The human surfactant protein (SP)-C gene promoter was used to direct expression of mouse granulocyte macrophage colony-stimulating factor (GM-CSF; SP-C-GM mice) in lung epithelial cells in GM-CSF-replete (GM+/+) or GM-CSF null mutant (GM-/-) mice. Lung weight and volume were significantly increased in SP-C-GM mice compared with GM+/+ or GM-/- control mice. Immunohistochemical staining demonstra...

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unclear etiology. This study was conducted to identify critical factors involved in the synovial hyperplasia in RA pathology. We applied cDNA microarray analysis to profile the gene expressions of RA fibroblast-like synoviocytes (FLSs) from patients with RA. We found that the MLN51 (metastatic lymph node 51) gene, identified in ...

The colony-stimulating factor-1 (CSF-1) regulates survival, growth, and differentiation of monocytes by binding to a single class of high-affinity receptors. The CSF-1 receptor is identical to the product of the c-fms protooncogene. The present studies monitored the effects of TPA and CSF-1 on c-fms gene expression in human monocytes. The results demonstrate that TPA downmodulates the constitut...

Colony-stimulating factor-1 (CSF-1) induces expression of immediate early gene, such as c-myc and c-fos and delayed early genes such as D-type cyclins (D1 and D2), whose products play essential roles in the G1 to S phase transition of the cell cycle. Little is known, however, about the cytoplasmic signal transduction pathways that connect the surface CSF-1 receptor to these genes in the nucleus...

The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). It plays important roles in development and in innate immunity by regulating the development of most tissue macrophages and osteoclasts, of Langerhans cells of the skin, of Paneth cells of the small intestine, and of brain microglia. It also regulates the di...

GM-CSF signals through JAK2 and STAT5 and stimulates the expression of STAT5 target genes, such as pim-1 and CIS. Analyzed by EMSA, GM-CSF stimulation led to much stronger STAT5 DNA-binding to pim-1 or CIS GAS elements in primary human monocytes compared with mature macrophages. Similarly, GM-CSF-induced expression of pim-1 and CIS mRNAs was much stronger in monocytes. These differencies were n...

Colony-stimulating factor-1 (CSF-1) activation of the CSF-1 receptor (CSF-1R) causes Cbl protooncoprotein tyrosine phosphorylation, Cbl-CSF-1R association and their simultaneous multiubiquitination at the plasma membrane. The CSF-1R is then rapidly internalized and degraded, whereas Cbl is deubiquitinated in the cytoplasm without being degraded. We have used primary macrophages from gene-target...

Recently, the gene for a novel mammalian hematopoietic growth factor homologous to murine interleukin 3 was isolated from a gibbon T cell line and expressed in monkey COS cells. The factor, termed multi-colony stimulating factor (multi-CSF) or interleukin 3, is stimulatory to human target cells. We investigated the range of enriched human bone marrow and fetal liver hematopoietic progenitors re...

Marrow stromal cells are thought to regulate hematopoiesis by producing colony-stimulating factors (CSFs) and other cytokines, either constitutively or in response to mediators such as interleukin-1 alpha (IL-1 alpha) or tumor necrosis factor-alpha (TNF alpha). The mechanisms by which these inflammatory cytokines induce CSF expression in stromal cells are not fully defined. In this study, we us...

The effects of colony-stimulating factor 1 (CSF-1), the primary regulator of mononuclear phagocyte production, are thought to be mediated by the CSF-1 receptor (CSF-1R), encoded by the c-fms proto-oncogene. To investigate the in vivo specificity of CSF-1 for the CSF-1R, the mouse Csf1r gene was inactivated. The phenotype of Csf1(-)/Csf1r(-) mice closely resembled the phenotype of CSF-1-nullizyg...