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)

The incidence of infections with Candida albicans and also with non-albicans yeast species is increasing rapidly, particularly in immunocompromised patients. Eight Candida and Torulopsis species were compared for their ability to stimulate production of complement components C3 and factor B by monocytes. In addition, the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) was determined, because this cytokine affects monocyte complement production. The highest ranked pathogenic yeasts, i.e., C. albicans, C. tropicalis and C. parapsilosis, were the most effective inducers of C3, factor B and GM-CSF production. C. krusei and T. glabrata showed intermediate activity, whereas C. kefyr, C. guilliermondii and T. candida had only a moderate stimulatory effect on C3 production and did not affect either factor B or GM-CSF release. The stimulated cytokine and complement production in response to the yeasts was highly variable in monocytes from different donors, but there was a consistent inverse relationship between C3 and GM-CSF concentrations in the monocyte supernates. This is in agreement with the previously described suppressive effect of GM-CSF on yeast-induced C3, but not factor B production. The monocyte responses elicited by a specific yeast species may be linked to its pathogenicity, and may also explain the predilection of some yeasts for particular underlying diseases.
 ...
PMID:Various Candida and Torulopsis species differ in their ability to induce the production of C3, factor B and granulocyte-macrophage colony-stimulating factor (GM-CSF) in human monocyte cultures. 770 38

Polymyxin B (PmB), an agent often used to neutralize the effects of bacterial lipopolysaccharide (LPS), was shown to exert a dose-dependent stimulatory effect on the biosynthesis of C3, factor B, interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in human monocytes. A low dose of PmB (1 to 5 micrograms/ml) efficiently suppressed the LPS-induced (1 or 100 ng/ml) production of IL-6, GM-CSF, and factor B, but not the C3 production induced by 100 ng of LPS per ml. A reduced level of GM-CSF may have contributed to the persisting high C3 concentrations and the apparent lack of LPS inhibition in the latter situation, since GM-CSF is an inhibitor of monocyte C3 biosynthesis.
 ...
PMID:Polymyxin B stimulates production of complement components and cytokines in human monocytes. 772 27

Complement biosynthesis in monocytes is stimulated by different pathogens and modulated by a variety of cytokines, but little is known about the possible effect of transforming growth factor beta (TGF-beta) on this monocyte function. We therefore studied the effect of TGF-beta 1 and TGF-beta 2 on constitutive, lipopolysaccharide (LPS)- and Candida albicans-induced monocyte biosynthesis of complement components C3 and factor B. Under all three conditions, both forms of TGF-beta (20 ng/ml) induced a two- to fourfold increase in C3 concentration in monocyte supernatants harvested after 2 or 5 days of cell culture, an effect that was abrogated by cycloheximide. In contrast, constitutive and pathogen-induced production of factor B was suppressed by TGF-beta. The effects of TGF-beta on complement production were neutralized by a monoclonal anti-TGF-beta antibody. Moreover, TGF-beta suppressed the pathogen-induced release of granulocyte-macrophage colony-stimulating factor and down-regulated the expression of complement receptor 3 (CD11b/CD18), while the expression of CD11a/CD18, a related beta 2 integrin, was unaffected. These novel effects of TGF-beta emphasize the immunomodulatory significance of this cytokine.
 ...
PMID:Transforming growth factor beta modulates C3 and factor B biosynthesis and complement receptor 3 expression in cultured human monocytes. 785 44

Activation of the complement system is an important part of host resistance against fungal infections. When human monocytes, cultured for 2 days or more, were treated in vitro with Candida albicans for 24 h, an enhancement of their biosynthesis of the complement components C3 and factor B was found. However, when C. albicans was administered to freshly isolated monocytes, a consistent stimulation of factor B biosynthesis occurred, while the C3 production was increased in about 50% of the donors. C. albicans also induced the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) from the cultured cells, apparently in larger amounts in the donors in whom no stimulation of C3 production was found. An antibody to GM-CSF administered with the yeast at the initiation of the monocyte culture caused an increase in the C3 production. Furthermore, when monocytes were treated with recombinant human GM-CSF either at the same time as or 4 days prior to the addition of C. albicans, the increase in C3 production was suppressed or neutralized, while factor B biosynthesis was unaffected. Taken together, these results indicate that monocytes respond to C. albicans with an increased production of complement factors. This may be an important mechanism both for opsonization of the fungus and for initiation of an inflammatory reaction. At an inflammatory site, this complement response may be suppressed by locally produced GM-CSF.
 ...
PMID:Increased C3 production in human monocytes after stimulation with Candida albicans is suppressed by granulocyte-macrophage colony-stimulating factor. 847 67