Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This laboratory previously reported that mRNA expression for many cytokines, as determined by reverse transcription-polymerase chain reaction analysis, is induced rapidly in the spleen during murine listeriosis. In the present study, the patterns of cytokine mRNA expression in spleens and livers of Listeria-resistant C57BL/6 and Listeria-susceptible A/J mice were compared. In addition, in situ hybridization was performed to evaluate the distributions of cytokine mRNA-expressing cells in these tissues. Listeria-resistant C57BL/6 mice demonstrated greater expression of gamma interferon (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNAs in the spleen than Listeria-susceptible A/J mice. Greater numbers of cells expressing IFN-gamma and GM-CSF mRNAs were observed by in situ hybridization in the spleens of C57BL/6 mice than in those of A/J mice. C57BL/6 and A/J mice did not differ in their expression of IFN-gamma mRNA in the liver. Nor did C57BL/6 and A/J mice differ in their expression of tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha), IL-2, IL-4, or IL-6 mRNA in the liver or spleen, as determined by reverse transcription-polymerase chain reaction and in situ hybridization. These results indicate that the greater resistance of C57BL/6 mice to Listeria monocytogenes infection is associated with greater expression of IFN-gamma and GM-CSF mRNAs in the spleen and GM-CSF mRNA in the liver.
 ...
PMID:Analysis of cytokine mRNA expression in Listeria-resistant C57BL/6 and Listeria-susceptible A/J mice during Listeria monocytogenes infection. 835 95

Interferon-alpha (IFN-alpha) and IFN-gamma regulate gene expression by tyrosine phosphorylation of several transcription factors that have the 91-kilodalton (p91) protein of interferon-stimulated gene factor-3 (ISGF-3) as a common component. Interferon-activated protein complexes bind enhancers present in the promoters of early response genes such as the high-affinity Fc gamma receptor gene (Fc gamma RI). Treatment of human peripheral blood monocytes or basophils with interleukin-3 (IL-3), IL-5, IL-10, or granulocyte-macrophage colony-stimulating factor (GM-CSF) activated DNA binding proteins that recognized the IFN-gamma response region (GRR) located in the promoter of the Fc gamma RI gene. Although tyrosine phosphorylation was required for the assembly of each of these GRR binding complexes, only those formed as a result of treatment with IFN-gamma or IL-10 contained p91. Instead, complexes activated by IL-3 or GM-CSF contained a tyrosine-phosphorylated protein of 80 kilodaltons. Induction of Fc gamma RI RNA occurred only with IFN-gamma and IL-10, whereas pretreatment of cells with GM-CSF or IL-3 inhibited IFN-gamma induction of Fc gamma RI RNA. Thus, several cytokines other than interferons can activate putative transcription factors by tyrosine phosphorylation.
 ...
PMID:Tyrosine phosphorylation of DNA binding proteins by multiple cytokines. 839 44

The mycoplasmas are a diverse set of bacteria that, in the course of their interactions with cells of the immune system, have a wide range of immunomodulatory effects. These effects include polyclonal stimulation of proliferation of T and B lymphocytes; activation of cytolytic activity of macrophages, natural killer cells, and cytotoxic T cells; and stimulation of production of cytokines (interleukin [IL]-1, IL-2, IL-4, IL-6, interferon [IFN]-alpha, IFN-beta, IFN-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) by immunocompetent cells. Mycoplasmas have also been shown to induce major histocompatibility complex (MHC) expression in macrophage cell lines and cultures. This report demonstrates that induction of MHC expression by mycoplasmas is directly due to increases in the transcriptional activity of MHC genes. Experiments attempting to determine if the mechanism responsible for these increases in MHC expression requires the production of cytokines have demonstrated that production of IFN-gamma, IL-4, and GM-CSF is probably not involved.
 ...
PMID:Mycoplasmal induction of cytokine production and major histocompatibility complex expression. 839 13

Levels of cytokine mRNA were studied in the central nervous system (CNS) of SCID mice infected with Toxoplasma gondii. This infection led to 100% mortality by day 23 postinfection. Inflammation was observed in the lungs on day 7 and in the heart, liver, and kidneys on days 14 and 18 of infection. In the CNS, necrotic, acellular lesions that contained numerous parasites, accompanied by a localized astrocyte activation, were evident on day 14. Polymerase chain reaction-assisted amplification of RNA revealed that, although transcripts for interleukin-1 alpha (IL-1 alpha) and IL-1 beta were present in the brains of uninfected mice, increased levels of these transcripts were detected on day 7 of infection. Transcripts for macrophage inflammatory protein 1 and transforming growth factor beta were also detected in brains of infected mice at this time point. On days 14 and 18, levels of these transcripts had increased and transcripts for IL-6, IL-10, gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were also detected. Transcripts for IL-2 or IL-4 were not detected at any of the time points. Detection of locally produced cytokine transcripts may reflect involvement of the cytokines in the immunopathogenesis of this infection or involvement in mediating antitoxoplasma activity. To assess the possible role of endogenous IFN-gamma, TNF-alpha, IL-10, IL-6, and GM-CSF, cytokine-neutralizing monoclonal antibodies were administered to infected SCID mice. Neutralization of IFN-gamma or TNF-alpha led to earlier mortality than that in controls. In contrast, treatment with antibody to IL-10 and IL-6 increased survival time. Treatment with anti-GM-CSF did not alter the time to death. These results indicate that TNF-alpha and IFN-gamma are both involved in T-cell-independent mechanisms of resistance to T. gondii in SCID mice and that IL-10 and IL-6 may downregulate the immune response to this pathogen.
 ...
PMID:Cytokine mRNA in the central nervous system of SCID mice infected with Toxoplasma gondii: importance of T-cell-independent regulation of resistance to T. gondii. 840 91

The expression of cytokine genes in cultures of human peripheral blood mononuclear cells (PBMC) stimulated with mannoprotein constituents (MP) of Candida albicans has been studied by means of S1 nuclease mapping analysis, polymerase chain reaction, and enzyme-linked immunosorbent assay. MP induced early, consistent, and long-lasting production of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha, and IL-6 mRNAs. Similar results were obtained when the same PBMC cultures were stimulated with the purified protein derivative (PPD) from Mycobacterium tuberculosis or with IL-2, although lower levels of IL-6 mRNA were detected in IL-2-stimulated cells than in MP- or PPD-stimulated cells. MP, PPD, and IL-2 induced appreciable levels of granulocyte-macrophage colony-stimulating factor and gamma interferon, but only MP and PPD were able to induce IL-2 mRNA. MP were unable to stimulate a consistent expression of the genes encoding for IL-4, IL-5, and IL-10, while low, sometimes barely detectable levels of these cytokine mRNAs were observed in PPD- or IL-2-stimulated PBMC cultures. When protein synthesis of MP-stimulated PBMC was inhibited by cycloheximide, a superinduction of mRNAs for IL-4 and IL-10 and, more markedly, gamma interferon was observed. Overall, these results highlight the powerful, selective induction of cytokine gene expression by MP constituents of C. albicans in human PBMC cultures, thus providing some functional clues to explain the efficient state of the anticandidal response in normal human subjects.
 ...
PMID:Cytokine gene expression in human peripheral blood mononuclear cells stimulated by mannoprotein constituents from Candida albicans. 840 99

To gain insight into the functional capacity of human T cells in the immune response against Mycobacterium tuberculosis, we evaluated the spectrum of cytokines produced by mycobacterium-reactive human T-cell clones. Nine of 11 T-cell clones bearing alpha beta or gamma delta T-cell receptors produced both Th1 and Th2 cytokines, a pattern resembling that of murine Th0 clones. The most frequent pattern was secretion of gamma interferon, tumor necrosis factor alpha (TNF), and interleukin-10 (IL-10), in combination with IL-2, IL-5, or both. Two clones produced only Th1 cytokines, and none produced exclusively Th2 cytokines. Although IL-4 was not detected in cell culture supernatants, IL-4 mRNA was detected by polymerase chain reaction amplification in two of six clones. There were no differences between the cytokine profiles of alpha beta and gamma delta T cells. A striking finding was the markedly elevated concentrations of TNF in clone supernatants, independent of the other cytokines produced. Supernatants from mycobacterium-stimulated T-cell clones, in combination with granulocyte-macrophage colony-stimulating factor, induced aggregation of bone-marrow-derived macrophages, and this effect was abrogated by antibodies to TNF. The addition of recombinant TNF to granulocyte-macrophage colony-stimulating factor markedly enhanced macrophage aggregation, indicating that TNF produced by T cells may be an important costimulus for the granulomatous host response to mycobacteria. The cytokines produced by T cells may exert immunoregulatory and immunopathologic effects and thus mediate some of the clinical manifestations of tuberculosis.
 ...
PMID:Patterns of cytokine production by mycobacterium-reactive human T-cell clones. 841 42

The present review has summarized evidence supporting the existence of different lymphoid subsets with opposing effects on hematopoietic cell growth (Table 1); specifically; a) growth stimulation resulting from the release of interleukins and granulocyte-macrophage colony-stimulating factor (GM-CSF) by particular subsets of lymphocytes and resting natural killer (NK) cells and b) growth inhibition resulting from the release of interferon (IFN) and tumor necrosis factor (TNF) by stimulated NK, B and lymphokine-activated killer (LAK) cells and inhibitory T lymphoid subsets. The systematic examination of the physiologic relevance of lymphoid subsets would add an important element to a more comprehensive model of hematopoietic regulation that might hold promise in future clinical applications.
 ...
PMID:The role of lymphoid cells in hematopoietic regulation. 850 May 75

An adult T cell leukemia cell line, HIL-3, constitutively secretes a factor which induces the phenotypical and functional eosinophilic differentiation of a human eosinophilic leukemia cell line, EoL-1. Biochemical characteristics of the factor, termed eosinophilic leukemia cell differentiation factor (ELDF), were examined. ELDF was precipitated by 35 to 65% saturated ammonium sulfate from the culture supernatants of HIL-3 cells (HIL-3 sup). ELDF was eluted in a peak corresponding to a molecular weight of 30 to 40 kd by gel filtration. Isoelectric focusing in the Rotofor showed that ELDF had isoelectric points of 5 to 6. ELDF was trypsin-sensitive and stable to heat treatment at 65 degrees C for 30 minutes but labile at 80 degrees C or pH lower than 3. Half of the activity adhered to lentil-lectin but not to Con-A, indicating that a part of ELDF is glycoprotein with an N-linked carbohydrate moiety, which did not seem to be essential for ELDF activity. The biochemical characteristics of ELDF and blocking experiments using cytokine-specific neutralizing antibodies suggest that ELDF is different from gamma-interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-5 (IL-5) and interleukin-2 (IL-2), which may exist in HIL-3 sup, and that ELDF may be a previously unrecognized leukemia differentiation factor.
 ...
PMID:Characterization of an eosinophilic leukemia cell differentiation factor (ELDF) produced by a human T cell leukemia cell line, HIL-3. 850 May 76

Two patients with idiopathic hypereosinophilic syndrome (HES) refractory to treatment with corticosteroids and hydroxyurea received alpha-interferon (alpha-IFN) for 3 and 1 years, respectively. Eosinophil counts dropped below 1.5 x 10(9)/l at weekly doses of 2-7 x 3 million units alpha-IFN. More than a year after discontinuation of alpha-IFN, 1 patient remains in a stable remission. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plasma levels were found to be normal in this patient, although GM-CSF is known to stimulate eosinophil proliferation in vitro. Based on the favorable clinical results of alpha-IFN, further studies are necessary to define its role in the treatment of HES.
 ...
PMID:Sustained remission of idiopathic hypereosinophilic syndrome following alpha-interferon therapy. 850 51

Megakaryocytes and endothelial cells, two important blood and vascular cells, share many similar antigens on their surfaces and in the cytoplasm. It is known that the two types of cells share several developmental regulators: fibroblast growth factors, granulocyte-macrophage colony-stimulating factor, heparin and heparan sulfate, platelet factor 4, transforming growth factor-beta, gamma-interferon, and thrombospondin. Recognition of these common factors and studies with them are broadening the understanding of the pathogenesis of megakaryocytic and angiogenic diseases and encouraging attempts to develop new therapeutic strategies for the future.
 ...
PMID:Are megakaryocytes and endothelial cells sisters? 850 91


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