Disease relevance of Csf2

• We also provide evidence to indicate that Nf1 gene loss induces myeloproliferative disease through a Ras-mediated hypersensitivity to granulocyte/macrophage-colony stimulating factor (GM-CSF) [1].
• The effects of CSF in mice pretreated with LF were not mimicked by 0.1-100 ng E. coli lipopolysaccharide [2].
• These data establish that patients with acquired PAP have an associated impaired responsiveness to GM-CSF that is potentially pathogenic in the development of their lung disease [3].
• We show GM-CSF to be the single most effective cytokine for enhancing both cellular and humoral immunity to two previously characterized HIV-1 MN vaccine constructs [4].
• IFN-gamma, TNF-alpha, IL-1, and granulocyte-macrophage CSF (GM-CSF) play an important role in host resistance to infection with nontyphoid Salmonella [5].

Psychiatry related information on Csf2

• Lymphocytes from spleens and draining lymph nodes of mice primed with Id-KLH plus GM-CSF, but not with Id-KLH alone, demonstrated significant proliferation to Id in vitro without any biased production of interferon gamma or interleukin 4 protein or mRNA [6].
• These results demonstrate the feasibility of integrating GM-CSF vaccines in the postautologous BMT setting and suggest mechanisms that may contribute to the observed efficacy of immunization during the critical period of immune reconstitution [7].
• We recently reported [Proc. Natl. Acad. Sci. USA 95 (1998) 3239] that in patients with severe depression there is a decrease in the CSF levels of 3alpha,5alpha-TH PROG, which is normalized by treatment with drugs (i.e. fluoxetine) that improve psychopathology [8].
• The CSF levels of both metabolites were increased in sporadic CJD (n = 52) and familial CJD (n = 10) patients when compared with a group of patients with noninflammatory disorders [9].
• Plaque-associated disruption of CSF and plasma amyloid-beta (Abeta) equilibrium in a mouse model of Alzheimer's disease [10].

High impact information on Csf2

• Both CSF-1 and GM-CSF are responsible for transition of cells of the M phi lineage from bone marrow to blood, and from blood to tissues, and have a critical extramedullary role [11].
• These data define a specific role for neurofibromin in negatively regulating GM-CSF signaling through Ras in haematopoietic cells and they suggest that hypersensitivity to GM-CSF may be a primary event in the development of JCML [12].
• Single FDC-Pmix cells infected with retroviral vectors expressing GM-CSF are induced to differentiate into granulocytes and macrophages [13].
• Expression of the GM-CSF gene after retroviral transfer in hematopoietic stem cell lines induces synchronous granulocyte-macrophage differentiation [13].
• Factor switching experiments have shown that both multi-CSF and GM-CSF act dominantly and in a factor concentration dependent manner to suppress c-fms expression [14].

Chemical compound and disease context of Csf2

• The mice receiving the AAV/IL-10 virus had significantly lower levels of atherogenesis (Sudan IV-staining and histology) than the untreated or the AAV/GM-CSF-treated animals, dropping from 53% to 17% (p < 0.05) [15].
• These results indicate that the combination use of IL-3 and GM-CSF in vivo is only a partially effective growth factor/cytokine treatment to ameliorate the hematopoietic toxicity associated with the use of the anti-viral drug zidovudine [16].
• In this study, we show that, in contrast to the response to the commonly used i.p. irritant, thioglycolate medium, an Ag-specific methylated BSA-induced peritonitis in GM-CSF(-/-) mice was severely compromised [17].
• Finally, to test the in vivo relevance of our findings, we showed that GM-CSF restored the survival of dexamethasone- or cyclosporine A-immunosuppressed mice from an otherwise lethal infection with Salmonella typhimurium [18].
• To understand the mechanism involved in the exacerbation of psoriasis by lithium salts, the IL-1, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in murine skin injected with TNF in combination with LiCl were studied [19].

Biological context of Csf2

• In total, 118 distinct, putative exons were sequenced and characterized, mapping up to 29 distinct genes to the mouse cluster, including Il4 and Csf2 [20].
• Furthermore, these results argue strongly that IL-3 and GM-CSF are not critical to early hematopoiesis [21].
• Bone marrow cells from these animals displayed a strong increase in apoptotic cell death during GM-CSF-dependent functional maturation in vitro [22].
• IL-3 and GM-CSF were not expressed during the first 24 days of ES cell differentiation [21].
• Regulation of MHC class II gene expression in macrophages by hematopoietic colony-stimulating factors (CSF). Induction by granulocyte/macrophage CSF and inhibition by CSF-1 [23].

Anatomical context of Csf2

• Endotoxin-induced expression of other genes such as Il12b and Csf2 is also abrogated in IkappaBzeta-deficient macrophages [24].
• Stimulation of multipotential, erythroid and other murine haematopoietic progenitor cells by adherent cell lines in the absence of detectable multi-CSF (IL-3) [25].
• Thus IL-3, IL-5, and GM-CSF influence eosinophil function and survival, and may be generated by T lymphocytes and/or alveolar macrophages within the airways in asthma [26].
• Alveolar macrophages derived from asthmatic subjects produce twofold to threefold more GM-CSF than do those from normal control subjects [26].
• Taken together, these data suggest that neurofibromin is required to downregulate Ras activation in myeloid cells exposed to GM-CSF [27].

Associations of Csf2 with chemical compounds

• In contrast to mitogen-activated Rel-/- T cells, lipopolysaccharide-stimulated Rel-/- macrophages produce higher than normal levels of GM-CSF [28].
• In contrast, injection of a polyethylene glycol-modified form of granulocyte/macrophage colony-stimulating factor (GM-CSF) into mice only expands the myeloid-related DC subset [29].
• The cell permeable antioxidant pyrrolidine dithiocarbamate (PDTC) decreased the intracellular levels of ROS and inhibited tyrosine phosphorylation induced by GM-CSF in MO7e cells, suggesting that ROS generation plays an important role in GM-CSF signaling [30].
• In summary, mature hematopoietic cells with a null mutation of the betac receptor were unable to perform GM-CSF-mediated hematopoietic cell functions including glucose transport, but responded normally to a range of other ligands [31].
• The induction of IL-5 mRNA by phorbol 12-myristate 13-acetate (PMA) stimulation was found to be cyclosporin A-resistant, in contrast to the induction of IL-2 and GM-CSF mRNAs [32].

Physical interactions of Csf2

• By comparison, in peritoneal macrophages, GM-CSF induced a complex with the properties of a truncated form of STAT5 [33].
• The biologic actions of GM-CSF are mediated by its binding to the alpha and beta subunits of the GM-CSF receptor (GM-CSFRalpha and betac, respectively) [34].
• The Tg CD8(+) T cells can bind the granulocyte-macrophage colony-stimulating GM-CSF produced by antigen stimulation, but the GM-CSF binding results in delivery of an IL-2R signal [35].
• Granulocyte macrophage colony stimulating factor (GM-CSF) activity is regulated by a GM-CSF binding molecule in Wallerian degeneration following injury to peripheral nerve axons [36].
• These results in GM-CSF-treated macrophages reveal a relationship between histone deacetylase complexes and STAT5 in the regulation of gene expression [37].

Enzymatic interactions of Csf2

• Our data indicate that macrophage hypersensitivity to GM-CSF may be a major factor in motheaten pathogenesis and that HCP may dephosphorylate novel substrates critical in GM-CSF mitogenic signaling [38].

Regulatory relationships of Csf2

• Human JMML and murine Nf1-deficient cells are hypersensitive to granulocyte-macrophage colony-stimulating factor (GM-CSF) in methylcellulose cultures [39].
• The work provides evidence that IL-18 is expressed by osteoblasts and inhibits OCL formation via GM-CSF production and not via IFN-gamma production [40].
• These results have led us to propose a model for HGF synergy whereby one mechanism of action the investigated synergistic cytokines might be the ability to induce increased expression of CSF receptors [41].
• In the present study, we show that IL-4 inhibits the production of GM-CSF in the IL-1 alpha-stimulated murine B-cell line M12.4 [42].
• To determine the mechanism(s) by which interleukin-1 (IL-1) promotes granulopoiesis in vivo, we examined the effect of in vivo administration of IL-1 alpha on colony-stimulating factor (CSF) receptor expression on bone marrow cells (BMCs) and whether this directly correlated with progenitor cell responsiveness [43].

Other interactions of Csf2

• The initial proliferation of these cells can also be stimulated by two other glycoproteins, granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF), although continued proliferation and differentiation requires the subsequent presence of multi-CSF [25].
• The transcription of other cytokines including IL-13, GM-CSF, and TNF alpha was also affected, though to a lesser degree [44].
• Neither IL-2, IL-4, GM-CSF, nor endotoxin had any significant mast cell chemotactic activity [45].
• However examination of the subchromosomal region containing all three loci by pulsed field gel analysis showed that SPARC is at least 400-500 kb distant from the region containing the two CSF genes [46].
• Expression of the GM-CSF gene in EL-4 cells was detected independent of CsA, whereas CsA inhibited the expression of the IL-2 gene [47].

Analytical, diagnostic and therapeutic context of Csf2

• The GM-CSF molecule was detected by ELISA in medium conditioned by in vitro and in vivo degenerating peripheral nerves as of the 4th h after injury [48].
• GM-CSF activity was demonstrated by two independent bioassays, and repressed by activity blocking antibodies [48].
• GM-CSF mRNA was detected by PCR in in vitro and in vivo degenerating nerves, but not in intact nerves [48].
• Analysis of physical distances by pulsed field gel electrophoresis demonstrated further that the two CSF genes lie within 230 kb of each other [46].
• These preclinical data emphasize that GM-CSF gene immunotherapy deserves clinical evaluation in AML [49].

References