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)

Blast cells derived from patients with acute myelogenous leukemia (AML) were cultured in the presence of interleukin-13 (IL-13). IL-13 did not cause statistically significant alterations of AML blast proliferation when cells were cultured in medium alone or together with IL-4, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. In contrast, IL-13 inhibited constitutive AML blast secretion of IL-1 alpha, IL-1 beta, IL-6, tumor necrosis factor alpha, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. IL-4 caused a similar inhibition of constitutive cytokine secretion as IL-13, but IL-13 caused no additive inhibition in the presence of IL-4. In contrast to IL-4 which increased AML blast release of IL-1 receptor antagonist, IL-13 caused no significant alteration of blast release of the receptor antagonist. IL-13 inhibited cytokine secretion also in the presence of neutralizing IL-4 and IL-10 antibodies and when AML blasts were cultures in serum-free conditions. We conclude that IL-13 has a direct and nontoxic inhibitory effect on constitutive AML blast cytokine secretion.
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PMID:Effects of interleukin-13 on cytokine secretion by human acute myelogenous leukemia blasts. 875 69

To challenge the concept of protective immunity in lymphatic filariasis, 19 adult residents of a Wuchereria bancrofti-endemic island who had been diagnosed 17 years earlier as putatively immune endemic normals (PI/EN) were reexamined. Even with continued exposure to infection, all 19 had maintained their apparent infection-free status. Studies to define the mechanisms underlying this putative immunity revealed that cellular immune responses (including proliferation; generation of interleukin [IL]-2, IL-5, IL-10, interferon-gamma, and granulocyte-macrophage colony-stimulating factor) to adult- and microfilarial-stage antigens, but not antibody responses, were markedly greater than those of 20 age-matched, infected patients. Furthermore, the PI/EN group was comprised of high- and low-responding persons who were clinically indistinguishable. These findings provide evidence that protective immunity to lymphatic filariasis does occur and that it is probably T cell-mediated.
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PMID:Evidence for protective immunity to bancroftian filariasis in the Cook Islands. 876 19

Sigma receptors originally described in distinct regions of the central nervous system are expressed on cells of the immune system. A sigma ligand, SR 31747A, was observed here to inhibit in vitro the Staphylococcal enterotoxin B (SEB)-driven lymphocyte proliferation. In mice, the drug confers a potent protection against the lethality induced by SEB, stimulates the SEB-induced serum release of interleukin (IL)-10 and inhibits at the same time the systemic release of IL-2, IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6 and tumour necrosis factor-alpha (TNF-alpha). The enhancement of IL-10 production by this compound is also effective in nude mice treated with SEB, indicating that IL-10 of T-cell origin is not involved in this process. The finding that a sigma ligand protects against the SEB-induced toxicity provides insights into the clinical use of this family of compounds, particularly in food poisoning and septic shock where Staphylococcal enterotoxins are involved. The observation that this compound stimulates IL-10 synthesis indicates that it could be a potent regulatory agent of chronic inflammatory diseases.
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PMID:A sigma ligand, SR 31747A, potently modulates Staphylococcal enterotoxin B-induced cytokine production in mice. 877 55

Human T-cell lymphotropic virus type I (HTLV-I) is known to cause adult T-cell leukemia/T-cell lymphoma and tropical spastic paraparesis/HTLV-I-associated myelopathy. Recent seroepidemiologic, clinical, and virologic studies indicate that the virus is also related to a certain type of uveitis, which has been classified as uveitis without defined etiologies or idiopathic uveitis. According to the seroepidemiologic survey, the seroprevalence of HTLV-I in patients with idiopathic uveitis was significantly higher than that of two control groups, that is, patients with uveitis with defined etiologies and patients with nonuveitic ocular diseases. Clinically, the uveitis seen in HTLV-I carriers is characterized by moderate to severe cellular infiltration in the eye and by moderate retinal vasculitis, and the intraocular inflammation responds well to corticosteroid therapy. Interestingly, 25% of female patients with the disease had a previous history of Graves disease with hyperthyroidisms. The following virologic, molecular biologic findings suggest that cytokines produced by HTLV-I-infected T cells in the eye play the central role in the pathogenic mechanisms of the uveitis: (a) the virus load in the peripheral blood monocytes analyzed by the quantitative polymerase chain reaction methods was significantly greater in patients with the uveitis than in asymptomatic carriers, (b) the proviral DNA of HTLV-I and the gene expression of the virus at the mRNA level was detected in the infiltrating cells from the eyes of the patients, (c) the virus particles were detected by electron-microscopic examination in the T-cell clones established from the intraocular fluid of the patients, and (d) the HTLV-I-infected T cells produced a variety of cytokines without any stimuli, such as interleukin (IL)-1 alpha, IL-2, IL-3, IL-6, IL-8, IL-10, tumor necrosis factor alpha, interferon-gamma, and granulocyte-macrophage colony-stimulating factor. Based on the seroepidemiologic, clinical, and virologic data, the uveitis seen in HTLV-I carriers is considered to be a distinct clinical entity related to HTLV-I infection, and the disease is designated as HTLV-I uveitis.
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PMID:HTLV-I uveitis. 879 4

Multinucleated giant cells (MGC) are a hallmark of granulomatous reactions but the mechanisms that regulate their formation are unknown. To address this issue, we cultured resident alveolar macrophages (AM) from rat lung and examined the effects of defined cytokines on AM differentiation and MGC formation. The presence of MGC was found after 3 days in culture with maximal numbers obtained at 7 days and thereafter (up to 21 days). Macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (25-75 U/mL) stimulated the formation of MGC (up to 4-fold), whereas interleukin (IL) -3, IL-10, and interferon-gamma (IFN-gamma) had no stimulatory effect. Interestingly, MGC with distinct phenotypes were observed in AM cultures: (1) spherical MGC with 3-16 nuclei, dense cytoplasm, and lower expression of beta3 integrin (Type 1) and (2) irregular MGC with 3-30 nuclei, thin and vacuolated cytoplasm, and higher expression of beta3 integrin (Type 2). Furthermore, the actions of M-CSF and GM-CSF on AM were found to be different. GM-CSF promoted, in AM cultures, the appearance of an elongated fibroblastoid phenotype and stimulated mostly the formation of Type 2 MGC. In contrast, M-CSF did not cause significant change in the general morphology of regular AM but stimulated the appearance of both Type 1 and Type 2 MGC. Reverse transcriptase-polymerase chain reaction analysis demonstrated that, under these conditions, M-CSF induced GM-CSF gene expression in AM. In addition, neutralizing antibodies against M-CSF selectively decreased the formation of Type 1 MGC, whereas neutralizing anti-GM-CSF inhibited Type 2 formation. These data suggest that M-CSF promotes AM differentiation into Type 1 MGC, whereas GM-CSF stimulates the formation of Type 2 and that M-CSF and GM-CSF may selectively regulate in an autocrine fashion AM differentiation into distinct MGC.
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PMID:M-CSF and GM-CSF promote alveolar macrophage differentiation into multinucleated giant cells with distinct phenotypes. 886 36

Nerve growth factor (NGF) promotes mast cell survival in vitro (Horigome, K., Bullock, E. D., and Johnson, E. M., Jr. (1994) J. Biol. Chem. 269, 2695-2702). NGF survival promotion is cell density-dependent, and conditioned medium experiments have shown that NGF increases the production of an autocrine mast cell survival activity. Cytokines are potential candidates for autocrine survival factors. In rat peritoneal mast cells (RPMC), NGF caused an increase in the messenger RNAs for interleukin (IL)-3, IL-4, IL-10, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor. This induction was NGF dose-dependent, was blocked by NGF-neutralizing antibodies, and was not observed in the non-mast peritoneal cell population. The immunosuppressive agent, cyclosporin A, blocked both cytokine induction and NGF-activated survival promotion but not survival promotion activated by IL-3 or stem cell factor, suggesting that NGF enhanced RPMC survival by increasing cytokine production. We also examine the effects of NGF on the expression levels of some members of the bcl-2 family and the interleukin-1beta-converting enzyme-like cysteine protease families. NGF markedly increased bcl-2 expression but had little or no effect on the other genes studied. The induction of bcl-2 mRNA by NGF was not blocked by cyclosporin A. These data suggest that induced cytokine gene expression but not increased expression of bcl-2 mediates NGF-survival promotion in RPMC.
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PMID:Nerve growth factor induces the expression of certain cytokine genes and bcl-2 in mast cells. Potential role in survival promotion. 891 Mar 34

Human CD38, a surface glycoprotein expressed by different immunocompetent cells, is associated with distinct transmembrane signaling molecules and plays a key role in the synthesis of cyclic ADP-ribose, a calcium-mobilizing compound. This study reports that CD38 ligation by specific monoclonal antibodies (mAb) in purified peripheral blood T cells is followed by secretion of discrete cytokines. IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-gamma, and IL-10 mRNA expression were constant findings. Low levels of IL-2 mRNA were also detected in CD38-activated T lymphocyte cultures of all subjects studied. Low levels of IL-4 and IL-5 mRNA were detected in the majority of CD38-activated T cultures. Moreover, CD38 mediated cytokine induction does not require T cell proliferation or the addition of antigen presenting cells. In conclusion, human CD38 runs an activation pathway in purified T cells which operates through the induction of a cytokine profile shared by Th1 or Th2 cells.
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PMID:Secretion of IFN-gamma, IL-6, granulocyte-macrophage colony-stimulating factor and IL-10 cytokines after activation of human purified T lymphocytes upon CD38 ligation. 891 76

Ehrlichia chaffeensis is a recently isolated minute gram-negative obligatory intracellular bacterium of monocytes/macrophages and is the etiologic agent of human monocytic ehrlichiosis. It is not known how macrophages respond when they encounter ehrlichiae in terms of cytokine production. In this study, we examined cytokine mRNA expression by incubating E. chaffeensis with THP-1 cells and performing competitive reverse transcription-PCR (RT-PCR). At 2 h postinfection, the levels of interleukin-1beta (IL-1beta), IL-8, and IL-10 mRNAs were significant but lower than those following Escherichia coli lipopolysaccharide (LPS) stimulation. Unlike the situation with E. coli LPS stimulation, however, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-alpha) mRNAs were not induced. Time course and dose-response studies confirmed the absence of IL-6, GM-CSF, and TNF-alpha mRNA induction with E. chaffeensis. Viable E. chaffeensis organisms were not required for IL-1beta IO, IL-8, and IL-10 mRNA induction, since heat-killed E. chaffeensis induced identical time course responses. IL-1beta, IL-8, and IL-10 mRNAs were detected for up to 21, 21, and 24 h postexposure with E. chaffeensis, respectively, which were shut off more rapidly than with LPS stimulation. Although heat treatment of E. chaffeensis had no effect, periodate treatment completely abolished the ability of E. chaffeensis to induce IL-1beta, IL-8, and IL-10 mRNAs. The capture enzyme-linked immunosorbent assay result corresponded with the RT-PCR results, showing that viable and heat-killed E. chaffeensis produced and secreted the same levels of IL-1beta and IL-8. IL-10 production was significantly reduced by heat treatment. Periodate-treated ehrlichiae did not induce production of any of the cytokines tested. Anti-CD14 monoclonal antibody and polymyxin B did not inhibit IL-1beta mRNA expression upon exposure to E. chaffeensis. The absence of TNF-alpha, IL-6, and GM-CSF mRNA induction may delay the development of a protective immune response, thereby allowing E. chaffeensis to set up residence in macrophages.
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PMID:Absence of tumor necrosis factor alpha, interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor expression but presence of IL-1beta, IL-8, and IL-10 expression in human monocytes exposed to viable or killed Ehrlichia chaffeensis. 892 90

The cytokine regulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF secretion by human umbilical cord vein endothelial cells (HUVEC) using quantitative immunoassays was studied. Unstimulated HUVEC produced no CSF. Interleukin 1 (IL-1), TNF and lipopolysaccharides (LPS) had stimulatory effects, with IL-1 being the most potent. GM-CSF and G-CSF secretion followed the same pattern, except that more GM-CSF was secreted. Exposure to stimuli for 30 min induced secretion, and detectable amounts in supernatants were found after 4 h incubation. CSF secretion was strictly regulated by the presence of a stimulus in a concentration dependent manner, and there were no signs of any endogenous downregulatory mechanism. No other cytokine tested had any stimulatory effect of its own. However, addition of IL-3 to stimulated HUVEC enhanced both GM-CSF and G-CSF secretion in a dose-dependent manner. In addition, TNF, and to a lesser degree LPS, enhanced IL-1-induced secretion. The only cytokine with a prominent downregulatory effect was IFN-gamma. IL-4 and IL-10, which downregulate CSF secretion by monocytes, had only minor effects.
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PMID:Cytokine regulation of GM-CSF and G-CSF secretion by human umbilical cord vein endothelial cells (HUVEC). 893 81

In a prospective study of 80 patients, we investigated the association of acute kidney graft rejection with pretransplant T helper/suppressor activity, B-cell responses, and in vitro cytokine secretion. Patients' CD4+ or CD8+ T cells were cocultured with control B cells and pokeweed mitogen for 6 days. SAC I was used for T cell- and monocyte-independent B-cell stimulation and pokeweed mitogen was used for T cell-dependent B-cell stimulation. B-cell differentiation was assessed in a reverse hemolytic plaque assay. Cytokine responses of T cells (interleukin [IL]-2, IL-10, gamma-interferon) and B cells/monocytes (IL-6, IL-8, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor) were determined in culture supernatants using ELISA. Subsets of CD4+ T cells, CD8+ T cells, and B cells were assessed by flow cytometry. None of 12 patients with pretransplant CD4 helper defects (CD4 helper activity < 10%) had acute rejection episodes, in contrast to 32 of 68 (47%) patients with normal pretransplant CD4 helper function (P = 0.001). Patients with pretransplant CD4 helper defects also had better 1-year graft function than patients without CD4 helper defects (serum creatinine 1.2 +/- 0.1 mg/dl and 1.7 +/- 0.1 mg/dl, respectively, P < 0.05). Pretransplant IL-10 responses were significantly associated with the occurrence of acute rejection episodes (P = 0.001) and impaired 1-year graft function (P < 0.001). All 14 patients with low pretransplant IL-10 responses (< 100 pg/ml) had 1-year serum creatinine values of < 1.5 mg/dl. Pretransplant B-cell defects and B cell/monocyte-derived cytokine secretion were not related to the incidence of graft rejection or infectious complications. Pretransplant CD8 suppressor-effector (CD11b+), cell counts were significantly associated with the occurrence of infections (P < 0.05). These results show that pretransplant CD4 helper defects and low IL-10 responses predict a low risk of graft rejection, whereas Th1 (IL-2, gamma-interferon) and B-cell/monocyte responses are not of predictive value.
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PMID:Pretransplant CD4 helper function and interleukin 10 response predict risk of acute kidney graft rejection. 897 Jun 16


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