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)

Chronic sinusitis and its associated eosinophilic infiltrate are believed to be mediated, at least in part, by the upregulation of Th-2 cytokines, including interleukin-4, interleukin-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Interleukin-4 is involved in IgE production and in eosinophil recruitment through upregulation of vascular cell adhesion molecule-1. Interleukin-5 and GM-CSF are involved in eosinophil growth and survival. The aim of this study was to investigate the expression of receptors for these cytokines in the sinus mucosa of subjects with chronic sinusitis. Using the technique of in situ hybridization to detect specific cytokine receptor messenger RNA, we studied the sinus mucosa of subjects with nonallergic chronic sinusitis, subjects with allergic chronic sinusitis, subjects with allergic chronic sinusitis treated with topical steroids, and normal controls. Our data demonstrate higher expression of interleukin-4 receptor in subjects with allergic chronic sinusitis than in controls (p < 0.001) and higher expression of interleukin-5 receptor in both subjects with nonallergic chronic sinusitis and subjects with allergic chronic sinusitis than in controls (p < 0.001, p < 0.001). The expression of interleukin-4 receptor and interleukin-5 receptor was higher in subjects with allergic chronic sinusitis than in subjects with nonallergic chronic sinusitis (p < 0.001). GM-CSF receptor expression was also found to be higher in subjects with allergic chronic sinusitis and subjects with nonallergic chronic sinusitis than in controls (p < 0.001, p < 0.001). In contrast to interleukin-4 receptor and interleukin-5 receptor, however, expression of GM-CSF receptor was higher in subjects with nonallergic chronic sinusitis than in subjects with allergic chronic sinusitis (p < 0.001). In subjects with allergic chronic sinusitis treated with topical corticosteroids, the expression of interleukin-4 receptor and interleukin-5 receptor messenger RNA levels was significantly lower than levels in patients with allergic chronic sinusitis who were not taking topical steroids (p < 0.001, p < 0.001). Steroid treatment had no effect on GM-CSF receptor messenger RNA expression. In conclusion, our data support a role for Th-2 cytokine receptors in the pathophysiology of chronic sinusitis. Further, our data lend support to the theory that differential activation of distinct cytokine pathways mediates inflammation in chronic sinusitis depending on whether there is associated allergy. Finally, treatment with topical corticosteroids has been demonstrated in chronic sinusitis to downregulate receptors for interleukin-4 and interleukin-5.
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PMID:Interleukin-4, interleukin-5, and granulocyte-macrophage colony-stimulating factor receptor expression in chronic sinusitis and response to topical steroids. 956 Jan 1

The purpose of this study was to compare the expression of cytokines and nuclear factor-kappa B (NF-kappa B) subunits in cultured sinus mucosal cells by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in chronic sinusitis patients with allergic rhinitis (abbreviated as AR patients) versus patients without AR (abbreviated as non-AR patients). The localization of p50 in cultured sinus mucosal cells was also observed by immunocytochemistry. The expression of messenger RNAs (mRNA) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-8, p50 and p65 subunits, and inhibitory kappa B-alpha (I kappa B-alpha) were analyzed by RT-PCR. The proportion of active NF-kappa B-positive cells in the epithelial layer was analyzed using a laser-scanning confocal microscope image system. The levels of GM-CSF, IL-6, IL-8, and p50 mRNAs in AR patients were significantly higher than those in non-AR patients (p < 0.01, p < 0.01, p < 0.01, and p < 0.001, respectively). Immunocytochemical reaction for p50 in sinus mucosal cells in AR patients showed more intense nuclear staining compared to non-AR patients. These findings could support the hypothesis that the increase of cytokines from sinus mucosal cells in AR patients was associated with augmented NF-kappa B mRNA expression, resulting in the modification of the cytokine network.
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PMID:Expression and localization of nuclear factor-kappa B subunits in cultured human paranasal sinus mucosal cells. 1286 72

The development of chronic sinusitis is a complex multifactorial process characterized by inflammation of nasal and sinus mucosa. Many studies have shown that the composition of the inflammatory substrate in chronic sinusitis is similar to that seen in allergic rhinitis and in the late-phase response to antigen challenge. Mononuclear cells, consisting of T and B lymphocytes and activated eosinophils, are prominent in the sinus mucosa of patients with chronic sinusitis, especially in atopic patients. Cellular recruitment and activation of the inflammatory infiltrate have been largely attributed to the effects of T(H)2 cytokines (namely interleukin -4, IL-5, IL-13, and granulocyte-macrophage colony-stimulating factor). Current treatment of allergic chronic sinusitis consists of nasal corticosteroids and immunotherapy. A subgroup of steroid-insensitive patients demonstrates an overexpression of a variant of the glucocorticoid receptor (GR). Despite these advances, the management and treatment of chronic sinusitis is often fraught with failures and remains a frustrating task for both physician and patient.
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PMID:Molecular immunology and immunotherapy for chronic sinusitis. 1453 72