Disease relevance of Il5

• The reduced IL-5 production in IL-4-/- mice correlated with reduced helminth-induced eosinophilia, which has been shown to be dependent on IL-5 in vivo [1].
• Interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor are hematopoietic growth factors that increase the survival of eosinophils in culture and enhance certain eosinophil functions, such as mediator generation and toxicity [2].
• T cell line, mastocytoma cell line, or macrophage tumor cell line did not display detectable levels of IL-5-R. were hardly detectable on normal resting B cells but were expressed on LPS-activated B cells, fitting the function of IL-5 that acts on activated B cells for their differentiation into Ig-secreting cells [3].
• Mechanisms regulating the mRNA levels of interleukin-5 and two other coordinately expressed lymphokines in the murine T lymphoma EL4.23 [4].
• Defective expression of granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5 receptor common beta chain in children with acute myeloid leukemia associated with respiratory failure [5].

High impact information on Il5

• T helper 2 (T(H)2) cells elaborate cytokines, such as interleukin (IL)-4, IL-5, IL-9 and IL-13, which work with toxic mediators of innate immune cells to establish environments that are inhospitable to helminth or arthropod invaders [6].
• Interleukin-5 (IL-5) is a lineage-specific cytokine for eosinophilpoiesis and plays an important part in diseases associated with increased eosinophils, such as asthma [7].
• The structure of IL-5 provides a molecular basis for the design of antagonists and agonists that would delineate receptor recognition determinants critical in signal transduction [7].
• We have previously reported that IL-5-stimulated B cells are induced to express the 55K chain [8].
• To elucidate the molecular properties of TRF we isolated cDNA encoding TRF from the 2.19 T-cell line and report here the structure and multiple activities of this lymphokine [9].

Chemical compound and disease context of Il5

• In this report, we have performed transient transfection experiments with IL-5 promoter-reporter gene constructs, DNase I footprinting assays, and electrophoretic mobility shift assays to investigate the key regulatory regions necessary for activation of the IL-5 promoter by dibutyryl cAMP and phorbol esters in the mouse thymoma line EL-4 [10].
• In spleen cells from Mycobacterium tuberculosis-primed mice, significant expression of TRF/IL-5 mRNA was detected only when the cells were stimulated with relevant Ag, PPD [11].
• Anti-IL-5 treatment during RSV infection reduced AHR and lung eosinophilia after subsequent exposure to allergen [12].
• Effects of cyclosporin A and dinactin on T-cell proliferation, interleukin-5 production, and murine pulmonary inflammation [13].
• This study describes the identification of R146225, a novel six-substituted azauracil derivative, as a potent, orally active inhibitor of IL-5 biosynthesis, capable of reducing pulmonary eosinophilia in mice [14].

Biological context of Il5

• Interleukin 5 induces S mu-S gamma 1 DNA rearrangement in B cells activated with dextran-anti-IgD antibodies and interleukin 4: a three component model for Ig class switching [15].
• The biological effects of IL-5 were mediated by high-affinity binding sites [3].
• Together, our data show that T-cell receptor-mediated and lymphokine receptor-mediated signals induce different patterns of lymphokine gene expression and provide strong evidence that the IL-4 and IL-5 genes are differently regulated [16].
• CD38 ligation induces tyrosine phosphorylation of Bruton tyrosine kinase and enhanced expression of interleukin 5-receptor alpha chain: synergistic effects with interleukin 5 [17].
• A critical cytoplasmic domain of the interleukin-5 (IL-5) receptor alpha chain and its function in IL-5-mediated growth signal transduction [18].

Anatomical context of Il5

• Another well-characterized B-cell factor is T-cell replacing factor (TRF), which, when secreted by the murine T-cell hybridoma B151K12, is defined by two activities: induction of IgM secretion by BCL1 leukaemic B-cell line; and induction of secondary anti-dinitrophenol (DNP) immunoglobulin G (IgG) synthesis in vitro by DNP-prime B cells [9].
• However, these CD8- cells produced large amounts of IL-4, IL-5, and IL-10 and helped activate resting B cells [19].
• 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 [2].
• Bone marrow from transgenic mice was rich in IL-5-dependent eosinophil precursors [20].
• IL-5 mRNA was detected in transgenic thymus, Peyer's patches, and superficial lymph nodes, but not in heart, liver, brain, or skeletal muscle or in any tissues from nontransgenics [20].

Associations of Il5 with chemical compounds

• IL-5 also supported formation of both multi-lineage and blast cell colonies from dormant progenitors of the 5-fluorouracil-treated transgenic mice [21].
• Effects of cyclosporine A and the protein synthesis inhibitors cycloheximide and anisomycin on IL-4 and IL-5 gene expression suggest that these genes are activated by different pathways after anti-CD3 stimulation [16].
• CD38 ligation on mouse B cells by CS/2, an anti-mouse CD38 mAb, induced proliferation, interleukin 5 (IL-5) receptor alpha chain expression, and tyrosine phosphorylation of Bruton tyrosine kinase (Btk) from wild-type, but not from X chromosome-linked, immunodeficient mice [22].
• 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 [4].
• Only IL-5 enhanced IgA secretion in lipopolysaccharide-activated B cells and this response was increased two- to three-fold by IL-4 [23].

Physical interactions of Il5

• In mice, the alpha subunit (IL-5R alpha) specifically binds IL-5 with low affinity [24].
• Interleukin 2- and interleukin 5-induced changes in the binding of regulatory factors to the J-chain gene promoter [25].
• 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 [26].
• T cell-replacing factor co-purified with TCGF [27].
• Major histocompatibility complex regulation of interleukin-5 production in the mouse [28].

Regulatory relationships of Il5

• In contrast, IL-5 did not affect steady state levels of germline transcripts stimulated by IL-4, but did markedly increase levels of productive gamma 1 and epsilon transcripts [29].
• Conversely, the cells from the IL-3-induced blast cell colonies of the transgenic mice proliferated in response to either IL-3 or IL-5 [21].
• Multi-colony stimulating activity of interleukin 5 (IL-5) on hematopoietic progenitors from transgenic mice that express IL-5 receptor alpha subunit constitutively [21].
• In contrast, recombinant IL-2 induced IL-5 mRNA expression but did not induce detectable expression of IL-4 or granulocyte-macrophage colony-stimulating factor mRNA [16].
• These data imply that Lyn is involved in B cell triggering by CD38 ligation plus IL-5 for isotype switching [22].
• These results suggest that IL-5-induced hypereosinophilia could suppress sensitization to Ag via a TGF-beta-dependent mechanism, thus suppressed allergic airway inflammation [30].

Other interactions of Il5

• Furthermore, IL-10-/- outbred mice exhibited exaggerated airway inflammation and heightened levels of IL-5 and IFN-gamma in bronchoalveolar lavage (BAL) fluids [31].
• These results suggest that IL-4, IL-5, and IL-2 cooperate in the regulation of B lymphocyte Ig isotype expression [32].
• Moreover, IL-5 was found to be an eosinophil chemotactic factor by the checkerboard assay [33].
• These results strongly suggest that the lineage specificity of IL-5 is mainly due to the restricted expression of IL-5R alpha [21].
• Interleukin-3, granulocyte-macrophage colony stimulating factor and interleukin-5 transduce signals through two STAT5 homologs [34].

Analytical, diagnostic and therapeutic context of Il5

• Using in situ hybridization, the presence of IL-5 mRNA has been demonstrated in bronchial biopsies from asthmatic subjects [2].
• The recent molecular cloning of the complementary DNA encoding T cell--replacing factor (TRF) has demonstrated that a single molecule is responsible for B cell growth factor II (BCGF-II) activity and eosinophil differentiation activity [33].
• Stimulation of B cells with IL-5 together with CD38 ligation induces not only IgM but also IgG1 secretion [22].
• Gene microarray analysis reveals interleukin-5-dependent transcriptional targets in mouse bone marrow [35].
• The TRF and TCGF activities had a m.w. of 35,000 to 40,000 on gel filtration in phosphate-buffered saline (PBS) [36].

References