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: S D Yogesha, Shruti M Khapli, Rupesh K Srivastava, Latha S Mangashetti, Satish T Pote, Gyan C Mishra, Mohan R Wani
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 182 Issue 1 Pg. 361-70 (Jan 01 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19109167 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Collagen Type II
• DNA-Binding Proteins
• Inflammation Mediators
• Interleukin-3
• Lipopolysaccharides
• Proto-Oncogene Proteins c-fos
• Transcription Factor AP-1
• Tumor Necrosis Factor-alpha

Topics

• Active Transport, Cell Nucleus (immunology)
• Animals
• Antibodies, Monoclonal (administration & dosage)
• Arthritis, Experimental (immunology, metabolism, prevention & control)
• Bone Resorption (immunology, pathology, prevention & control)
• Cartilage, Articular (immunology, metabolism, pathology)
• Cell Nucleus (immunology, metabolism)
• Cells, Cultured
• Collagen Type II (immunology)
• DNA-Binding Proteins (antagonists & inhibitors, metabolism)
• Inflammation Mediators (administration & dosage, physiology)
• Interleukin-3 (administration & dosage, physiology)
• Lipopolysaccharides (administration & dosage)
• Mice
• Mice, Inbred BALB C
• Organ Culture Techniques
• Osteochondritis (immunology, metabolism, prevention & control)
• Protein Binding (genetics, immunology)
• Proto-Oncogene Proteins c-fos (antagonists & inhibitors, metabolism)
• Transcription Factor AP-1 (antagonists & inhibitors, metabolism)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, physiology)