Korean J Anesthesiol.  2020 Apr;73(2):151-157. 10.4097/kja.19233.

Effect of BMS-470539 on lipopolysaccharide-induced neutrophil activation

Affiliations
  • 1Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School & Hospital, Gwangju, Korea
  • 2Brain Korea 21 Project, Center for Creative Biomedical Scientists at Chonnam National University, Gwangju, Korea
  • 3Department of Anesthesiology and Pain Medicine, Gwangju Christian Hospital, Gwangju, Korea

Abstract

Background
BMS-470539, a recently introduced selective agonist of the melanocortin 1 receptor, is known to have anti-inflammatory properties. In this study, we investigated the effects of BMS-470539 on lipopolysaccharide (LPS)-induced inflammatory responses and delayed apoptosis with its signaling pathways in human neutrophils.
Methods
Isolated human neutrophils were incubated with various concentrations of BMS-470539 (1, 10, and 100 µM) in the presence or absence of LPS (100 ng/ml), and the expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β, were assessed. The effects of BMS-470539 on the expression of mitogen-activated protein kinases (MAPKs), such as p38, extracellular-signal-regulated kinase 1/2, and c-Jun N-terminal kinase, and the expression of nuclear factor kappa B (NF-κB) in LPS-stimulated human neutrophils, were evaluated by enzyme-linked immunosorbent assay. Neutrophil apoptosis was also measured by fluorescence-activated cell sorting (annexin V/propidium iodide) in LPS-stimulated neutrophils under treatment with BMS-470539.
Results
BMS-470539 attenuated LPS-induced expression of pro-inflammatory cytokines, and phosphorylation of MAPKs and NF-κB. LPS stimulation reduced neutrophil apoptosis compared to the controls; however, BMS-470539 significantly inhibited the reduction of neutrophil apoptosis.
Conclusions
BMS-470539 can suppress the inflammatory responses of LPS-stimulated neutrophils by inhibition of MAPK pathways or NF-κB pathway, and it can also inhibit LPS-delayed neutrophil apoptosis.

Keyword

Apoptosis; BMS-470539; Cytokines; Lipopolysaccharides; Mitogen-activated protein kinases; Neutrophils; NF-kappa B
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