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)

In order to test the hypothesis that ozone (O3)-induced changes in lung function and respiratory tract injury/inflammation are greater in subjects with asthma than in normal subjects, we exposed 18 asthmatic subjects, on separate days, to O3 (0.2 ppm) and filtered air for 4 h during exercise. Symptom questionnaires were administered before and after exposure, and pulmonary function tests (FEV1, FVC, and specific airway resistance [SRaw]) were performed before, during, and immediately after each exposure. Fiberoptic bronchoscopy, with proximal airway lavage (PAL) of the isolated left main bronchus and bronchoalveolar lavage (BAL; bronchial fraction, the first 10 ml of fluid recovered) of the right middle lobe, was performed 18 h after each exposure. The PAL, bronchial fraction, and BAL fluids were analyzed for the following endpoints: total and differential cell counts; total protein, lactate dehydrogenase (LDH), fibronectin, interleukin-8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF), myeloperoxidase (MPO), and transforming growth factor-beta (TGF beta 2) concentrations. We found a significant O3 effect on FEV1, FVC, SRaw (p < 0.04) and lower respiratory symptoms (p < 0.001) for the asthmatic subjects. Ozone exposure also significantly increased the percent neutrophils in PAL (p < 0.01); percent neutrophils, total protein, and IL-8 in the bronchial fraction (p < 0.001, p < 0.05, and p < 0.01, respectively); and the percent neutrophils, total protein, LDH, fibronectin, IL-8, GM-CSF, and MPO in BAL (p < 0.001, p < 0.01, p < 0.01, p < 0.001, p < 0.05, p < 0.01, and p < 0.001, respectively) for the asthmatic subjects. There were no significant differences in the lung function responses of the asthmatic subjects in comparison with a group of normal subjects (n = 81) previously studied using an identical protocol, although there was a trend toward a greater O3-induced increase in SRaw in the asthmatic subjects (p < 0.13). In contrast, the asthmatic subjects showed significantly greater (p < 0.05) O3-induced increases in several inflammatory endpoints (percent neutrophils and total protein concentration) in BAL as compared with normal subjects who underwent bronchoscopy (n = 20). Our results indicate that asthmatic persons may be at risk of developing more severe O3-induced respiratory tract injury/inflammation than normal persons, and may help explain the increased asthma morbidity associated with O3 pollution episodes observed in epidemiologic studies.
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PMID:Greater ozone-induced inflammatory responses in subjects with asthma. 868 Jun 87

Freshly excised human head and neck cancers (219 primary cancers; 64 metastatic lymph node cancers) were analyzed for the immune inhibitory mediators released from the cancer tissues and the immune infiltrate within the tumor. Significant levels of the immune inhibitory mediators transforming growth factor-beta (TGF-beta), prostaglandin E2 (PGE2) and interleukin-10 (IL-10) were released from these cancers. Also released was granulocyte-macrophage colony-stimulating factor (GM-CSF), whose secretion was associated with an intratumoral presence of CD34+ cells. We have previously shown that CD34+ cells within human head and neck cancers are immune inhibitory granulocyte-macrophage progenitor cells. The presence of TGF-beta, PGE2 and IL-10 was associated with a reduced content of CD8+ T-cells within the cancers. The CD4+ cell content appeared to be less affected by these immune inhibitory mediators. Instead, parameters indicative of CD4+ cell function (p55 IL-2 receptor expression, release of IL-2 and IFN-gamma) were diminished in cancers that released higher levels of TGF-beta, IL-10 and GM-CSF and had a higher CD34+ cell content. Furthermore, metastatic cancers released higher levels of the soluble immune inhibitory mediators and lower levels of IFN-gamma and IL-2 than did primary cancers, although CD34+ cells were similarly present in both primary and metastatic cancers. Our results show that human head and neck cancers have a multiplicity of non-mutually exclusive mechanisms of immune suppression that are most prominently associated with reduced CD8+ cell influx and reduced influx and altered function of intratumoral CD4+ cells.
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PMID:Mechanisms of immune suppression in patients with head and neck cancer: influence on the immune infiltrate of the cancer. 870 5

Macrophage colony-stimulating factor (M-CSF) is essential for murine osteoclast formation and its role in human hematopoiesis in vitro is not fully defined. Therefore, we have investigated the effect of M-CSF on the formation of human osteoclasts in vitro. M-CSF was found to induce substantial bone resorption and osteoclast formation in a dose-responsive and time-dependent manner above that induced by 1,25 dihydroxyvitamin D3 (1,25 vitamin D3) in cultures of human bone marrow (BM) stromal cells sedimented onto devitalized bone. By day 14 there was a mean of approximately 50% of the surfaces of the bone slices resorbed compared with only 6% in cultures treated with 1,25 vitamin D3 alone. Osteoclasts were identified as 23c6+ cells (an antibody that recognizes the vitronectin receptor), 87.5% of which coexpressed the calcitonin receptor. The number of 23c6+ cells correlated strongly with bone resorption spatially, and in a dose-responsive and time-dependent manner; the correlation coefficient in cultures treated with 1,25 vitamin D3 alone was 0.856 and those treated with both M-CSF and 1,25 vitamin D3 was 0.880. Granulocyte-macrophage colony-stimulating factor, IL-1 beta, IL-3, IL-6, tumor necrosis factor-alpha, transforming growth factor-beta, leukemia inhibitory factor, and IL-11 did not increase bone resorption above that in 1,25 vitamin D3-treated cultures. We also found that 1,25 vitamin D3 increased, to a minor but significant degree, both bone resorption and the concentration of M-CSF in the culture supernatants above that in vehicle-treated cultures, indicating that M-CSF is present in our BM cultures, but that there is insufficient to induce substantial osteoclast formation. These results define a critical role for M-CSF in the formation of human osteoclasts.
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PMID:Macrophage colony-stimulating factor induces substantial osteoclast generation and bone resorption in human bone marrow cultures. 883 45

Previous work has shown that enzymatic digestion of human placental tissue can induce the production of the cytokine interleukin-1 beta. Most studies of the feto-maternal interface of human pregnancy have used decidual cells prepared in a similar way, but the effects of tissue dissociation on the production of growth factors, cytokines, prostaglandins or hormones have not been investigated. Our studies show human decidual explants produce substantially lower levels of a range of factors than do human decidual cells cultured under the same conditions, indicating that induction may be a general process during the dissociation of tissues in vitro as the production of interleukins-1 beta, -6 and -8, granulocyte-macrophage colony-stimulating factor, transforming growth factor-beta 2, tissue necrosis factor-alpha, prostaglandins E2 and F2 alpha, and prolactin were all affected. The induction of cytokine production (expressed per mg tissue protein) ranged from 10- to 300-fold, indicating that isolated cells cultured in vitro may not reflect accurately the in vivo situation.
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PMID:A comparison of cytokine and hormone production by decidual cells and tissue explants. 895 92

We previously showed that interleukin-3 (IL-3) alone is not sufficient, although it is essential for murine mucosal-type mast cell development and that prostaglandin E (PGE) and interferon-gamma (IFN-gamma) are critical for survival or differentiation of mast cell precursors. We also confirmed that IL-4 is a key inhibitor for mast cell precursors despite being a growth factor of mast cells. In the present work, mouse spleen cells were cultured with recombinant (r) IL-1 beta, rIL-5, rIL-6, rIL-9, granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), tumor transforming growth factor-beta (TGF-beta), or tumor necrosis factor-alpha (TNF-alpha) in the presence of endogenous IL-3. After 12 days of culture, mast cell development was induced by rIL-6 and rTNF-alpha, rIL-1 beta, rIL-5, rGM-CSF, rTGF-beta and even the mast cell growth factors, rIL-9 and rSCF, failed to induce mast cell development. However, unlike IL-9 and SCF, IL-6 and TNF-alpha did not promote the growth of mast cells already developed. Macrophage may be one of the responsive cells of IL-6 and TNF-alpha in the cultures, because removal of macrophages greatly reduced the mast cell development induced by the cytokines. The actions of TNF-alpha and IL-6 were inhibited by indomethacin, an inhibitor for prostaglandin synthesis, and by neutralizing anti-IFN-gamma and anti-IL-3 antibodies. rIL-4, when added at the start of the culture, also inhibited mast cell development induced by rIL-6 and rTNF-alpha. Nevertheless, neutralizing anti-IL-6 and anti-TNF-alpha antibodies did not suppress mast cell development induced by PGE and IFN-gamma. TNF-alpha and IL-6 enhanced IFN-gamma production, but suppressed IL-4 production in the cultures. Mast cell numbers induced were inversely and directly proportional to IL-4 and IFN-gamma levels, respectively. These results indicate that inflammatory mediators as triggers are important for mast cell development although they are not the mast cell growth factors.
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PMID:Tumor necrosis factor-alpha- and interleukin-6-triggered mast cell development from mouse spleen cells. 900 55

The unstimulated and induced production of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), IL-3, IL-6, stem cell factor (SCF), IL-1beta, tumour necrosis factor-alpha (TNF-alpha), TNF-beta, interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) was determined after culture of blood mononuclear cells from 22 patients with severe beta-thalassaemia in a regular transfusion programme, five non-regularly transfused patients with beta-thalassaemia intermedia and nine normal persons. A distinct pattern of cytokine production in thalassaemic patients was detected, namely a low unstimulated production of all cytokines and a significant increase in the stimulated production of IFN-gamma, TNF-alpha and IL- 1beta; these abnormalities were more pronounced in the more heavily transfused older patients. The increased production of the above cytokines, which usually characterize the acute response to infectious agents and have a negative effect on erythropoiesis, may explain the deterioration of anaemia found in thalassaemic patients during acute infections.
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PMID:A distinct pattern of cytokine production from blood mononuclear cells in multitransfused patients with beta-thalassaemia. 906 38

Interleukin 1-beta (IL-1 beta), IL-2, IL-4, IL-5, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression was determined in knee synovium of 16 patients with rheumatoid arthritis (RA) and 16 patients with seronegative spondyloarthropathies (SSP), by using polymerase chain reaction (PCR) amplification. The pattern of cytokines observed in RA synovium is of the macrophage-fibroblast type, with the highest expression of IL-1 beta and TGF-beta. GM-CSF and IL-2 bands were visualized in a minority of patients. Neither IL-4 nor IL-5 could be detected. No significant differences were observed in the cytokine profile between patients with early (< 12 months) and more advanced disease. No differences were observed according to gender, age, rheumatoid factor status and the duration of knee synovitis. The pattern of cytokines in the synovium of SSP patients is similar to that observed in RA patients and does not change in relation to disease duration. IL-2 was the only T-cell cytokine observed. These data provide evidence that the macrophage-fibroblast cells have an important role in early and more advanced rheumatoid synovitis, and show that this is also true for SSP peripheral synovitis.
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PMID:Comparative cytokine gene expression in synovial tissue of early rheumatoid arthritis and seronegative spondyloarthropathies. 911 72

CD34+ cord blood (CB) cells were expanded in stromal cell-free long-term culture (LTC), in the presence of various combinations of interleukin-3 (IL-3), stem cell factor (SCF), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and anti-transforming growth factor-beta (anti-TGF-beta) antibody. The progenitor cell expansion was evaluated by monitoring the increase of CD34+ and CD34 + CD38- cells over a period of 21 days. The expansion of immature (B1-CFC, HPP-CFC) and of more committed progenitors (CFU-GM, CFU-GEMM, BFU-E) was also evaluated in specific samples. Our results show that (a) CD34+ cell expansion is highly variable depending on the cord blood samples studied, (b) significant correlations between B1-CFC and CD34 + CD38- and between total CFU and CD34+ cell expansion are observed, (c) SCF in combination with IL-3 appears to expand cell subsets that continue to express their CD34 + CD38- phenotype and that generate both immature and committed progenitors, and (d) the addition of IL-6, GM-CSF, or anti-TGF-beta does not significantly improve these expansions.
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PMID:Ex vivo expansion of CD34 + CD38- cord blood cells. 913 38

Receptor-type serine/threonine kinases (RSKs) have been organized into two distinct classes known as types I and II on the basis of sequence similarity. However, experiments have shown ligand specificities in the two classes and as a result type I and type II receptors can often bind to a common ligand. The transforming growth factor-beta- (TGF-beta) specific receptors represent such a case, where both type I and II receptors (T beta RI and T beta RII) are observed. Of additional interest is the observation that heteromeric associations of type I and II receptors can also enable signaling. To further elucidate the function of various RSKs, the extracellular domains of both alpha and beta chains from human granulocyte-macrophage colony-stimulating factor receptors were linked to transmembrane cytoplasmic domains of RSKs. Chimeric receptors of human granulocyte-macrophage receptor (hGMR) alpha with T beta RI and hGMR beta with T beta RII were expressed in murine pre-B cell-derived Ba/F3 cells. These chimeras formed heteromeric complexes, transmitted TGF-beta signals, and were down-modulated in response to human granulocyte-macrophage colony-stimulating factor. However, experiments utilizing these chimeric receptors in different combinations revealed that only heteromeric associations of transmembrane cytoplasmic domains mediated signaling and down-modulation. Chimeric receptors with transmembrane cytoplasmic domains of activin receptor type II and bone morphogenetic protein receptor type II also provided signals in conjunction with chimeric T beta RI. As a result, these type II receptors may share a common potential to signal via T beta RI. hGMR-RSK chimeric receptors may be useful tools for the identification and characterization of the divergent signals mediated by individual RSKs.
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PMID:A chimeric serine/threonine kinase receptor system reveals the potential of multiple type II receptors to cooperate with transforming growth factor-beta type I receptor. 918 99

Use of marijuana and cocaine is on the rise in the United States. Although pulmonary toxicity from these drugs has occasionally been reported, little is known about their effects on the lung microenvironment. We evaluated the function of alveolar macrophages (AMs) recovered from the lungs of nonsmokers and habitual smokers of either tobacco, marijuana, or crack cocaine. AMs recovered from marijuana smokers were deficient in their ability to phagocytose Staphylococcus aureus (p < 0.01). AMs from marijuana smokers and from cocaine users were also severely limited in their ability to kill both bacteria and tumor cells (p < 0.01). Studies using NG-monomethyl-L-arginine monoacetate, an inhibitor of nitric oxide synthase, suggest that AMs from nonsmokers and tobacco smokers were able to use nitric oxide as an antibacterial effector molecule, while AMs from smokers of marijuana and cocaine were not. Finally, AMs from marijuana smokers, but not from smokers of tobacco or cocaine, produced less than normal amounts of tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, and interleukin-6 when stimulated in culture with lipopolysaccharide. In contrast, the production of transforming growth factor-beta, an immunosuppressive cytokine, was similar in all groups. These findings indicate that habitual exposure of the lung to either marijuana or cocaine impairs the function and/or cytokine production of AMs. The ultimate outcome of these effects may be an enhanced susceptibility to infectious disease, cancer, and AIDS.
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PMID:Marijuana and cocaine impair alveolar macrophage function and cytokine production. 937 83


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