The p38 MAPK inhibitor SB203580 differentially modulates LPS-induced interleukin 6 expression in macrophages
| Autor: | Liu Zhengxiang, Fu Jianfeng, Ge Di, Hu Keyan, Ran Jihua, Shi Qinghai, Liping Cheng |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
MAPK/ERK pathway
Original Paper biology Lipopolysaccharide medicine.medical_treatment Immunology Macrophage-activating factor lipopolysaccharide interleukin 6 p38 macrophage Molecular biology Proinflammatory cytokine chemistry.chemical_compound Cytokine chemistry biology.protein medicine cytokine Immunology and Allergy Macrophage lipids (amino acids peptides and proteins) Signal transduction Interleukin 6 |
| Zdroj: | Central-European Journal of Immunology |
| ISSN: | 1426-3912 |
| Popis: | The p38 mitogen-activated protein kinase (MAPK) plays a key role in lipopolysaccharide (LPS)-induced signal transduction pathways that lead to inflammatory cytokine synthesis in macrophages; however, whether the inhibition of p38 MAPK regulates LPS-induced inflammatory cytokine expression in different types of macrophages remains the subject of debate. Herein, we assessed whether the inhibition of p38 MAPK by SB203580 regulates LPS-induced expression of the inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in RAW264.7 and resident peritoneal macrophages. Lipopolysaccharide stimulation of RAW264.7 macrophages or mouse resident peritoneal macrophages significantly increased TNF-α and IL-6 production. The addition of SB203580 to cultures dramatically blocked LPS-induced TNF-α production in RAW264.7 and mouse resident peritoneal macrophages, and dramatically blocked LPS-induced IL-6 production in RAW264.7 macrophages, but not in mouse resident peritoneal macrophages. Additionally, high concentrations of SB203580 resulted in increased IL-6 production. However, LPS-stimulation significantly up-regulated the mRNA transcript levels of TNF-α and IL-6 in RAW264.7 and mouse resident peritoneal macrophages, whereas pretreatment with SB203580 dramatically down-regulated LPS-induced mRNA transcript levels of TNF-α and IL-6 in these cells. Our data show that SB203580 differentially modulates LPS-induced production of the inflammatory cytokine IL-6 in two different sources of macrophages, and that this course of regulation occurs at the IL-6 mRNA post-transcriptional stage. |
| Databáze: | OpenAIRE |
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