UNIPROT:P04141 - FACTA Search

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)

We investigated, in five cell strains per experiment, whether several cytokines known or believed to have effects on bone resorption were produced by nearly homogeneous strains of cultured normal human osteoblast-like (hOB) cells that display virtually the complete phenotype of the mature osteoblast. In unstimulated hOB cells, we detected constitutive production of interleukin-6 (IL-6) (mean +/- SE, 122 +/- 32 pg/ml) and IL-8 (135 +/- 39 pg/ml), but not of IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), or tumor necrosis factor-alpha (TNF alpha). IL-1 beta in doses from 1-100 U/ml stimulated dose-dependent increases in IL-6 (r = 0.87; P less than 0.001) and IL-8 (r = 0.95; P less than 0.001). Similar increases occurred after stimulation with TNF alpha in doses from 3-300 U/ml. IL-1 beta and TNF alpha also stimulated GM-CSF production, but only at higher doses. 17 beta-Estradiol (10(-8) M) had no significant effect on the secretion of any of these cytokines, either constitutively or after stimulation with IL-1 beta or TNF alpha. Stimulated production of IL-4 was not detected after treatment with IL-1 beta or TNF alpha, and that of TNF alpha was not detected after treatment with IL-1 beta. We conclude that IL-6, IL-8, and GM-CSF, but not IL-4 and TNF alpha, are produced by highly differentiated normal human cells of the osteoblast lineage, but their secretion is not regulated by estrogen. However, we cannot exclude the possibility that estrogen regulation of these cytokines may occur during early stages of osteoblast differentiation.
...
PMID:Production of various cytokines by normal human osteoblast-like cells in response to interleukin-1 beta and tumor necrosis factor-alpha: lack of regulation by 17 beta-estradiol. 157 80

In the present study, we show by Northern blot analysis and enzyme linked immunosorbent assay that the Hodgkin's disease (HD)-derived cell lines HDLM-2 and KM-H2 express a variety of cytokine genes either constitutively or upon induction with phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Cytokine genes expressed by HD-derived lines include granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, interleukin (IL)-1-alpha, IL-3, IL-5, IL-6, IL-8, leukemia inhibitory factor, tumor necrosis factor-alpha, tumor necrosis factor-beta, and transforming growth factor-beta, while transcripts and the corresponding proteins for granulocyte-CSF, IL-1-beta, IL-2, IL-4, IL-7, IL-10, and the JE/macrophage chemoattractant and activating factor gene were not detectable in cytoplasmic RNA and culture supernatants obtained from both lines. In addition, IL-2 receptor (R) p55 and macrophage-CSF R (c-fms) genes were expressed by both lines. HDLM-2, but not KM-H2 cells, exhibited the IL-6 R p80 and the IL-2 R p75 chain. Analysis of nuclear proteins that bind to oligonucleotides containing the consensus sequences of the transcription factors activation protein 1, nuclear factor (NF) kappa B, and NFAT 1 revealed a pattern for HD lines resembling that of activated T-cells: HDLM-2 and KM-H2 cells constitutively expressed NF binding to the NF of activated T-cells (type 1), previously described to be T-cell specific. In addition, NF kappa B-binding proteins obtained from both lines showed, in electrophoretic mobility shift assays, the same migration pattern as T-cell-derived proteins but differed from monocyte- and B-cell-derived proteins. UV cross-linking experiments confirmed that NF kappa B-binding proteins of M(r) 85,000, 75,000, and 50,000/55,000 were detectable in nuclear extracts obtained from T-cells and both HD lines, while monocytes and B-cells displayed the M(r) 50,000/55,000 and 75,000 NF kappa B complex only. Both HD lines also constitutively expressed transcripts for c-fos and c-jun, which are involved in heterodimeric formation of the transcription factor activation protein 1, as well as for the NF kappa B/KBF1 gene.
...
PMID:Expression of cytokine genes, cytokine receptor genes, and transcription factors in cultured Hodgkin and Reed-Sternberg cells. 159 93

Skin blisters induced by suction on the forearm of normal volunteers provide a convenient model to study the inflammatory response in vivo in man. In our study, after removal of the roof of the blister, i.e., the epidermis, the exposed floor of the blister (dermal-epidermal interface) was bathed with 70% autologous serum using a multiwell skin chamber. Migration of leukocytes (90-95% neutrophils) into the chamber fluid was detectable within 3 h, and appeared to plateau at 16-24 h. Sampling of the dermal-epidermal interface revealed primarily mononuclear cells during the first 8 h of the inflammatory response; however, their prevalence at 24 h was greatly diminished due to neutrophil infiltration. Accompanying the cellular immune response was the accumulation of inflammatory mediators in the bathing medium. The accumulation of IFN-gamma reached a plateau within 3 h; significant accumulations of the complement fragment, C5a, and of leukotriene B4 were also detected at 3 h. The accumulation of C5a did not peak until 5 h, whereas leukotriene B4 continued to accumulate through 24 h. IL-6 and IL-8 concentrations were minimal at 3-8 h but dramatic by 24 h while IL-1 beta, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor were undetectable within 3-8 h, but markedly elevated by 24 h. There was little accumulation of IL-4 and no accumulation of IL-1 alpha or IL-2 during the 24-h period. The sequential appearance of mediators at an inflammatory focus suggests that a carefully regulated dynamic system is responsible for controlling the evolution of the inflammatory response.
...
PMID:Dynamics of the cellular and humoral components of the inflammatory response elicited in skin blisters in humans. 160 84

Eosinophilia and eosinophil function are regulated by cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5. We have investigated the modulatory role of GM-CSF and IL-3 on the platelet-activating factor (PAF)-, neutrophil-activating factor (NAF/IL-8)-, leukotriene B4 (LTB4)-, N-formyl-methionyl-leucyl-phenylalanine (FMLP)-, and human complement factor C5a-induced chemotaxis of eosinophils from normal individuals. These eosinophils show a chemotactic response toward PAF, LTB4, and C5a, but not to NAF/IL-8 and FMLP. Preincubation of the eosinophils with picomolar concentrations of GM-CSF caused a significant increase in the response toward LTB4 and induced a significant chemotactic response toward NAF/IL-8 and FMLP. Preincubation of the eosinophils with picomolar concentrations of IL-3 also induced a chemotactic response toward NAF/IL-8 and FMLP, and enhanced the PAF-induced chemotaxis response toward C5a was not influenced by both cytokines. Nanomolar concentrations of GM-CSF or IL-3 caused a significant inhibition of the C5a-induced chemotaxis. The LTB4-induced chemotaxis was also significantly inhibited in case of GM-CSF. At these concentrations both GM-CSF and IL-3 acted as chemotaxins for eosinophils were washed after pretreatment with GM-CSF and IL-3 the potentiation of the chemotactic response remained, whereas the inhibitory mode of action disappeared. Our data indicate that at picomolar concentrations the cytokines GM-CSF and IL-3 can modulate eosinophil chemotaxis and at nanomolar concentrations these cytokines can act as chemotaxins for eosinophils.
...
PMID:Modulation and induction of eosinophil chemotaxis by granulocyte-macrophage colony-stimulating factor and interleukin-3. 164 45

Interleukin-8 (IL-8) stimulated an increase in cytoplasmic-free Ca2+ ([Ca2+]i) and intracellular pH (pHi) in parallel at low concentrations (0.5 to 5 ng/mL), and stimulated O2- release and membrane depolarization in parallel at high concentrations (50 to 5,000 ng/mL). IL-8-induced O2- release was potentiated by tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte-CSF (G-CSF) in a dose-dependent manner, whereas it was inhibited by cyclic AMP agonists. These characteristics and the time-courses of the responses stimulated by IL-8 were similar to those stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP), except that the cells stimulated by IL-8 showed shorter duration and less magnitude in some responses. In addition, IL-8 was found to be a potent priming agent and to enhance O2- release stimulated by FMLP. The priming effect of IL-8 was very rapid and was maximal within 5 minutes of preincubation. The dose-response curves for priming were identical to those for triggering of an increase in [Ca2+]i and pHi. The potency of the maximal priming effects on FMLP-induced O2- release was TNF greater than GM-CSF greater than IL-8 greater than G-CSF. The combination of IL-8 and the suboptimal concentrations of TNF or GM-CSF resulted in the additive priming effect, whereas the combination of the optimal concentration of IL-8 and the optimal concentration of TNF, GM-CSF, or G-CSF resulted in the effect of more potent priming agent alone. These findings suggest that IL-8 stimulates or primes human neutrophils according to its concentrations and cross-talks with TNF, GM-CSF, G-CSF, or FMLP at the inflammatory sites.
...
PMID:Stimulation and priming of human neutrophils by interleukin-8: cooperation with tumor necrosis factor and colony-stimulating factors. 172 9

A neutrophil chemotactic factor (human interleukin 8, human granulocyte-macrophage colony-stimulating factor)-producing cell line, named KHM-5M, was established from a patient with an undifferentiated thyroid carcinoma, neutrophilia, and malignant pleurisy with many neutrophils and a few malignant cells. The cell line was transplanted into nude rats, and the infiltration of neutrophils was observed in and around the transplanted tumor tissue. Neutrophil chemotactic activity was predicted from the clinical features and pathological findings in this case. The extreme chemotactic activity of the neutrophils was demonstrated in conditioned medium from KHM-5M cells using the modified Boyden chamber technique. With sodium dodecyl sulfate-polyacrylamide gel electrophoresis, at least two neutrophil chemotactic activities in conditioned medium from the cell line were observed. The levels of these activities derived from KHM-5M cells were screened by measuring conditioned medium from the COS cells, which expressed a complementary DNA library from the KHM-5M cells. Chemotactic activities (human interleukin 8, human granulocyte-macrophage colony-stimulating factor) were identified by DNA cloning. These results show that the KHM-5M cells derived from an undifferentiated thyroid carcinoma produce multicytokines and suggest that those cytokines modified some pathological features in this case.
...
PMID:Neutrophil chemotactic factors produced by a cell line from thyroid carcinoma. 172 17

We have studied cytokine expression by the human bladder carcinoma cell line 5637 using a cDNA-PCR procedure. Transcripts for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-7, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, M-CSF, tumor-necrosis factor-alpha (TNF-alpha), and TNF-beta were constitutively present, whereas IL-3, IL-4, IL-5, and IL-9 mRNA sequences could not be detected. This expression pattern was not altered after 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulation (4 and 8 h) of 5637 cells. Relative expression levels of cytokines were assessed by limiting dilution of the cDNA pool. This procedure proved to be a semiquantitative technique when compared to Northern blot analysis.
...
PMID:Cytokine production by the bladder carcinoma cell line 5637: rapid analysis of mRNA expression levels using a cDNA-PCR procedure. 188 17

In the present study we demonstrate that human monocytes activated by lipopolysaccharides (LPS) were able to produce high levels of interleukin 10 (IL-10), previously designated cytokine synthesis inhibitory factor (CSIF), in a dose dependent fashion. IL-10 was detectable 7 h after activation of the monocytes and maximal levels of IL-10 production were observed after 24-48 h. These kinetics indicated that the production of IL-10 by human monocytes was relatively late as compared to the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), and granulocyte colony-stimulating factor (G-CSF), which were all secreted at high levels 4-8 h after activation. The production of IL-10 by LPS activated monocytes was, similar to that of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF, inhibited by IL-4. Furthermore we demonstrate here that IL-10, added to monocytes, activated by interferon gamma (IFN-gamma), LPS, or combinations of LPS and IFN-gamma at the onset of the cultures, strongly inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF at the transcriptional level. Viral-IL-10, which has similar biological activities on human cells, also inhibited the production of TNF alpha and GM-CSF by monocytes following LPS activation. Activation of monocytes by LPS in the presence of neutralizing anti-IL-10 monoclonal antibodies resulted in the production of higher amounts of cytokines relative to LPS treatment alone, indicating that endogenously produced IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF. In addition, IL-10 had autoregulatory effects since it strongly inhibited IL-10 mRNA synthesis in LPS activated monocytes. Furthermore, endogenously produced IL-10 was found to be responsible for the reduction in class II major histocompatibility complex (MHC) expression following activation of monocytes with LPS. Taken together our results indicate that IL-10 has important regulatory effects on immunological and inflammatory responses because of its capacity to downregulate class II MHC expression and to inhibit the production of proinflammatory cytokines by monocytes.
...
PMID:Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. 194 Jul 99

Activated polymorphonuclear neutrophilic granulocytes (PMN) play an important role in propagation of inflammatory reactions and are capable of mediating tissue damage particularly by release of reactive oxygen species and lysosomal contents. Cytokines produced by monocytes as well as epidermal cells were recently shown to modulate PMN function. Therefore, the effect of immunomodulating cytokines on the oxidative metabolism of isolated human PMN was tested by functional as well as ultrastructural criteria. The following recombinant human cytokines were tested: tumor necrosis factor (TNF alpha), lymphotoxin (TNF beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, G-CSF, PDGF, TGF-beta, interleukin-1 (IL-1) alpha and beta, IL-2, IL-3, IL-4, IL-5, IL-6, MONAP/MOC/NAF (IL-8), interferon-alpha and -gamma. Only TNF alpha, TNF beta and GM-CSF were found to be direct stimuli of the oxidative burst in human PMN whereas IL-3, IL-5, and IL-8 were active only at extremely high concentrations. None of the other cytokines tested induced any significant effect on isolated human PMN at physiological concentrations. The results clearly demonstrate that only selected cytokines are capable of inducing a long lasting activation of PMN oxidative metabolism. Release of these mediators represents a specific signal for PMN activation in inflammatory disease states.
...
PMID:Activation of the oxidative metabolism in human polymorphonuclear neutrophilic granulocytes: the role of immuno-modulating cytokines. 225 41

Interleukin (IL)-3 stimulates hemopoiesis in vitro. However, IL-3 is not normally found in bone marrow, raising doubts as to the in vivo role of IL-3. We have found that human umbilical vein endothelial cells (HUVEC) express functional high-affinity receptors for IL-3 after stimulation with tumor necrosis factor alpha (TNF-alpha), IL-1 beta, or lipopolysaccharide, and that this receptor is involved in inflammatory phenomena. TNF-alpha caused time- and dose-dependent up-regulation of mRNA for the IL-3 receptor alpha and beta chains, with maximal effects occurring 16-36 h after stimulation with TNF-alpha at 100 units/ml. Induction of mRNA correlated with protein expression on the cell surface as judged by monoclonal antibody staining and by the ability of HUVEC to specifically bind 125I-labeled IL-3. Scatchard analysis under optimal conditions of TNF-alpha stimulation revealed approximately 1500 IL-3 receptors per cell, which were of a high-affinity class (Kd = 500 pM) only. In contrast to a previous report, receptors for granulocyte-macrophage colony-stimulating factor could not be detected. IL-3 binding to TNF-alpha-activated HUVEC enhanced IL-8 production, E-selection expression, and neutrophil transmigration. The selective induction of a functional IL-3 receptor on endothelial cells suggests that, beyond hemopoiesis, IL-3 may have an important role in chronic inflammation and in allergic diseases.
...
PMID:The receptor for interleukin 3 is selectively induced in human endothelial cells by tumor necrosis factor alpha and potentiates interleukin 8 secretion and neutrophil transmigration. 824 92

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