5 years ago

Sodium salicylate modulates inflammatory responses through AMP-activated protein kinase activation in LPS-stimulated THP-1 cells

Sodium salicylate modulates inflammatory responses through AMP-activated protein kinase activation in LPS-stimulated THP-1 cells
Jian Li, Yaru Luo, Wei Mei, Xi Wu, Dan Wang, Weiwei Bao
Sodium salicylate (NaSal) is a nonsteroidal anti-inflammatory drug. The putative mechanisms for NaSal's pharmacologic actions include the inhibition of cyclooxygenases, platelet-derived thromboxane A2, and NF-κB signaling. Recent studies demonstrated that salicylate could activate AMP-activated protein kinase (AMPK), an energy sensor that maintains the balance between ATP production and consumption. The anti-inflammatory action of AMPK has been reported to be mediated by promoting mitochondrial biogenesis and fatty acid oxidation. However, the exact signals responsible for salicylate-mediated inflammation through AMPK are not well-understood. In the current study, we examined the potential effects of NaSal on inflammation-like responses of THP-1 monocytes to lipopolysaccharide (LPS) challenge. THP-1 cells were stimulated with or without 10 ug/mL LPS for 24 h in the presence or absence of 5 mM NaSal. Apoptosis was measured by flow cytometry using Annexin V/PI staining and by Western blotting for the Bcl-2 anti-apoptotic protein. Cell proliferation was detected by EdU incorporation and by Western blot analysis for proliferating cell nuclear antigen (PCNA). Secretion of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) was determined by enzyme-linked immunosorbent assay (ELISA). We observed that the activation of AMPK by NaSal was accompanied by induction of apoptosis, inhibition of cell proliferation, and increasing secretion of TNF-α and IL-1β. These effects were reversed by Compound C, an inhibitor of AMPK. In addition, NaSal/AMPK activation inhibited LPS-induced STAT3 phosphorylation, which was reversed by Compound C treatment. We conclude that AMPK activation is important for NaSal-mediated inflammation by inducing apoptosis, reducing cell proliferation, inhibiting STAT3 activity, and producing TNF-α and IL-1β. AMPK activation is important for NaSal-mediated inflammatory response in LPS-stimulated THP-1 cells by inducing apoptosis, reducing cell proliferation, increasing TNF-α and IL-1β secretions, and blocking STAT3 activity. The anti-inflammatory effects of NaSal are partly mediated by AMPK.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jcb.26249

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