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

Recent advances of T cell cloning have allowed the classification of T helper cells in terms of the lymphokines they secrete. The functional significance of segregating lymphokine production to unique T cell subsets is still being evaluated, but undoubtedly plays a key role in the regulatory mechanisms of the immune system. Initial studies have indicated that the Th1 cells which secrete IL-2 and IFN-gamma may be primarily responsible for augmenting cell-mediated responses, whereas Th2 cells, which release IL-4, IL-5, and IL-6, provide help for humoral responses. However, it is also known that B cells can respond to both IL-2 and IFN-gamma. This raises the question of the homogeneity of B lymphocyte activation requirements. Are all B cells responsive to all of the lymphokines with the end-result of stimulation depending largely on the relative concentrations of the various lymphokines, or are there B cell subsets which only respond to Th1-derived lymphokines and others which respond to Th2-derived lymphokines? Such differential activation requirements might be present to allow these subsets to play unique roles in immunological responses. Since B cell cloning techniques have not yet been developed to obtain a homogenous B cell population for studies of activation requirements, regulation of lymphokine receptors, and regulation of gene expression, we must utilize lymphokine-responsive neoplastic B cells. The vast majority of spontaneous B cell lymphomas appear to belong to a minor B cell subset which expresses the Ly1 marker. This subset is clearly not representative of the majority of splenic B cells.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Immunol 1990
PMID:Characterization of a neoplastic B cell clone that secretes IgM in response to Th2-derived lymphokines. 215 Apr 85

Systemic administration of interleukin (IL)-2 to patients with malignant diseases induces peripheral eosinophilia. In the present study, to clarify the mechanism of eosinophilia induced by IL-2, we examined the changes in the number of eosinophils and eosinophil colony-stimulating factor (Eo-CSF) activity in the pleural fluids of six patients with malignant pleurisy caused by lung cancer or malignant mesothelioma during and after intrapleural administration of IL-2. Results showed that intrapleural administration of IL-2 induced marked eosinophilia in the pleural fluid and moderate eosinophilia in the peripheral blood, and that during IL-2 administration, marked Eo-CSF activity appeared in the pleural fluid before increase in the number of eosinophils, but that this activity did not appear in the peripheral blood. This Eo-CSF activity was inhibited by a combination of anti-IL-5 antibody, anti-IL-3 antibody, and anti-granulocyte/macrophage colony-stimulating factor (anti-GM-CSF) antibody, but not by each antibody alone. Chemotactic activity for eosinophils was also detected in the pleural fluid during IL-2 treatment. These results suggest that eosinophilia in the pleural fluid induced by IL-2 injection into the pleural cavity of patients with malignant pleurisy is due to the Eo-CSF activities of various components, including IL-5, IL-3, and GM-CSF, and chemotactic factors for eosinophils induced locally in the pleural cavity by IL-2.
Am J Respir Cell Mol Biol 1990 Oct
PMID:Eosinophil colony-stimulating factor induced by administration of interleukin-2 into the pleural cavity of patients with malignant pleurisy. 220 37

T-cell-replacing factor (TRF)/IL-5 is a T-cell-derived glycoprotein which has pleiotropic activity on lymphoid and myeloid cells. IL-5 polypeptide translated into Xenopus oocytes are heterogeneous in molecular size (40,000 to 60,000 under nonreducing conditions) and yields a monomeric form (Mr of 25,000 to 30,000) under reducing conditions (J. Immun., 140, 1175-1181, 1988). We purified T-cell-derived TRF and rIL-5 using anti-TRF/IL-5 antibody-coupled affinity column from supernatants of a T-cell hybridoma B151K12 and supernatants of HeLa cells, respectively, which had been transfected with murine IL-5 cDNA, and determined their partial N-terminal amino acid sequence (27 residues for B151-TRF and 13 residues for rIL-5). A single amino acid sequence of each sample obtained beginning from methionine that was identical to that predicted from IL-5 cDNA. This finding supports the notion that secreted B151-TRF polypeptide consists of 113 amino acids. Purified B151-TRF supported eosinophilopoiesis of human bone marrow cells as effective as mouse rIL-5 and human rIL-5. B151-TRF competitively inhibited 35S-labeled rIL-5 binding to target cells to the same extent at rIL-5. Treatment of purified rIL-5 and B151-TRF with reducing reagents such as 2-ME, sodium borohydride or dithiothreitol produced a monomeric form of IL-5 which did not exert a biological activity. Reduction and alkylation of rIL-5 caused the loss of binding to its target cells. These results strongly suggest that B151-TRF exists as a homodimer and its primary structure and secondary structures are identical to those of rIL-5. Moreover, the formation of inter-molecular disulfide bond(s) linked by two pairs of cystein residues is essential for the expression of the biological activity of mouse IL-5.
Mol Immunol 1990 Sep
PMID:Structural comparison of murine T-cell (B151K12)-derived T-cell-replacing factor (IL-5) with rIL-5: dimer formation is essential for the expression of biological activity. 221 80

A conserved DNA sequence element, termed cytokine 1 (CK-1), is found in the promoter regions of many hemopoietic growth factor (HGF) genes. Mutational analyses and modification interference experiments show that this sequence specifically binds a nuclear transcription factor, NF-GMa, which is a protein with a molecular mass of 43 kilodaltons. It interacts with different affinities with the CK-1-like sequence from a number of HGF genes, including granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte (G)-CSF, interleukin 3 (IL-3), and IL-5. We show here that the level of NF-GMa binding is induced in embryonic fibroblasts by tumor necrosis factor-alpha (TNF-alpha) treatment and that the CK-1 sequence from the G-CSF gene is a TNF-alpha-responsive enhancer in these cells. The NF-GMa protein is distinct from another TNF-alpha-responsive transcription factor, NF-kappa B, by several criteria. Firstly, several NF-kappa B-binding sites, although having sequence similarity with the CK-1 sequence, cannot compete efficiently for NF-GMa binding to CK-1. Secondly, the CK-1 sequence from both G-CSF and GM-CSF does not respond to phorbol ester treatment as would an NF-kappa B-binding element. These results demonstrate that NF-GMa is a novel transcription factor inducible by TNF-alpha and binds to a common element in HGF gene promoters.
Mol Cell Biol 1990 Jun
PMID:A novel tumor necrosis factor-responsive transcription factor which recognizes a regulatory element in hemopoietic growth factor genes. 234 64

The murine IL-4 and IL-5 genes encode hemopoietic growth factors involved in the stimulation, proliferation, and differentiation of cells of the T lymphocyte, B lymphocyte, and granulocyte lineages. We have mapped the Il-4 and Il-5 loci representing the structural genes for IL-4 and IL-5, respectively, to mouse chromosome 11 using Chinese hamster x mouse and rat x mouse somatic cell hybrids. Physical linkage studies of the IL-4 and IL-5 genes by pulsed field gel electrophoresis have shown that they are closely linked, being 110-180 kb apart. Since the Il-5 locus maps to the interface of bands A5 and B1 in the same location as the genes for IL-3 and GM-CSF, this places these three cytokine genes, as well as the IL-4 gene, within a region of about 5000-10,000 kb. The present physical linkage studies indicate that the IL-4 and IL-5 genes are a minimum of 600 kb apart from the closely linked IL-3 and GM-CSF genes. The gene clustering, together with similarities in gene structure, regulation, and biological function, raises the possibility that the four genes may be part of a distantly related cytokine gene family.
Somat Cell Mol Genet 1989 Mar
PMID:The IL-4 and IL-5 genes are closely linked and are part of a cytokine gene cluster on mouse chromosome 11. 278 91

B cells can be activated by T-independent antigens or mitogens such as lipopolysaccharide (LPS) which will induce proliferation and differentiation of the B cells into Ig-secreting cells, without the intervention of T cells. The precise mechanism of T-independent proliferation and differentiation of B cells is still unclear. It is possible however that antigen-stimulated B cells may produce some factors which play a role in T-independent B-cell responses. In addition, since it has now been established that B cells can function as antigen-presenting cells, it is possible that they too secrete a molecule which is involved in the activation of T cells, analogous to IL-1 production by antigen-presenting macrophages. A number of human B-cell lines, as well as human normal B cells activated appropriately, have been shown to produce various cytokines, and similar studies are now being undertaken in the mouse. In the present study, six cloned murine B-cell lymphomas of different origin were analyzed for the presence of mRNA encoding a number of lymphokines by hybridization of specific cDNA probes to poly-A RNA, followed by the sensitive S1 nuclease digestion technique. The lymphokines included (IL-) 1, 2, 3, 4, 5, and neuroleukin. Whereas none of the lines expressed detectable levels of IL-2, IL-3, or IL-5 mRNA, all the lines expressed high levels of neuroleukin mRNA. Three of the lymphomas (CH12, CH31, and NBL) expressed low levels of IL-1 mRNA. The most striking finding was that one lymphoma, CH12, constitutively expressed IL-4 mRNA. This mRNA appeared to be functional, as IL-4 activity measured by the HT-2 T cell proliferation assay could be detected in supernatants collected from CH12 cells. The growth-inducing activity of CH12 supernatant on HT-2 cells could be completely blocked by an anti-IL-4 monoclonal (11B11), but not by an anti-IL-2 antibody (S4B6), consistent with our observations that CH12 cells produce IL-4 but not IL-2. CH12 cells were also found to express high affinity receptors for IL-4. Proliferation of CH12 cells was not affected by the addition of exogenous IL-4. Addition of anti-IL-4 antibodies to CH12 cells in culture caused a slight but reproducible increase in their proliferation at low cell numbers, which is probably not highly significant. These findings open the possibilities that murine B lymphocytes are capable of lymphokine production or alternatively that aberrant lymphokine production underlies B-lymphocyte transformation.
J Mol Cell Immunol 1989
PMID:Constitutive production of lymphokines by cloned murine B-cell lymphomas--CH12 B lymphoma produces interleukin-4. 278 29

We have analyzed the pattern of immunoglobulin (Ig) heavy chain isotype secretion in AJ9, a cloned, IgM+ murine B lymphocyte cell line. Upon induction by a variety of lymphokines and polyclonal B-cell activators, AJ9 cells express multiple subclasses of IgG and IgA in addition to IgM. In certain cases, mature isotype is restricted--e.g., IL-5 predominantly elicits production of IgG2 and IgA, a restriction also observed in short-term lymphocyte cultures. In other cases (e.g., anti-IgM plus 8-mercaptoguanosine, a polyclonal B-cell activator) production of mature isotypes is unrestricted. Under optimal conditions, only a low abundance of secreted Ig and low frequency of secreting cells (less than 0.5%) were detected. A serial cloning assay was devised to define the pattern of isotype switching in induced cells and their progeny. We expected to observe a progressive limitation of progeny to expression of single mature isotypes. Surprisingly, nearly all subclones of the induced cells were found to produce a range of mature isotypes. Sequential cloning in basal medium revealed that this induced phenotype persisted for more than a month (greater than 40 generations). Throughout this period, the abundance of mature isotype production remained low, and membrane Ig was exclusively of the IgM isotype. We interpret this induced response to reflect an intermediate state of B-cell differentiation, in which cells become committed to the switching process, but are not adequately stimulated to efficiently complete the process required for expression of mature isotypes. These findings are discussed in regard to the control of the switching process, and their possible relevance to the memory state of B cells.
J Mol Cell Immunol 1988
PMID:Inducible Ig heavy chain switching in an IgM+ Ly-1 B cell line. Evidence for a state of switch commitment. 315 Dec 47

A synthetic DNA construct has been developed as a standard molecule whereby murine cytokine mRNA molecules can be quantified by the reverse transcription-polymerase chain reaction (RT-PCR). The construct, designated Cytoquant 1, allows the quantification of murine IL-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IFN-gamma, TNF-alpha, TGF-beta, GM-CSF, CD4, CD8, HPRT and beta-actin mRNA levels. This technique is based on the amplification of a transcribed RNA molecule from Cytoquant 1 as an internal standard control in both the RT and PCR reactions. The quantification data from these analyses are expressed in absolute values, i.e. molecules/cell, which allows the data derived from separate experiments to be compared. In this study, mRNAs encoding beta-actin, IL-10, IFN-gamma and GM-CSF have been quantitated in both Th1 and Th2 cell clones with, and without, stimulation. The quantitative analysis data are highly reproducible and cytokine mRNA concentrations are reflective of restricted cytokine secretion patterns. Furthermore, constitutive cytokine mRNA levels are detectable in resting cells, eliminating the need for exogenous stimulation. The high degree of sensitivity and accuracy make this methodology uniquely suited for the study of T-cell subset cytokine expression in both in vivo and in vitro biological models.
Mol Immunol 1995 Sep
PMID:A synthetic standard DNA construct for use in quantification of murine cytokine mRNA molecules. 747 5

A murine pulmonary infection model utilizing intratracheal inoculation of Cryptococcus neoformans was used to analyze cytokines produced in response to opportunistic pathogens acquired via the respiratory tract. The specific question asked was whether early cytokine secretion in lung-associated lymph nodes (LALN) would predict whether this organism would be cleared from the lung. Lung colony-forming units (CFU) were analyzed in two strains of mice over 12 wk, and lung clearance was found to be strain dependent. C.B-17 mice reduced their lung CFU burden between day 7 and day 14 of infection, had significantly higher in lung CFU than C.B-17 mice. The capacity of cells from lungs and LALN to secrete cytokines was significantly different between the strains when assessed at day 7 and day 14 after inoculation. When compared with sensitive C57BL/6 mice 7 days after infection, resistant C.B-17 mice demonstrated (1) increased interferon-gamma secretion by LALN cells in vitro in response to media alone, heat-killed cryptococci, and the T cell mitogen concanavalin A and (2) increased interleukin (IL)-2 secretion by both LALN and lung cells in response to concanavalin A. IL-4 and IL-10 were comparable or undetectable in both mouse strains, whereas IL-5 was significantly higher in all lung cell cultures of C57BL/6 mice. Thus, an early regional Th1 immune response in C.B-17 mice correlated with resistance to the organism, whereas the absence of this response in C57BL/6 mice correlated with susceptibility.
Am J Respir Cell Mol Biol 1995 Oct
PMID:Early cytokine production in pulmonary Cryptococcus neoformans infections distinguishes susceptible and resistant mice. 754 79

In nasal biopsies from 17 adult patients with seasonal allergic rhinitis and from 10 healthy controls, cytokines were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR). The time-course study during winter included repeated local allergen provocation with subsequent nasal biopsies as well as biopsies taken during pollen season. The RT-PCR for CD44 yielded positive bands in 65 of 71 cases, in which cases mRNA for interleukins 2, 4, and 5 (IL-2, IL-4, and IL-5) were thus investigated by means of seminested PCR. IL-4 mRNA was found almost exclusively in the allergic patients. During provocation a significant increase in IL-4 was noticed compared with controls (p = 0.043). Equally, during the natural pollen season, IL-4 mRNA expression was significantly higher in patients not using nasal corticosteroids compared with those who did (p = 0.011). No differences in IL-2 or IL-5 were observed between the groups. These findings also indicate, together with earlier observations of T-cell activation, a phenotype switch toward T-helper 2 (Th2) cells, and the accumulation (homing) of these T cells in the nasal mucosa, that T cells constitute the main source for IL-4 in the nasal mucosa. Therefore, allergic patients have an increased synthesis of IL-4 when provoked with the allergen, and during natural pollen season this synthesis can be downregulated by corticosteroids. Furthermore, this study exemplifies the versatility of molecular biology in surgical pathology and that even low-copy-number cytokine mRNA can be examined in routinely snap-frozen surgical specimens.
Diagn Mol Pathol 1995 Jun
PMID:Nasal messenger RNA expression of interleukins 2, 4, and 5 in patients with allergic rhinitis. 755 Dec 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>