Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-5 (IL-5) and IL-6 have both been reported to act as B-cell differentiation factors by stimulating activated B cells to secrete antibody. However, it has not been possible to directly compare the effects of these two lymphokines because of the lack of a suitable B-cell line capable of responding to both. We have identified a clonal, inducible B-cell lymphoma, CH12, that has this property. Both IL-5 and IL-6 can independently stimulate increases in steady-state levels of immunoglobulin and J-chain mRNA and proteins, and they both induce the differentiation of CH12 into high-rate antibody-secreting cells. Nevertheless, there are significant differences in the activities of these two lymphokines. First, while IL-6 acts only as a differentiation factor, IL-5 also augments the proliferation of CH12 cells. Second, the differentiation stimulated by IL-5 but not by IL-6 is partially inhibited by IL-4. Inhibition of IL-5-induced differentiation was not at the level of IL-5 receptor expression, since IL-4 did not inhibit IL-5-induced proliferation. Third, IL-5 but not IL-6 stimulated increased mouse mammary tumor proviral gene expression in CH12 cells. These results demonstrate that while both IL-5 and IL-6 may act as differentiation factors for B cells, they induce differentiation by using at least partially distinct molecular pathways. Our results also establish that B cells characteristic of a single stage of development can independently respond to IL-4, IL-5, and IL-6.
Mol Cell Biol 1993 Jul
PMID:Interleukin-5 (IL-5) and IL-6 define two molecularly distinct pathways of B-cell differentiation. 832 Dec

To investigate the mechanism of eosinophilia in patients with eosinophilic pleural effusions, we measured the activities of eosinophil colony-stimulating factor (Eo-CSF) and stimulating factor for eosinophil survival in the eosinophilic pleural fluids of six patients (two with tuberculous pleuritis, two with drug allergy, and one each with chronic eosinophilic pneumonia and pleuritis associated with rheumatoid arthritis). The number of eosinophil colonies formed by the pleural fluid of patients with eosinophilic pleural effusions significantly exceeded that of control patients with noneosinophilic pleural effusions (7.5 +/- 1.9 colonies/10(5) bone marrow cells, n = 6, versus 0.3 +/- 0.1 colonies/10(5) bone marrow cells, n = 6, P < 0.01). Similarly, eosinophil survival evaluated on day 4 of culture with pleural fluid of patients with eosinophilic pleural effusions significantly exceeded that of patients with noneosinophilic pleural effusions (83.9 +/- 9.8% versus 46.1 +/- 11.2%, P < 0.001). Both activities were inhibited mainly by anti-IL-5 antibody and partially by anti-GM-CSF antibody and anti-IL-3 antibody. Mononuclear cells obtained from eosinophilic pleural fluid released the activities of Eo-CSF and stimulating factor for eosinophil survival in vitro. These findings suggest that GM-CSF, IL-5, and IL-3 are important to eosinophil accumulation in pleural cavity as stimulators of proliferation and survival of eosinophils.
Am J Respir Cell Mol Biol 1993 Jun
PMID:Factors that stimulate the proliferation and survival of eosinophils in eosinophilic pleural effusion: relationship to granulocyte/macrophage colony-stimulating factor, interleukin-5, and interleukin-3. 832 45

A panel of steady-state cytokine mRNAs was analyzed in the bronchoalveolar lavage (BAL) cells from asthmatic subjects or patients challenged with ragweed allergen. This was achieved by combining both qualitative and quantitative assays using the reverse transcription-polymerase chain reaction (RT-PCR). Analysis of BAL cells from six mild allergic asthmatic and five nonasthmatic, nonallergic subjects showed no qualitative differences in the profile of cytokine mRNAs (including interleukin [IL]-1 beta, IL-2, IL-5, IL-6, IL-8, and granulocyte/macrophage colony-stimulating factor), except for tumor necrosis factor-alpha, which was detected in three out of six asthmatic BAL samples but in none of the controls. A key cytokine, IL-5, has been implicated in the pathogenesis of allergic inflammation through the recruitment of eosinophils. We found a significant enhancement of steady-state IL-5 transcripts in the BAL cells from allergen-challenged as compared with the saline-challenged control sites of four asthmatic patients; furthermore, the cellular source for IL-5 mRNA was identified in the mononuclear cell fraction, but not in the purified eosinophils, of the allergen-challenged BALs. These results suggest that the significant increase of IL-5 transcripts is primarily from the infiltrating mononuclear cells. Our study also demonstrates the power of qualitative and quantitative PCR analysis in determining the molecular basis of allergic inflammatory diseases.
Am J Respir Cell Mol Biol 1993 Sep
PMID:Analysis of cytokine transcripts in the bronchoalveolar lavage cells of patients with asthma. 839 65

We have investigated the phenotype of interleukin-5 (IL-5) mRNA+ cells in the nasal mucosa of subjects with allergic rhinitis. Serial cryostat sections were cut from paraformaldehyde-fixed snap-frozen nasal biopsies from six patients, before and 24 h after local allergen provocation with grass pollen. Immunocytochemistry (APAAP) was followed by in situ hybridization on the same sections. For immunocytochemistry, antibodies against CD3, tryptase, and major basic protein (MBP) were used to identify T cells, mast cells, and eosinophils, respectively. Hybridization studies were performed using a Digoxigenin-labeled IL-5 riboprobe. Nitroblue tetrazolium (NBT) and X-phosphate-5-bromo-4-chloro-3- indoly phosphate (BCIP) served as chromogens to detect hybridized IL-5 mRNA signals. The majority of IL-5 mRNA+ cells were CD3+ (83.2%), whereas the remainder were either tryptase+ (11.3%) or MBP+ (5.4%). In contrast, only a few IL-5 mRNA+ cells were observed in nasal biopsies before challenge, all of which were co-localized to CD3+ cells. These results indicate that CD3+ cells are the principal cellular source of IL-5 transcripts in the nasal mucosa 24 h after allergen-induced late-phase nasal responses.
Am J Respir Cell Mol Biol 1993 Oct
PMID:T cells are the principal source of interleukin-5 mRNA in allergen-induced rhinitis. 839 74

We investigated the effects of Dermatophagoides farinae (Df) and interleukin (IL)-2 on the release of eosinophil colony-stimulating factor (Eo-CSF) activity from mononuclear cells (MNC) and lymphocytes of patients with bronchial asthma (BA) who were sensitive to Df to clarify its relationship with IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF). MNC and T cells of patients cultured with IL-2 and Df released Eo-CSF activity. These Eo-CSF activities were partially inhibited by anti-IL-5 and anti-GM-CSF antibodies. In 11 of 15 cases studied, MNC from patients produced GM-CSF in response to IL-2. In four of 15 cases studied, MNC from patients produced GM-CSF in response to Df. On culture with IL-2 or Df, the releases of IL-5 into the medium by MNC from individual patients varied. The results indicate that in BA responsiveness of lymphocytes to Df is increased, and suggest that IL-5 and GM-CSF produced by T cells play a role in the induction of eosinophilia and the pathogenesis of BA.
Am J Respir Cell Mol Biol 1993 Oct
PMID:Production of interleukin-5 and granulocyte/macrophage colony-stimulating factor by T cells of patients with bronchial asthma in response to Dermatophagoides farinae and its relation to eosinophil colony-stimulating factor. 839 76

Immunohistology and in situ hybridization were used to evaluate the presence, activation status, and cytokine mRNA profile of cells in the bronchial mucosa during human allergen-induced asthma. Fifteen atopic asthmatic subjects underwent inhalation challenge with allergen and with allergen diluent, performed in random order separated by an interval of at least 3 wk. Bronchial biopsies were obtained 24 h after challenge. Immunostaining revealed increases in the numbers of secreting eosinophils (EG2+; P < 0.05) and in interleukin-2 receptor (IL-2R)-positive cells (CD25+; P < 0.01) after allergen compared with diluent challenge. No differences were observed in the numbers of total leukocytes (CD45+), T lymphocytes (CD3+, CD4+, and CD8+), elastase-positive neutrophils, macrophages (CD68+), or mast cell subtypes (MCT+ or MCTC+). In situ hybridization revealed significant increases in the numbers of cells expressing mRNA for IL-5 (P < 0.02) and granulocyte/macrophage colony-stimulating factor (P < 0.01) after allergen compared with diluent challenge. A significant inverse relationship was observed between the number of cells expressing mRNA for IL-4 and for interferon-gamma (r = -0.75, P < 0.02). The results support the view that cytokines possibly from activated T lymphocytes may contribute to local eosinophil accumulation during allergen-induced asthma.
Am J Respir Cell Mol Biol 1993 Jan
PMID:Increases in activated T lymphocytes, eosinophils, and cytokine mRNA expression for interleukin-5 and granulocyte/macrophage colony-stimulating factor in bronchial biopsies after allergen inhalation challenge in atopic asthmatics. 841 55

Recombinant human interleukin-5 (rhIL-5) has been crystallized by the hanging drop vapor diffusion method using 0.1 M-Tris.HCl buffer (pH 8.5) containing 0.2 to 0.25 M-sodium acetate and 26 to 30% PEG 4000 at 22 degrees C. The parallel-piped crystals belong to the space group C2 with unit cell dimensions of a = 122.1 A, b = 36.11 A, c = 56.42 A, beta = 98.59 degrees. They diffract to at least 2.0 A resolution on a rotating anode X-ray source. The molecular mass weight of the protein and the volume of the unit cell suggest that the asymmetric unit contains one intermolecular disulfide-bonded homodimer.
J Mol Biol 1993 Feb 20
PMID:Crystallization and preliminary X-ray diffraction studies of recombinant human interleukin-5. 844 40

The ability of the sex hormones progesterone, testosterone and estradiol-17 beta and the glucocorticoid dexamethasone to modulate expression of the interleukin-5 (IL-5) gene in T cell lines has been investigated. The T cell lines used show analogous regulation of IL-5 gene expression to that occurring in T-lymphocytes, in that IL-5 mRNA levels are undetectable unless the cells are induced with phorbol myristate acetate (PMA). Progesterone and testosterone were as effective as PMA in inducing IL-5 mRNA levels in the T cell hybrid NIMP-TH1 and induced IL-5, -3 and -2 mRNA accumulation in the T cell lymphoma EL-4. Estradiol-17 beta also induced IL-5 mRNA accumulation but less effectively than testosterone. Nuclear run-on experiments suggested that the effects of progesterone, testosterone and PMA on IL-5 gene expression were mediated at the level of transcription. The presence of the protein synthesis inhibitor cycloheximide completely prevented PMA-induced synthesis of IL-5 mRNA by both NIMP-TH1 and EL-4 cells, indicating that induction of IL-5 mRNA via PMA stimulation requires de novo synthesis of a presumptive trans-acting factor(s). PMA-, testosterone- and progesterone-induced expression of the IL-5 gene was completely blocked by the anti-inflammatory steroid dexamethasone. Stimulation of IL-5 expression by PMA was relatively resistant to the immuno- suppressive drug cyclosporin A although inhibition did occur at very high levels. Testosterone- and progesterone-induced IL-5 gene expression was not inhibited by cyclosporin A. The in vivo significance of these findings are not yet clear but the results show that sex hormones have the potential to regulate cytokine gene expression in cells possessing the appropriate steroid receptors.
J Steroid Biochem Mol Biol 1993 Mar
PMID:Sex hormones and dexamethasone modulate interleukin-5 gene expression in T lymphocytes. 846 Dec 54

As with other types of leukocytes, mechanisms that function to enable the recruitment of eosinophils into specific sites of immune reactions involve a complex and cumulative interplay of many molecules and pathways. No single chemoattractant is specific for eosinophils, but rather various chemoattractants active on eosinophils can also elicit migration of other specific cell types. Humoral mediators causing eosinophil migration include C5a and platelet-activating factor, whereas cytokines active as eosinophil chemoattractants include interleukin (IL)-2, IL-3, IL-5, granulocyte/macrophage colony-stimulating factor, lymphocyte chemoattractant factor, and RANTES. Eosinophils utilize several pathways to adhere to vascular endothelial cells, including binding to intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 (VCAM-1). The lack of binding of neutrophils to VCAM-1 and the enhanced expression of VCAM-1 elicited by IL-4 contribute to preferential eosinophil accumulation. Eosinophil recruitment is dependent not only on ligands expressed on eosinophils and molecules inducible on endothelial cells but also on processes active during transendothelial migration and extravascular migration in the extracellular spaces.
Am J Respir Cell Mol Biol 1993 Apr
PMID:Mechanisms of eosinophil recruitment. 847 27

Chronic graft-versus-host disease (GVHD) can be induced in B6D2F1 mice by injection of parental DBA/2 lymphoid cells. Stimulation of donor T cells by host MHC antigens leads to the stimulation of host B cells. Little is known of the lymphokines produced during such a reaction. This study was designed to directly measure the levels of mRNA for interferon-gamma (IFN-gamma), interleukin 2 (IL-2), IL-4, IL-5, and IL-10, as well as several other genes, using semiquantitative polymerase chain reaction (PCR). Semiquantitative PCR was reproducible and signals generated were dependent on the amount of specific RNA or cDNA in each reaction. Early during the progression of GVHD (2 days after the first injection of parental cells) there was little increase in IL-10 mRNA, a slight increase in IL-4 mRNA, and a dramatic increase in IL-2 mRNA. In addition, IL-2 bioactivity was demonstrated in supernatants from GVH splenocytes cultured in vitro for 24 h. Later in the response (1 week after the second and final injection of parental cells) IL-4 mRNA levels were elevated as they were earlier while IL-10 mRNA levels were dramatically increased. IL-2 mRNA levels were no different in mice undergoing GVHD than in normal mice at this time. IFN-gamma mRNA was detectable both early and late, although at similar levels in normal mice and mice undergoing GVHD. At both times examined, IL-4 was below the limits of detection by bioassay and IFN-gamma, IL-4, IL-5 and IL-10 were below the limits of detection by ELISA. Further studies showed that a majority of the IL-4 and IL-10 mRNA found elevated in GVH mice were produced by Thy1.2+ T cells, with small amounts from B220+ B cells. In addition, the detectable IFN-gamma mRNA found in GVH mice at this later time also was produced by Thy1.2+ T cells, with small amounts from B220+ B cells.
Mol Immunol 1993 May
PMID:Cytokine gene expression in mice undergoing chronic graft-versus-host disease. 848 82


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