| First Author | Yogesha SD | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 1 | Pages | 361-70 |
| PubMed ID | 19109167 | Mgi Jnum | J:142893 |
| Mgi Id | MGI:3822390 | Doi | 10.4049/jimmunol.182.1.361 |
| Citation | Yogesha SD, et al. (2009) IL-3 inhibits TNF-alpha-induced bone resorption and prevents inflammatory arthritis. J Immunol 182(1):361-70 |
| abstractText | 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-1alpha, TGF-beta(1), TGF-beta(3), IL-6, and PGE(2). 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. |
