Regulation of eotaxin-3/CCL26 expression in human monocytic cells
Autor: | Christopher Power, Victoria E. L. Stubbs, Kamala D. Patel |
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Rok vydání: | 2010 |
Předmět: |
CCR1
CCR2 Chemokine Immunology Blotting Western Interleukin-1beta Gene Expression Enzyme-Linked Immunosorbent Assay Monocytes Interferon-gamma medicine Immunology and Allergy Humans STAT6 Regulation of gene expression biology Chemistry Chemokine CCL26 Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Monocyte U937 Cells Original Articles Molecular biology medicine.anatomical_structure Gene Expression Regulation Chemokines CC biology.protein Tumor necrosis factor alpha Interleukin-4 Signal transduction Signal Transduction |
Zdroj: | Immunology. 130(1) |
ISSN: | 1365-2567 |
Popis: | Eotaxin-3/CCL26 is an agonist for chemokine receptor 3 (CCR3) and a natural antagonist for CCR1, CCR2 and CCR5. CCL26 expression by non-haematopoietic cells has been well documented; however, no studies to date have demonstrated CCL26 expression by leucocytes. In this study, we investigated the ability of human monocytic cells to produce CCL26 in response to cytokines. We found that interleukin-4 (IL-4) increased the expression of CCL26 messenger RNA (mRNA) and protein in U937 cells, in human monocytes and in human monocyte-derived macrophages. Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) alone did not induce CCL26 expression, yet these pro-inflammatory cytokines synergized with IL-4 to increase CCL26 protein expression. Signal transducer and activator of transcription 6 (STAT6) was not affected by costimulation with TNF-alpha, suggesting that the synergy between IL-4 and TNF-alpha occurs at a step downstream of STAT6 activation. Co-incubation of interferon-gamma (IFN-gamma) with IL-4 had no effect on CCL26 protein release. By contrast, pretreatment with IFN-gamma decreased total STAT6 protein, blocked IL-4-mediated STAT6 phosphorylation and decreased IL-4-mediated CCL26 mRNA expression and protein release. These data show that IL-4 and pro-inflammatory cytokines such as TNF-alpha, IL-1beta and IFN-gamma regulate CCL26 synthesis in human monocytic cells, which may be important in regulating monocyte inflammatory responses. |
Databáze: | OpenAIRE |
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