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)

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) was studied for its ability to stimulate the synthesis and release of the inflammatory mediator platelet-activating factor (PAF) from human neutrophils as measured by bioassay and incorporation of [3H]acetate into PAF. GM-CSF stimulated the synthesis but not the release of PAF from neutrophils. PAF synthesis took place in a time- and concentration-dependent manner, was dependent on a pertussis toxin-sensitive G protein and could be inhibited by antibodies to GM-CSF. On the other hand, pre-incubation of neutrophils with GM-CSF followed by stimulation with the bacterial tripeptide formylmethionylleucylphenylalanine caused PAF synthesis and release. The effect of GM-CSF was qualitative and not simply the result of larger amounts of PAF being synthesized since similar amounts were generated in response to the calcium ionophore A23187 but no released PAF could be detected. In functional studies GM-CSF stimulated superoxide anion generation from neutrophils with a time and dose relationship that paralleled PAF synthesis. In addition, the serine protease inhibitor L-1-tosylamide-2-phenylethyl chloromethyl ketone, which inhibits PAF synthesis, reduced PAF accumulation as well as superoxide generation, raising the possibility of a causal relationship between cell-associated PAF and cell activation. These results identify PAF as a direct product of GM-CSF stimulation in neutrophils where it may play a role in signal transduction and demonstrate that PAF is released only after subsequent neutrophil stimulation. The selective release of PAF may play a role in regulating and amplifying the inflammatory response.
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PMID:Granulocyte-macrophage colony-stimulating factor is a stimulant of platelet-activating factor and superoxide anion generation by human neutrophils. 184 28

Dendritic cells (DC) are potent antigen-presenting cells that govern the effector cell responses of the immune system. DC are thought to continuously develop from circulating progenitors in a process that is accelerated by inflammatory stimuli. However, the physiological signals that regulate the development of DC from precursor cells have not been well defined. Here we show that a serine protease acting via protease-activated receptor-2 (PAR-2) stimulates the development of DC from bone marrow progenitor cells cultured in granulocyte-macrophage colony-stimulating factor and IL-4. DC fail to develop in bone marrow cultures treated with soy bean trypsin inhibitor, a serine protease inhibitor, but this inhibition is overcome by a PAR-2 agonist peptide. DC do not spontaneously develop from the bone marrow of PAR-2-deficient mice, but can be stimulated to do so by inflammatory mediators. These results suggest that endogenous serine proteases stimulate DC development in vitro. Thus, serine proteases may help trigger adaptive immune responses in vivo.
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PMID:Protease-activated receptor-2 signaling triggers dendritic cell development. 1275 39

Dermal papilla cells (DPC) control the growth character of the hair follicle through their elaboration of mitogenic factors and extracellular matrix components. Further, the dermal papilla is a primary site of androgen action in the hair follicle. Interleukin-1alpha (IL-1alpha) is prominent in skin wounding and inflammatory responses although regarded as a negative hair growth regulator. We studied the effect of IL-1alpha and the potent androgen 5alpha-dihydrotestosterone (DHT) on the expression of the androgen receptor (AR) and various factors secreted by cultured human temporal scalp DPC. IL-1alpha triggered cellular changes consistent with nuclear factor-kappaB pathway activation as well as reduced AR mRNA and protein expression levels for DHT-stimulated DPC. This cytokine also increased DPC supernatant keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations. IL-1alpha did not influence DPC supernatant levels of transforming growth factor-beta1, a negative hair growth regulator. The stimulatory effect of IL-1alpha on DPC VEGF, GM-CSF, KGF, and IL-8 expression was also evident at the mRNA level for these cytokines. IL-1alpha also increased mRNA transcript levels of protease-nexin-1, a secreted serine protease inhibitor expressed in the dermal papilla of anagen-stage hair follicles. Although DHT did not affect supernatant cytokine concentrations, the androgen altered mRNA transcript levels of several factors for DPC co-stimulated with IL-1alpha. In consideration of its in vitro activity profile, IL-1alpha may be an important modifier of dermal papilla activity as well as potentially influence androgen-regulated gene expression in DPC.
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PMID:Influence of interleukin-1alpha on androgen receptor expression and cytokine secretion by cultured human dermal papilla cells. 1698 60

The market of therapeutic glycoproteins (including coagulation factors, antibodies, cytokines and hormones) is one of the profitable, fast-growing and challenging sectors of the biopharmaceutical industry. Although mammalian cell culture is still expensive and technically complex, the ability to produce desired post-translational modifications, in particular glycosylation, is a major issue. Glycans can influence ligand binding, serum half-life as well as biological activity or product immunogenicity. Aiming to establish a novel production platform for recombinant glycoproteins, the human TE671 cell line was investigated. Since the initial analysis of cell membrane proteins showed a promising glycosylation of TE671 cells for biotechnological purposes, we focused on the recombinant expression of two model glycoproteins of therapeutical relevance. The optimization of the cell transfection procedure and serum-free expression succeeded for the human serine protease inhibitor alpha-1-antitrypsin (A1AT) and the hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). N-glycan analyses of both purified proteins by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry provided first fundamental insights into the TE671 glycosylation potential. Besides protein specific pattern, strong distinctions - in particular for N-glycan fucosylation and sialylation - were observed depending on the medium conditions of the respective TE671 cell cultivations. The cell line's ability to synthesize complex and highly sialylated N-glycan structures has been shown. Our results demonstrate the TE671 cell line as a serious alternative to other existing human expression systems.
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PMID:The human rhabdomyosarcoma cell line TE671--Towards an innovative production platform for glycosylated biopharmaceuticals. 2627 70