Disease relevance of Il3

• Murine hematopoietic cells can be transformed in vitro by recombinant retroviruses that express the myb oncogene, and hematopoietic growth factor (HGF)-dependent myeloid cell lines can be derived from these transformed primary cells [1].
• The induction of apoptosis by TGF-beta 1 in a different myeloid leukemia (7-M12) was inhibited by GM-CSF and IL-3 but not by the other cytokines [2].
• Expression of the interleukin-3 and granulocyte-macrophage colony-stimulating factor genes in Friend spleen focus-forming virus-induced erythroleukemia [3].
• Primitive chronic myeloid leukemia cells display a unique autocrine interleukin 3 (IL-3)/granulocyte-colony-stimluating factor (G-CSF) mechanism that may explain their abnormal proliferation and differentiation control [4].
• The immune response of the beta c/IL-3 double-mutant mice to Listeria mono-cytogenes was normal, as was hematopoietic recovery after administration of the cytotoxic drug, 5-fluorouracil [5].

Psychiatry related information on Il3

• Through the production of these cytokines with IL 3-like capacity keratinocytes may participate in the regulation of the activity of different hematopoietic cells and thereby turn on early nonspecific host defense mechanisms against transformed cells and various harmful microbial organisms [6].
• Upon injection of v-H-ras-expressing, transformation-competent cells into mice, the final, fully malignant phenotype developed with a long latency period and was marked in vitro by independence of exogenous IL-3 and by autocrine IL-3 stimulation [7].

High impact information on Il3

• The panspecific hemopoietin of activated T lymphocytes (interleukin-3) [8].
• The lipocalin mouse 24p3 has been implicated in diverse physiological processes, including apoptosis due to interleukin-3 (IL-3) deprivation and iron transport [9].
• Transfection of the human bcl-2 gene into an interleukin-3 (IL-3)-dependent, multipotent hemopoietic cell line allowed these cells to survive in the absence of IL-3, both in serum-containing and serum-deprived conditions, and this survival was accompanied by multilineage differentiation [10].
• Stimulation via cytokine receptors such as IL-2 and IL-3 receptors, but not by the EGF receptor (EGFR), induces cells of the BAF-B03 hematopoietic cell line to transit the cell cycle [11].
• Our data indicate that activation of the GM-CSF receptor induces differentiation of stem cells by an instructive mechanism that can be blocked by the activated IL-3 receptor [12].

Chemical compound and disease context of Il3

• The synergistic activity of IL-3 was observed over a wide range of Escherichia coli or Salmonella enteritidis LPS concentrations [13].
• Use of EPO or IL-3, either alone or in combination, failed to reverse zidovudine-induced neutropenia [14].
• Upon expression in 32Dcl3 growth factor-dependent myeloid precursor cells, STAT5 activation-deficient BCR/ABL SH3+SH2 domain mutants functioned as tyrosine kinase and activated Ras, but failed to protect from apoptosis induced by withdrawal of interleukin 3 and/or serum and did not induce leukemia in severe combined immunodeficiency mice [15].
• An interleukin-3 (IL-3)-dependent mouse myeloid cell line, FDC-P1, was infected with a murine retrovirus vector containing v-fms linked to a gene encoding resistance to neomycin (neo) [16].
• NFS/N1.H7 cells were inhibited in interleukin-3-dependent proliferation (dose range, IL-3 10 to 100 U/mL) by PGE1 79 +/- 11%, by pertussis toxin 51 +/- 9%, and by the combination 92 +/- 2%, whereas H7 Neo RAS.F3 was inhibited 51 +/- 7%, 6 +/- 2%, or 58 +/- 9% by PGE1, pertussis toxin, and the combination, respectively [17].

Biological context of Il3

• Interleukin-3 (IL-3) binds to its receptor with high and low affinities, induces tyrosine phosphorylation, and promotes the proliferation and differentiation of hematopoietic cells [18].
• Furthermore, these results argue strongly that IL-3 and GM-CSF are not critical to early hematopoiesis [19].
• IL-3 and GM-CSF were not expressed during the first 24 days of ES cell differentiation [19].
• It is interesting to note that omission of either SF or Ep from this assay markedly enhanced the rate of differentiation and reduced total cell numbers, whereas omission of IL-3 had no effect on the rate of differentiation and only slightly reduced cell numbers [20].
• Comparative effects in vivo of recombinant murine interleukin 3, natural murine colony-stimulating factor-1, and recombinant murine granulocyte-macrophage colony-stimulating factor on myelopoiesis in mice [21].

Anatomical context of Il3

• BSF-1 activity, including the ability to enhance the growth of IL-3-dependent mast cells, was detected in the supernatants of transformed mast cells [22].
• Fibroblasts transfected with the complementary DNA bound IL-3 with a low affinity [dissociation constant (Kd) of 17.9 +/- 3.6 nM] [18].
• These cells represent the first nontransformed cell lines which can be maintained in growth factors other than IL-3 and which differentiate in the presence of physiologic signals [23].
• The two murine haemopoietic growth factors, granulocyte-macrophage colony stimulating factor (GM-CSF) and Multi-CSF (interleukin 3) stimulate the proliferation and differentiation of an overlapping set of haemopoietic progenitor cells and are produced coordinately following activation of T lymphocytes [24].
• Both high affinity IL-3Rs expressed on a mouse T cell line, CTLL-2, showed similar IL-3 binding properties and transmitted a growth signal in response to IL-3 [25].

Associations of Il3 with chemical compounds

• It is well established that murine multipotential and committed erythroid progenitor cells require the presence of a glycoprotein, termed multi-CSF (multi-colony-stimulating factor, IL-3) for clonal proliferation and differentiation in vitro [26].
• Mouse bone marrow-derived mast cells (BMMCs) developed with interleukin 3 (IL-3) can be stimulated by c-kit ligand (KL) and accessory cytokines over a period of hours for direct delayed prostaglandin (PG) generation or over a period of days to prime for augmented IgE-dependent PG and leukotriene (LT) production, as previously reported [27].
• IL-4 inhibited the priming for increased IgE-dependent PGD2 and LTC4 production to the level obtained by activation of BMMCs maintained in IL-3 alone with an IC50 of approximately 0.2 ng/ml [27].
• First, we tested the effects of IL-3 on lymphohematopoietic progenitors by using lineage-negative (Lin-) marrow cells of 5-fluorouracil (5-FU)-treated mice in the two-step methylcellulose culture we reported previously [28].
• Maximal levels of pro-B cell expansion, generally resulting in 15- to 30-fold increases in cellularity, were obtained in cultures supplemented with optimal doses of FL + IL-7 + IL-3 [29].

Physical interactions of Il3

• Binding of IL-3 to the IL-3 receptor (IL-3R) and binding of EPO to the EPOR both induce changes in intracellular tyrosine and serine/threonine phosphorylation; the phosphorylation of a number of polypeptides appears to be a shared response upon cytokine stimulation [30].
• Stem cell factor activates STAT-5 DNA binding in IL-3-derived bone marrow mast cells [31].
• IL-3 transmits its signal through a specific cell surface receptor which consists of a primary binding alpha subunit (IL-3R alpha) and a signaling beta subunit that is shared by the IL-5 and GM-CSF receptors [32].
• Non-B, non-T cells from spleen and bone marrow of naive mice produce IL-4 upon stimulation by plate-bound IgE or IgG2a in the presence of IL-3 [33].
• P210 Bcr-Abl interacts with the interleukin 3 receptor beta(c) subunit and constitutively induces its tyrosine phosphorylation [34].

Enzymatic interactions of Il3

• Cross-linking of CD16/Jak2 stimulates the tyrosine phosphorylation of a large group of proteins that are also phosphorylated after the addition of IL-3 or GM-CSF and include proteins of 145, 97, 67, 52, and 42 kDa [35].
• Active, but not inactive, forms of Akt were found to phosphorylate BAD in vivo and in vitro at the same residues that are phosphorylated in response to IL-3 [36].
• We could reveal that the C-terminal half of the Tec N-terminal unique domain (NTec2 region) can bind to a set of tyrosine-phosphorylated cellular proteins in vitro in an IL-3-dependent manner [37].
• Among the NTec2-bound Lyn proteins, only the p56 form seems to be inducibly tyrosine-phosphorylated in response to IL-3 [37].

Regulatory relationships of Il3

• We demonstrate here that BSF-1 mRNA is expressed by a majority of transformed mast cell lines and by 5 IL-3-dependent non-transformed mast cell lines [22].
• These studies indicate that the IL-3 family of ligands is able to activate multiple isoforms of the signal transducing protein Stat5 [38].
• Furthermore IFN-gamma stimulated an increase in the number of macrophages present in colonies formed in the presence of IL-3 [39].
• Erythropoietin receptor haploinsufficiency and in vivo interplay with granulocyte-macrophage colony-stimulating factor and interleukin 3 [40].
• IL-3 induces phosphorylation of the above proteins with the exception of mpl and also causes weak JAK1 phosphorylation [41].

Other interactions of Il3

• Antigen-specific secretion of IL-2, IL-3, and IL-4 by in vivo effectors was detectable by 12 hours following in vitro restimulation [42].
• Interleukin-3 signals through multiple isoforms of Stat5 [38].
• Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors [43].
• We used reverse transcriptase polymerase chain reaction to assay the c-kitBR subset and the subsets expressing low (c-kitDULL) and no (c-kitNEG) c-kit receptor for expression of mRNA encoding hematopoietic growth factor receptors and transcription factors [44].
• Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor [45].
• These data indicate for the first time that 24p3 is a Foxo3a target gene and that PI3K/Akt (but not MAPK) mediates IL-3-regulated 24p3 expression in hematopoietic cells [46].

Analytical, diagnostic and therapeutic context of Il3

• After 7 days of coculture with virus-producing cells, bone marrow cells were plated in methylcellulose culture in the presence of EPO, interleukin-3, or Steel factor alone or in combination [47].
• Biologic assays failed to detect IL 1 or IL 3 activity in 95/1.7 CM [48].
• Polymerase chain reaction amplification of cDNA made with reverse transcriptase from stromal RNA using two separate sets of IL-3-specific primers shows the presence of IL-3 message in irradiated stromal cells, which is only detectable with this more sensitive technique [49].
• Secondly, we determined the protection from apoptosis afforded by these cytokines, using electrophoretic analysis of DNA and by flow cytometry of FL cells deprived in culture of epo, IL-3, and SCF [50].
• No rearrangements of the IL-3 or GM-CSF genes were observed by Southern blot analysis [3].

References