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Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells.

Abstract

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.

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  • Authors+Show Affiliations

    ,

    Department of Anesthesiology and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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    Source

    Journal of neuroinflammation 8: 2011 Aug 10 pg 95

    MeSH

    Animals
    Anti-Inflammatory Agents, Non-Steroidal
    Aspirin
    Cell Line
    Enzyme Activation
    Inflammation
    Interleukin-1beta
    Lipopolysaccharides
    Lipoxins
    Mice
    Microglia
    Mitogen-Activated Protein Kinases
    NF-kappa B
    Nitric Oxide
    Nitric Oxide Synthase Type II
    Transcription Factor AP-1
    Tumor Necrosis Factor-alpha

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21831303

    Citation

    Wang, Yan-Ping, et al. "Aspirin-triggered Lipoxin A4 Attenuates LPS-induced Pro-inflammatory Responses By Inhibiting Activation of NF-κB and MAPKs in BV-2 Microglial Cells." Journal of Neuroinflammation, vol. 8, 2011, p. 95.
    Wang YP, Wu Y, Li LY, et al. Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells. J Neuroinflammation. 2011;8:95.
    Wang, Y. P., Wu, Y., Li, L. Y., Zheng, J., Liu, R. G., Zhou, J. P., ... Yao, S. L. (2011). Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells. Journal of Neuroinflammation, 8, p. 95. doi:10.1186/1742-2094-8-95.
    Wang YP, et al. Aspirin-triggered Lipoxin A4 Attenuates LPS-induced Pro-inflammatory Responses By Inhibiting Activation of NF-κB and MAPKs in BV-2 Microglial Cells. J Neuroinflammation. 2011 Aug 10;8:95. PubMed PMID: 21831303.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells. AU - Wang,Yan-Ping, AU - Wu,Yan, AU - Li,Long-Yan, AU - Zheng,Jin, AU - Liu,Ren-Gang, AU - Zhou,Jie-Ping, AU - Yuan,Shi-Ying, AU - Shang,You, AU - Yao,Shang-Long, Y1 - 2011/08/10/ PY - 2011/03/24/received PY - 2011/08/10/accepted PY - 2011/8/12/entrez PY - 2011/8/13/pubmed PY - 2012/2/24/medline SP - 95 EP - 95 JF - Journal of neuroinflammation JO - J Neuroinflammation VL - 8 N2 - 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. SN - 1742-2094 UR - https://www.unboundmedicine.com/medline/citation/21831303/Aspirin_triggered_lipoxin_A4_attenuates_LPS_induced_pro_inflammatory_responses_by_inhibiting_activation_of_NF_κB_and_MAPKs_in_BV_2_microglial_cells_ L2 - https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-8-95 DB - PRIME DP - Unbound Medicine ER -