in inhibition of TNF-{alpha}-induced bone resorption in vitro and prevention of inflammatory arthritis in mice. We show here that IL-3 potently and irreversibly inhibits TNF-{alpha}-induced bone resorption in hematopoietic precursors of monocyte/macrophage lineage. IL-3 showed an inhibitory effect on TNF-{alpha}-induced bone resorption even in the presence of proinflammatory cytokines such as IL-1{alpha}, TGF-β1, TGF-β3, IL-6, and PGE2. We found that IL-3 prevented TNF-{alpha}-induced c-fos nuclear translocation and AP-1 DNA-binding activity. Interestingly, IL-3 pretreatment prevented the development of inflammatory arthritis in mice induced by a mixture of anti-type II collagen mAbs and LPS. Furthermore, IL-3 prevented cartilage and bone loss in the joints indirectly through inhibition of inflammation. Thus, we provide the first evidence that IL-3, a strong regulator of hematopoiesis, also plays an important role in inhibition of TNF-{alpha}-induced bone resorption and prevention of inflammatory arthritis in mice.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by the Department of Biotechnology, Government of India. S.D.Y. and S.M.K. received Senior Research Fellowships from the Council for Scientific and Industrial Research (New Delhi, India).

2 Address correspondence and reprint requests to Dr. Mohan R. Wani, National Center for Cell Science, University of Pune Campus, Ganeshkhind Road, Pune-411007, India. E-mail address: mohanwani{at}nccs.res.in

3 Abbreviations used in this paper: RA, rheumatoid arthritis; RANKL, receptor activator of NF-{kappa}B ligand; OPG, osteoprotegerin; TRAP, tartrate-resistant acid phosphatase; CTX-I, C-terminal telopeptide of type I collagen; BMD, bone mineral density.






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