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

Previous work in our laboratory has shown that corticosterone increases the susceptibility of macrophages from Bcgs mice to the growth of Mycobacterium avium. The innate antimycobacterial activity of macrophages from Bcgr mice was not affected by corticosterone. In contrast to the differential effect of corticosterone on the antimycobacterial activity of the macrophages, corticosterone suppressed the production of tumor necrosis factor alpha and nitric oxide by macrophages from both Bcgr and Bcgs mice. The purpose of this investigation was to compare the effects of corticosterone on the antimycobacterial activity of macrophages from Bcgr and Bcgs mice that have been activated in vitro with recombinant gamma interferon or granulocyte-macrophage colony-stimulating factor. We found that macrophages from both strains of congenic mice responded equally to the activation stimuli. The capacity of the activated macrophages from Bcgs mice to suppress the growth of M. avium was inhibited by the addition of corticosterone to the cultures. The addition of NG-monomethyl-L-arginine to the cultures did not affect the capacity of resident splenic macrophages from Bcgr mice to limit the growth of M. avium. However, NG-monomethyl-L-arginine reduced the capacity of gamma interferon-activated, but not granulocyte-macrophage colony-stimulating factor-activated, macrophages to limit the growth of M. avium by macrophages from both Bcgr and Bcgs mice. The addition of corticosterone suppressed Nramp expression by macrophages from Bcgs mice. Nramp expression by macrophages from Bcgr mice was not affected by corticosterone.
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PMID:Cytokine-mediated activation of macrophages from Mycobacterium bovis BCG-resistant and -susceptible mice: differential effects of corticosterone on antimycobacterial activity and expression of the Bcg gene (Candidate Nramp). 762 20

The effects of ofloxacin, clarithromycin, and azithromycin in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) against Mycobacterium avium-Mycobacterium intracellulare (MAI) were evaluated in an in vitro human macrophage infection model. Treatment of MAI-infected macrophages with GM-CSF alone induced a maximal killing effect at 1000 U/mL, and the potency was increased 100-fold by encapsulating the cytokine within liposomes. Antibiotics were applied at concentrations close to their clinically achievable serum trough and peak levels. Addition of GM-CSF to azithromycin and therapeutic trough concentrations of ofloxacin and clarithromycin was associated with significant (P < .01) augmentation of antimycobacterial activity compared with the effects of the agents alone. However, the enhancement effect by GM-CSF was not seen with therapeutic peak concentrations of ofloxacin and clarithromycin. Thus, GM-CSF may be a useful adjunct in the treatment of MAI infections with azithromycin, clarithromycin, and ofloxacin.
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PMID:Activities of clarithromycin, azithromycin, and ofloxacin in combination with liposomal or unencapsulated granulocyte-macrophage colony-stimulating factor against intramacrophage Mycobacterium avium-Mycobacterium intracellulare. 765 75

Infection caused by organisms of the Mycobacterium avium complex is diagnosed in 50% to 60% of AIDS patients with the advanced stage of disease. Mycobacterium avium is an environmental bacterium that gains access to the host through both the gastrointestinal tract and the respiratory tract. After crossing the mucosal barrier Mycobacterium avium disseminates, infecting chiefly mononuclear phagocytes of the reticuloendothelial system. A number of cells of the immune system such as CD4+ T cells, natural killer cells and macrophages have been shown to be involved in the host response to Mycobacterium avium. The interaction between Mycobacterium avium and macrophages results in the production of immune-suppressive cytokines that inhibit the effector function of TH1 subtype CD4+ T cells, natural killer cells and macrophages, possibly allowing survival of Mycobacterium avium. Some cytokines such as tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor have been shown to induce mycobacteriostatic activity and mycobactericidal activity in infected macrophages. Over the next few years, much new information will certainly be gleaned about host-pathogen interactions, which will lead to a better understanding of the disease and possibly to the design of new forms of therapy.
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PMID:Immunobiology of Mycobacterium avium infection. 769 13

Knowing how mycobacteria exploit host cytokines to survive and which cytokines have important roles in host defense against mycobacteria should allow the use of these molecules in the treatment of mycobacterial infections. Both interleukin 2 and interferon gamma have been used to treat patients with leprosy, and granulocyte-macrophage colony-stimulating factor is presently being administered to AIDS patients infected with Mycobacterium avium.
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PMID:Recombinant cytokines for controlling mycobacterial infections. 771 35

Bacterial heat shock proteins (hsp) have been shown to be important immunogens stimulating both T cells and B cells. However, little is known concerning the direct interactions between hsp and macrophages. In this study, we demonstrated that treatment of macrophage cultures with purified bacterial hsp, including Legionella pneumophila hsp60, Escherichia coli GroEL, Mycobacterium tuberculosis hsp70, Mycobacterium leprae hsp65, and Mycobacterium bovis BCG hsp65, increased the steady-state levels of cytokine mRNA for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor as well as supernatant IL-1 secretion. This effect was shown not to be due to contamination of the hsp preparations with bacterial lipopolysaccharide. However, not all hsp induced cytokines; M. tuberculosis hsp10 showed minimal activity in our study. These results suggest that bacterial hsp might modulate immunity by rapidly and directly increasing cytokine production in macrophages.
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PMID:Bacterial heat shock proteins directly induce cytokine mRNA and interleukin-1 secretion in macrophage cultures. 796 Jan 55

Mycobacterium bovis BCG was genetically engineered to express and secrete mouse interleukin-2 (IL-2) and rat IL-2. Genes encoding IL-2 were inserted into an Escherichia coli-BCG shuttle plasmid under the control of the BCG HSP60 promoter. To facilitate study of proteins produced in this system, the IL-2 gene product was expressed (i) alone, (ii) with the mycobacterial alpha-antigen secretion signal sequence at the amino terminus, (iii) with an influenza virus hemagglutinin epitope tag at the amino terminus, and (iv) with both the secretion signal sequence and the epitope tag. When expressed with the alpha-antigen signal sequence, biologically active IL-2 was secreted into the extracellular medium. Western blot (immunoblot) analysis of the intracellular IL-2 and extracellular IL-2 revealed that the secretion signal was appropriately cleaved from the recombinant lymphokine upon secretion. To assess the ability of recombinant BCG to stimulate cytokine production in a splenocyte population, mouse splenocytes were cultured together with wild-type or IL-2-producing BCG. IL-2-secreting BCG clones stimulated substantial increases in gamma interferon production, which could be reproduced by the addition of exogenous IL-2 to BCG. Levels of IL-6, IL-10, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor were not significantly changed, while IL-4 and IL-5 remained undetectable (less than 50 pg/ml). The enhanced production of gamma interferon in response to IL-2-secreting BCG was strain independent. Recombinant BCG expressing mammalian cytokines provides a novel means to deliver cytokines and may augment the immunostimulatory properties of BCG in immunization and cancer therapy.
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PMID:Recombinant Mycobacterium bovis BCG secreting functional interleukin-2 enhances gamma interferon production by splenocytes. 818 76

Availability of mice with a targeted disruption of the interferon gamma (IFN-gamma) receptor gene (IFN-gamma R0/0 mice) made it possible to examine parameters of macrophage activation in the absence of a functional IFN-gamma receptor. We asked to what extent other cytokines could replace IFN-gamma in the induction of nitric oxide or major histocompatibility complex class II antigen (Ia) expression in peritoneal macrophages. In thioglycollate-elicited macrophages from wild-type mice, tumor necrosis factor (TNF) alone was virtually ineffective in inducing release of NO2- (the endproduct of nitric oxide generation), but TNF enhanced NO2- release in the presence of IFN-gamma. In macrophages from IFN-gamma R0/0 mice, which were unresponsive to IFN-gamma, TNF completely failed to stimulate NO2- release. The stimulatory actions of IFN-alpha/beta on NO2- release were indistinguishable in wild-type and IFN-gamma R0/0 macrophages: IFN-alpha/beta was ineffective on its own, showed marginal stimulation of NO2- release in combination with TNF, and was moderately effective in the presence of lipopolysaccharide. The level of constitutive Ia antigen expression was not significantly different in peritoneal macrophages from wild-type and IFN-gamma R0/0 mice. An increased Ia expression was induced by IL-4 and granulocyte-macrophage colony-stimulating factor in both wild-type and IFN-gamma R0/0 macrophages, but the magnitude of this induction was less than with optimal concentrations of IFN-gamma in macrophages from wild-type mice. IFN-alpha/beta showed only a minor stimulatory effect on Ia expression in both wild-type and IFN-gamma R0/0 macrophages. Simultaneous treatment of wild-type macrophages with IFN-alpha/beta and IFN-gamma reduced the IFN-gamma-induced Ia expression in wild-type macrophages, but IFN-alpha/beta did not show an inhibitory effect on IL-4- or granulocyte-macrophage-colony-stimulating factor-induced Ia expression in either wild-type or IFN-gamma R0/0 macrophages. The important role of IFN-gamma in the regulation of the induced expression of major histocompatibility complex class II antigen was confirmed by showing that after systemic infection with the BCG strain of Mycobacterium bovis resident peritoneal macrophages from IFN-gamma R0/0 mice had a lower level of Ia expression than macrophages from wild-type mice. The inability of other cytokines to substitute fully for IFN-gamma in macrophage activation helps to explain the earlier observed decreased resistance of IFN-gamma R0/0 mice to some infections.
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PMID:Generation of nitric oxide and induction of major histocompatibility complex class II antigen in macrophages from mice lacking the interferon gamma receptor. 834 79

Murine intraepithelial lymphocytes (IEL) respond poorly to T cell mitogens and to monoclonal antibody stimulation of T cell receptor (TCR)- and CD3- associated molecules. In contrast, we found that a soluble extract of Mycobacterium tuberculosis (Mtb), but not purified protein derivative of tuberculin, induced significant proliferative responses in IEL cultures. The active component was apparently a heat shock protein (HSP), since recombinant 71-kDa HSP from Mtb induced IEL to proliferate, while 65-kDa HSP from M. bovis and M. leprae did not. Both alpha/beta and gamma/delta TCR-enriched IEL gave proliferative responses to 71-kDa HSP. Further, culture supernatants from IEL stimulated with 71-kDa HSP contained elevated levels of interleukin-(IL)-3/granulocyte-macrophage colony-stimulating factor, interferon-gamma and IL-6, but not IL-2, IL-4, IL-5 or transforming growth factor-beta. Finally, several IEL T cell clones have been maintained for up to 6 weeks, when stimulated with 71-kDa HSP, IL-2 and feeder cells. Our results show that the 71-kDa HSP of Mtb induces IEL T cells to divide and to secrete cytokines and this may offer a model for cloning and study of IEL T cells in vitro.
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PMID:The Mycobacterium tuberculosis 71-kDa heat-shock protein induces proliferation and cytokine secretion by murine gut intraepithelial lymphocytes. 834 73

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.
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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.
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PMID:Patterns of cytokine production by mycobacterium-reactive human T-cell clones. 841 42


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