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 determined the effect of inhaled corticosteroid, budesonide, on the release of the anti-inflammatory cytokine, interleukin-10 (IL-10), and of pro-inflammatory cytokines, macrophage inflammatory protein-1alpha (MIP-1alpha), interferon-gamma (IFN-gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF), from blood monocytes and alveolar macrophages of mild asthmatic subjects in a double-blind, cross-over, placebo-controlled study. Budesonide reduced bronchial hyperresponsiveness and improved baseline FEV1. Alveolar macrophages were obtained by bronchoalveolar lavage performed at the end of each treatment phase. IL-10 from blood monocytes was not altered, but both IL-10 mRNA and protein expression from alveolar macrophages stimulated by lipopolysaccharide and IL-1beta were increased after corticosteroid therapy. By contrast, alveolar macrophages released significantly less MIP-1alpha, IFN-gamma, and GM-CSF after steroid treatment. In comparison to alveolar macrophages from normal nonasthmatic volunteers, those from asthmatic patients released more MIP-1alpha, IFN-gamma, and GM-CSF but lower amounts of IL-10 particularly at baseline and after IL-1beta stimulation. The ability of steroids to inhibit pro-inflammatory cytokines but to enhance the anti-inflammatory cytokine such as IL-10 may contribute to their beneficial actions in asthma. Asthma is characterized by alveolar macrophages exhibiting both an enhanced capacity to release pro-inflammatory cytokines and a reduced capacity to produce IL-10.
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PMID:Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1alpha, granulocyte-macrophage colony-stimulating factor, and interferon-gamma release from alveolar macrophages in asthma. 944 7

Interleukin 12 (IL-12) has a key role during the initial phase of the immune response, favouring development of T helper class 1 (Th1) cells. IL-12 is composed of two subunits, p35 and p40, which are both needed for bioactivity. The level of p35 expression determines the level of bioactive IL-12 (p70), while the p40 subunit is produced in excess. In the present study we examined the sensitivity of bioactive IL-12 production by human monocytes to a corticosteroid, budesonide. We also compared the corticosteroid sensitivity of IL-12 and two other cytokines, interleukin 1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocytes obtained from peripheral blood of healthy donors (n=12) were stimulated with lipopolysaccharide (LPS; 10 microg/ml; 20 h) in the presence or absence of budesonide (10(-11)-10(-7) M). The supernatants were assayed for IL-12 (p70), IL-1beta and GM-CSF concentrations using specific immunoassays. Budesonide potently inhibited the production of bioactive IL-12. A significant suppression was obtained by treatment with even very low budesonide concentrations; even 10(-11) M budesonide significantly inhibited IL-12 to 81.6+/-7.6% of the control level (P<0.05). The maximal inhibitory effect of budesonide was seen at 10(-8) M. The inhibition of IL-12 production was significantly higher than the inhibition of GM-CSF (P<0.01) or IL-1beta (P<0.001). Whereas IL-12 production was totally inhibited, GM-CSF production was inhibited to 16.4+/-3.7 and IL-1beta production to 43.1+/-7.3% of control, respectively. The dramatic capacity of corticosteroids to modulate production of IL-12 as well as other cytokines may be a major mechanism underlying the effectiveness of these drugs in a broad spectrum of inflammatory diseases.
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PMID:Effects of a corticosteroid, budesonide, on production of bioactive IL-12 by human monocytes. 981 32

Budesonide and formoterol are extensively used in current asthma therapy. Budesonide is known as potent antiinflammatory agent and formoterol also appears to have some antiinflammatory properties. We investigated inhibitory effects of these drugs on eosinophil activation in vitro as induced by fibroblast-conditioned medium (FCM). We measured the modulation of expression of clonal designator (CD)11b and L-selectin with flow cytometry after 4 h or 16 h of culture of eosinophils when budesonide or formoterol was applied either directly to the eosinophils while they were stimulated with FCM (direct method) or when each drug was applied to lung fibroblasts from which conditioned medium was then administered to eosinophils (indirect method). In the direct method, budesonide (10(-)(8) M) inhibited the modulation of CD11b (44 [25th to 75th percentiles: 26 to 66]% of control) and L-selectin (30 [-13 to 48]% of control) only after 16 h, and not after 4 h. Formoterol did not directly inhibit the modulation of eosinophil CD11b and L-selectin expression. In the indirect method, both budesonide and formoterol inhibited lung fibroblast activation, resulting in diminished eosinophil activation after 4 h. Budesonide or formoterol at 10(-)(8) M inhibited upregulation of CD11b to 26 [15 to 40]% and 38 [23 to 46]%, respectively, and inhibited L-selectin shedding to 14 [-3 to 50]% and 27 [2 to 62]%, respectively, of control values. These results show that budesonide inhibits eosinophil activation primarily through effects on lung fibroblasts, presumably by inhibiting production of granulocyte-macrophage colony-stimulating factor. After longer incubation periods, budesonide also directly inhibits eosinophil activation. In contrast, formoterol can inhibit eosinophil activation only via inhibitory effects on lung fibroblasts. We did not observe an additional effect of formoterol, beyond the effects induced by budesonide under any circumstance studied. Lung fibroblasts, in addition to eosinophils, may serve as important target cells for antiinflammatory treatment in asthma.
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PMID:Effects of budesonide and formoterol on eosinophil activation induced by human lung fibroblasts. 1102 22