Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells
| Autor: | Longyan Li, Yan Wu, You Shang, Jin Zheng, Yan-Ping Wang, Jie-Ping Zhou, Shi-ying Yuan, Ren-Gang Liu, Shanglong Yao |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
MAPK/ERK pathway
Lipopolysaccharides medicine.medical_specialty medicine.medical_treatment p38 mitogen-activated protein kinases Interleukin-1beta Immunology Nitric Oxide Synthase Type II Pharmacology Nitric Oxide lcsh:RC346-429 Nitric oxide Cell Line chemistry.chemical_compound Mice Cellular and Molecular Neuroscience Internal medicine medicine Animals lcsh:Neurology. Diseases of the nervous system Inflammation biology Aspirin Kinase Tumor Necrosis Factor-alpha General Neuroscience Research Anti-Inflammatory Agents Non-Steroidal NF-kappa B NF-κB Nitric oxide synthase Enzyme Activation Lipoxins Transcription Factor AP-1 Cytokine Endocrinology chemistry Neurology biology.protein Tumor necrosis factor alpha Microglia Mitogen-Activated Protein Kinases |
| Zdroj: | Journal of Neuroinflammation Journal of Neuroinflammation, Vol 8, Iss 1, p 95 (2011) |
| ISSN: | 1742-2094 |
| DOI: | 10.1186/1742-2094-8-95 |
| Popis: | Background Microglial activation plays an important role in neurodegenerative diseases through production of nitric oxide (NO) and several pro-inflammatory cytokines. Lipoxins (LXs) and aspirin-triggered LXs (ATLs) are considered to act as 'braking signals' in inflammation. In the present study, we investigated the effect of aspirin-triggered LXA4 (ATL) on infiammatory responses induced by lipopolysaccharide (LPS) in murine microglial BV-2 cells. Methods BV-2 cells were treated with ATL prior to LPS exposure, and the effects of such treatment production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) were analysed by Griess reaction, ELISA, western blotting and quantitative RT-PCR. Moreover, we investigated the effects of ATL on LPS-induced nuclear factor-κB (NF-κB) activation, phosphorylation of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) activation. Results ATL inhibited LPS-induced production of NO, IL-1β and TNF-α in a concentration-dependent manner. mRNA expressions for iNOS, IL-1β and TNF-α in response to LPS were also decreased by ATL. These effects were inhibited by Boc-2 (a LXA4 receptor antagonist). ATL significantly reduced nuclear translocation of NF-κB p65, degradation of the inhibitor IκB-α, and phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK in BV-2 cells activated with LPS. Furthermore, the DNA binding activity of NF-κB and AP-1 was blocked by ATL. Conclusions This study indicates that ATL inhibits NO and pro-inflammatory cytokine production at least in part via NF-κB, ERK, p38 MAPK and AP-1 signaling pathways in LPS-activated microglia. Therefore, ATL may have therapeutic potential for various neurodegenerative diseases. |
| Databáze: | OpenAIRE |
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