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- Title
Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells.
- Authors
Wang, Yan-Ping; Wu, Yan; Li, Long-Yan; Zheng, Jin; Liu, Ren-Gang; Zhou, Jie-Ping; Yuan, Shi-Ying; Shang, You; Yao, Shang-Long
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
NONSTEROIDAL anti-inflammatory agents; MICROGLIA; LIPOXINS; ARACHIDONIC acid; CELL culture; CYTOKINES; IMMUNOREGULATION; CELL metabolism; PROTEIN metabolism; LIPOPOLYSACCHARIDES; PROTEINS; BIOCHEMISTRY; RESEARCH; INFLAMMATION; ANIMAL experimentation; RESEARCH methodology; INTERLEUKIN-1; MEDICAL cooperation; EVALUATION research; EICOSANOIDS; PHENOMENOLOGY; COMPARATIVE studies; CELLS; ASPIRIN; DNA-binding proteins; TRANSFERASES; TUMOR necrosis factors; OXIDOREDUCTASES; CELL lines; NITRIC oxide; MICE; PHARMACODYNAMICS
- Publication
Journal of Neuroinflammation, 2011, Vol 8, Issue 1, p95
- ISSN
1742-2094
- Publication type
journal article
- DOI
10.1186/1742-2094-8-95