Disease relevance of CSF1

• The M-CSF, GM-CSF, IL-3, and gamma-IFN were able to alter HIV-1 production under different conditions [1].
• Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis [2].
• 4.0-kb CSF-1 transcripts were detected in 10 of 17 cases of acute myeloblastic leukemia (AML), while c-fms transcripts were detected in 7 of 15 [3].
• Hybridization of the CSF-1 probe to metaphase cells of a fourth patient, with acute nonlymphocytic leukemia de novo, who had a rearrangement of chromosomes 5 and 21 [ins(21;5)(q22;q31.3q33.1)] resulted in labeling of the breakpoint junctions of both rearranged chromosomes; this suggested that CSF-1 is located at 5q33 [4].
• By in situ hybridization, the CSF-1 gene was found to be deleted in the 5q- chromosome of a patient with refractory anemia who had a del(5)(q15q33.3) and in that of a second patient with acute nonlymphocytic leukemia de novo who had a similar distal breakpoint [del(5)(q13q33.3)] [4].

Psychiatry related information on CSF1

• The human CSF1 gene maps to chromosome 1p21-p13, a region previously linked to Alzheimer's disease (AD) [5].
• Because this cellular compartment undergoes major changes during fetal and neonatal life, we examined concurrent CSF-1 expression during human development [6].
• Colony-stimulating factor 1 (CSF-1) is a cytokine involved in hematopoiesis and perhaps more importantly in the early stages of immunological defense mechanisms [7].
• Sera from a total of 31 pregnant women, including 16 of the bed-rest therapy group and 15 of the IDI therapy group, were collected at the 4th, 6th, and 8th gestational weeks and were measured for M-CSF levels, using the enzyme-linked immunoadsorbent assay (ELISA) method established by Hanamura et al [8].

High impact information on CSF1

• We now report that E5 can cooperate with human EGF receptors and with human CSF-1 receptors to induce cellular transformation of NIH 3T3 cells [9].
• Similarities in chromosomal localization, organization, and encoded amino acid sequences suggest that the genes encoding the CSF-1 and PDGF receptors arose through duplication [10].
• Like the v-fms oncogene product, receptors bearing the activating mutation retained high-affinity binding sites for CSF-1 but were retarded in transport to the cell surface and were phosphorylated on tyrosine in the absence of ligand [11].
• Although the activating mutation does not affect the CSF-1 binding site in the receptor extracellular domain, it must induce a conformational change that mimics the effect of ligand binding, resulting in CSF-1-independent signals for cell growth [11].
• We show that the human c-fms gene stimulates growth of mouse NIH 3T3 cells in agar in response to human recombinant CSF-1, indicating that receptor transduction is sufficient to induce a CSF-1 responsive phenotype [12].

Chemical compound and disease context of CSF1

• Furthermore, the increase in PC turnover induced by CSF-1 was sensitive to pertussis toxin [13].
• Co-expression of M-CSF transcripts and protein, FMS (M-CSF receptor) transcripts and protein, and steroid receptor content in adenocarcinomas of the ovary [14].
• These data indicate that M-CSF does not act as a regulator of bone turnover, but GM-CSF may cause bone resorption by stimulating the synthesis of PGE2 in bone [15].
• Furthermore, the product of the proto-oncogene fms (c-fms) may be related or identical to the receptor for macrophage colony-stimulating factor (CSF-1). v-fms is the transforming gene of the McDonough strain of feline sarcoma virus (SM-FeSV) and belongs to the family of src-related oncogenes which have tyrosine-specific kinase activity [16].
• Pretreatment of THP-1 cells with pertussis toxin inhibited the increase in PKC activity but not the induction of TNF transcripts by M-CSF [17].

Biological context of CSF1

• We confirm that translocations involving 1p13 are present in a majority of cases of TGCT and PVNS and show that CSF1 is the gene at the chromosome 1p13 breakpoint [18].
• Formation of sequences by both BRG1 and the Z-DNA is required for effective chromatin remodeling of the CSF1 promoter [19].
• Dosage analysis at the CSF1 and CSF1R loci in a new case of partial trisomy 5q [20].
• The biologically active form of M-CSF is a disulfide-linked dimer that activates an intrinsic tyrosine kinase activity on the M-CSF receptor by inducing dimerization of the receptor molecules [21].
• Because CSF-1 regulates the survival, proliferation and chemotaxis of macrophages and supports their activation, this factor is involved in the pathogenesis of several diseases [22].

Anatomical context of CSF1

• A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells [18].
• The ARH9 gene locus was previously assigned to the telomeric region of chromosome 5q by isotopic chromosomal in situ hybridization and Southern analysis of somatic cell hybrid DNAs; the gene was noted to cosegregate with the CSF1 gene locus in human-rodent somatic cell hybrids carrying partial chromosomes 5, together with other human chromosomes [23].
• CSF-1-regulated tissue macrophages are important for innate immunity and for tissue development and function [22].
• Most tissue macrophages and osteoclasts are regulated by colony-stimulating factor-1 (CSF-1, also known as macrophage CSF) [22].
• Biological activity of IL-3 and CSF-1 was demonstrable in supernatant fluids of NK cells stimulated with PDBu/A23187 and CD16 ligands/rIL-2, respectively [24].

Associations of CSF1 with chemical compounds

• Tumor necrosis factor was present in 75% of CSF1 samples; the mean concentration was 787 +/- 3358 pg/ml [25].
• CSF-1 was synthesized as an integral transmembrane glycoprotein that was rapidly dimerized through disulfide bonds [26].
• The comparative stability of M-CSF mRNA from cord versus adult MNCs was next determined by actinomycin D decay studies [27].
• These findings show that GM-CSF, M-CSF, and IL-3 selectively enhance O2- release in human monocytes triggered by receptor-mediated agonists after short-term preincubation [28].
• There was a significant increase in the induction of M-CSF mRNA by CHX treatment in both cord and adult MNCs [27].
• Activation of WASP in response to treatment with CSF-1 was also shown to be phosphatidylinositol 3-kinase-dependent [29].

Physical interactions of CSF1

• The reduction in CSF-1-binding activity was reversed by prolonged incubation at 37 degrees C even in the presence of TNF [30].
• Furthermore, gel-shift analysis of APL cells showed elevated levels of PU.1 binding activity to the M-CSF receptor promoter, particularly after ATRA stimulation [31].
• CONCLUSIONS: MM and M-CSF-induced VSMC killing requires MM binding to VSMC mediated by Mac-1 and ICAM-1, and Fas-FasL interaction [32].

Enzymatic interactions of CSF1

• Although c-fms and several other proteins were shown to be phosphorylated in response to M-CSF, the functional consequences of this phosphorylation remain unclear [33].
• Recently c-Cbl has been reported to be phosphorylated upon CSF-1 stimulation [34].
• The induction of M-CSF mRNA expression by either oxidized low density lipoprotein (ox-LDL) or tumor necrosis factor-alpha (TNF alpha) was attenuated by NO donors, S-nitrosoglutathione (GSNO), sodium nitroprusside (SNP), and 3-morpholinosydnonimine, but not by cGMP analogues, glutathione, or nitrite [35].

Co-localisations of CSF1

• CD68+ monocytes and M-CSF+ fibroblast-like synoviocytes were colocalized in regions adjacent to the destroyed bone of RA patients [36].

Regulatory relationships of CSF1

• The present studies demonstrate that the granulocyte-macrophage colony-stimulating factor (GM-CSF) also induces CSF-1 transcripts in monocytes [37].
• NIH 3T3 cells cotransfected with the human c-fms proto-oncogene together with a 1.6-kilobase cDNA clone encoding a 256-amino-acid precursor of the human mononuclear phagocyte colony-stimulating factor CSF-1 (M-CSF) undergo transformation by an autocrine mechanism [26].
• The ligand for flt-3 (FLT3L) exhibits striking structural homology with stem cell factor (SCF) and monocyte colony-stimulating factor (M-CSF) and also acts in synergy with a range of other hematopoietic growth factors (HGF) [38].
• Network formation by these HUVECs after treatment with supernatants from monocytes stimulated with M-CSF were inhibited by anti-VEGF, but not by the isogenic control, Abs [39].
• We have previously shown that a low concentration of CSF-1 (1 U/ml) can trigger human immature monocytic progenitor proliferation in the presence of low concentrations of IL3 (1.7 U/ml) [40].

Other interactions of CSF1

• Accumulation of CSF-1 mRNA is observed only in NK cells stimulated with both CD16 ligands and rIL-2, whereas accumulation of IL-3 mRNA is observed only in NK cells stimulated with PDBu/A23187 [24].
• The effects of CSF-1 are mediated through binding to specific, high-affinity surface receptors encoded by the c-fms gene [3].
• Terminal granulocytic or monocytic differentiation was observed when AML-193 cells were treated with RA and G-CSF, or D3 and M-CSF, respectively, as evaluated by cell morphology, analysis of surface antigens, and phagocytic functions [41].
• When the addition of IL-6 to M-CSF-supplemented cultures was delayed for more than one day after the beginning of culture, enhancement of macrophage colony formation was lost [42].
• (5) When cultured in the presence of M-CSF and IL-4, UG3 cells differentiate into osteoclast-like multinucleated giant cells capable of bone resorption and display tartrate-resistant acid phosphatase (TRAP) activity [43].

Analytical, diagnostic and therapeutic context of CSF1

• The structure of a recombinant human M-CSF dimer, determined at 2.5 angstroms by x-ray crystallography, contains two bundles of four alpha helices laid end-to-end, with an interchain disulfide bond [21].
• CSF-1 and c-fms gene expression was investigated in fresh human acute myeloblastic leukemic cells by Northern blot hybridization using cDNA probes [3].
• In response to both adhesion and recombinant human GM-CSF (rhGM-CSF) stimulation for 120 hours, radioimmunoassays and bioassays showed that cord MNCs produced twofold to threefold less M-CSF protein compared with adult MNCs [27].
• Although M-CSF has been used for myelosuppression due to chemotherapy in patients with solid tumors, the effect of exogenous M-CSF on tumor angiogenesis has not been studied [44].
• RT-PCR analysis of cytokine and growth factor mRNA in MSCs and MDSCs revealed a very similar pattern of mRNAs including IL-6, -7, -8, -11, -12, -14, and -15, M-CSF, Flt-3 ligand, and SCF [45].

References