title: IL-3 inhibits TNF-alpha-induced bone resorption and prevents inflammatory arthritis.
abstract: 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.
authors.affiliation: National Center for Cell Science, University of Pune Campus, Pune, India.
authors.forename: S D
authors.initials: SD
authors.lastname: Yogesha
authors.forename: Shruti M
authors.initials: SM
authors.lastname: Khapli
authors.forename: Rupesh K
authors.initials: RK
authors.lastname: Srivastava
authors.forename: Latha S
authors.initials: LS
authors.lastname: Mangashetti
authors.forename: Satish T
authors.initials: ST
authors.lastname: Pote
authors.forename: Gyan C
authors.initials: GC
authors.lastname: Mishra
authors.forename: Mohan R
authors.initials: MR
authors.lastname: Wani
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D001862:Bone Resorption / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D002358:Cartilage, Articular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000502:physiology*; D007377:Interleukin-3 / Q000008:administration & dosage / Q000502:physiology*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D010007:Osteochondritis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D024043:Collagen Type II; D004268:DNA-Binding Proteins; D018836:Inflammation Mediators; D007377:Interleukin-3; D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha