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 eosinophils are known to lose Ia antigen expression as they mature, and, accordingly, eosinophils obtained from the blood of five eosinophilic donors and three of four normal donors failed to display the major histocompatibility complex class II antigen HLA-DR, as determined by flow cytometry. However, when eosinophils from these nine donors were maintained in culture with recombinant human granulocyte-macrophage colony-stimulating factor and murine 3T3 fibroblasts, HLA-DR consistently developed on the eosinophils. By days 4-6 of culture, 24-97% of eosinophils were HLA-DR+, and the eosinophils remained morphologically mature. In contrast, another class II antigen, HLA-DQ, was not detectable by flow cytometry on eosinophils from eight of nine donors. Cultured eosinophils were able to synthesize HLA-DR, as documented by the incorporation of [35S]methionine into immunoprecipitable HLA-DR heavy and light chains. These findings show that mature eosinophils can synthesize and express HLA-DR and provide a means whereby eosinophils may interact with CD4+ lymphocytes.
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PMID:Mature human eosinophils have the capacity to express HLA-DR. 291 83

Invariant chain (Ii) plays an important role in major histocompatibility complex (MHC) class II antigen processing and presentation and is constitutively synthesized in B lymphocytes, in macrophages, dendritic cells and in some epithelial cells. It has been shown that interferon-gamma, tumour necrosis factor-alpha and interleukin-4 co-regulate Ii and MHC class II expression in various cell types. We describe here a novel regulation of Ii expression in macrophages. Treatment of the premature monocytic cell lines WEHI 265.1, M1 and WEHI-3B with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) strongly enhances Ii expression while class II expression is not induced. In contrast, GM-CSF did not enhance Ii in mature macrophage cell lines. The increase of Ii expression in WEHI 265.1 cells takes several days. This long induction time, and a difference in activity between GM-CSF-conditioned medium and GM-CSF, together suggest that GM-CSF stimulates WEHI 265.1 cells to secrete a factor that modulates Ii expression. These results may imply a class II-independent function of Ii, which we discuss in this paper.
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PMID:Granulocyte-macrophage colony-stimulating factor elevates invariant chain expression in immature myelomonocytic cell lines. 920 74

HLA class I and II molecules play a central role in regulating host immune responses against microbial infections because they present foreign antigens to CD8+ and CD4+ T lymphocytes, respectively. Many cytokines, especially interferons (IFN), are known to upregulate human leucocyte antigen (HLA) class I and II gene expression, but the kinetics, expression levels and viral regulation of HLA genes in primary human cells have not been well documented. Stimulation of peripheral blood mononuclear cells (PBMC) with IFN-alpha and IFN-gamma resulted in a 1.5- to twofold increase in HLA class I and beta 2-microglobulin expression in lymphocytes and monocytes. Lymphocytes did not express any detectable HLA class II either basally or after IFN induction. In monocytes, instead, a high basal class II expression was found and it was further induced by IFN-alpha (up to twofold) and especially by IFN-gamma (up to fivefold). In granulocyte-macrophage colony-stimulating factor (GM-CSF) differentiated human macrophages, basal HLA class I and II protein expression levels were high but IFN-gamma stimulation was able to further enhance their expression. Accordingly, class I and II mRNA expression was elevated by IFN-gamma, whereas IFN-alpha practically had no effect on HLA class I mRNA levels. Influenza A virus infection of macrophages resulted in temporary increases in HLA class I, beta 2-microglobulin and class II antigen expression. Neutralization of virus-induced IFN production by antibodies against type I and II IFNs prevented the virus-induced upregulation of HLA antigens. At late times of infection, as analysed by steady-state mRNA expression, both HLA class I and II mRNA were strongly reduced. These results suggest that IFNs are important regulators of HLA genes and responsible for a temporary increase in HLA antigen expression during influenza A virus infection.
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PMID:Regulation of HLA class I and II expression by interferons and influenza A virus in human peripheral blood mononuclear cells. 930 32

DNA vaccines containing genes for antigenic portions of viruses have recently been developed as a novel vaccination technology. Direct injection of plasmid DNA in vivo results in prolonged expression of viral proteins and may, thus, mimic the action of attenuated vaccines. An important advantage of this vaccination method is that in vivo-synthesized viral proteins can enter both major histocompatibility complex (MHC) class I and class II antigen-processing pathways to activate specific immunization. In many animal models for infectious diseases, DNA vaccines induced a broad range of immune responses, including antibody, CD8+ cytotoxic T lymphocytes (CTL) and CD4+ helper T (Th) lymphocyte responses, and protective immunity against challenge with the pathogen. The magnitude and nature of these immune responses to DNA vaccines can be further manipulated by codelivery of cytokine genes. Summarizing the many studies reported to date, we can draw conclusions regarding the adjuvant effects of these cytokine genes on DNA vaccines. Coadministration of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-2 genes induces higher antibody titers and T-cell proliferation responses than other cytokine genes tested to date. In contrast, the CTL activity is only modestly increased by the GM-CSF and IL-2 genes. The IL-12 gene polarizes the immune responses to DNA vaccines toward Th1 cell development and stimulates the strongest CTL activity. In contrast, co-injection of the IL-4 gene promotes the development of Th2 cells and increases production of antibodies, but suppresses CTL activity. Thus, the immune responses to DNA vaccines can be engineered by co-injection of an appropriate cytokine gene to favor the formation of either CTL or neutralization antibodies and, therefore, provide the best protection against a particular pathogen.
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PMID:Modulation of immune responses to DNA vaccines by codelivery of cytokine genes. 1070 87