Aspirin-triggered lipoxin A4attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells

Abstract

BackgroundMicroglial 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.MethodsBV-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.ResultsATL 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.ConclusionsThis 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.

Aspirin attenuates angiotensin II-induced inflammation in bone marrow mesenchymal stem cells via the inhibition of ERK1/2 and NF-κB activation

“…It was reported that aspirin inhibits the activation of ERK1/2 and inflammatory responses in a series of pathophysiological conditions (17,18). In the present study, we observed that aspirin (0.1 mM) significantly inhibited the AngII-induced activation of ERK1/2 in bmMSCs.…”

ResolvinD1 reduces apoptosis and inflammation in primary human alveolar epithelial type 2 cells

“…This finding is consistent with the anti-inflammatory effects of another type of SPM (aspirin-triggered lipoxin A 4 ) used in our previous study. 42 However, in macrophages, 17R-RvD1 and RvD1 regulates LPS-induced primary human macrophage production of IL-7, IL-12p70, GM-CSF, IL-8, CCL2, and MIP-1α without reducing that of IL-6 and IL-10. 43 It is well known that the activation of the transcription factor NF-κB regulates numerous genes that function in innate and adaptive immunity and the inflammatory response.…”

“…44 There is extensive evidence that SPMs exhibit their anti-inflammatory effects through the inhibition of the NF-κB pathway. 42,45 IκBs are major regulators of NF-κB activity and are involved in the feedback inhibition of NF-κB. RvD1 markedly decreased airway eosinophilia and mucus metaplasia during allergic airway inflammation, in part, by decreasing IL-5 and IκBα degradation.…”

Inhibition of Nitric Oxide and Prostaglandin E₂ Expression by Methanol Extract of <i>Polyopes affinis</i> in Lipopolysaccharide-stimulated BV2 Microglial Cells through Suppression of Akt-dependent NF-kB Activity and MAPK Pathway

“…However, there are several inconsistencies in the expression of proteins of the MAPK family such as ERK, p38 and JNK. Reports suggest that ERK and p38 are essential for regulating LPS-induced NF-κB activation [23,24]. Other investigations revealed the crucial effects of JNK on inducing pro-inflammatory mediators via the NF-κB pathway [25,26].…”