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The Effect of Caffeic Acid Phenethyl Ester (CAPE) on Phagocytic activity of septic Neutrophil in vitro

  • Eun-A Jang (Department of Anesthesiology and Pain Medicine, School of Dentistry, Chonnam National University & Chonnam National University Hospital) ;
  • Hui-Jing Han (Brain Korea 21 Project, Center for Creative Biomedical Scientists at Chonnam National University) ;
  • Tran Duc Tin (Brain Korea 21 Project, Center for Creative Biomedical Scientists at Chonnam National University) ;
  • Eunye Cho (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School & Hospital) ;
  • Seongheon Lee (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School & Hospital) ;
  • Sang Hyun Kwak (Brain Korea 21 Project, Center for Creative Biomedical Scientists at Chonnam National University)
  • 투고 : 2023.10.19
  • 심사 : 2023.12.08
  • 발행 : 2023.12.31

초록

Caffeic acid phenethyl ester (CAPE) is an active component of propolis obtained from honeybee hives. CAPE possesses anti-mitogenic, anti-carcinogenic, anti-inflammatory, and immunomodulatory activities in diverse systems, which know as displays antioxidant activity and inhibits lipoxygenase activities, protein tyrosine kinase, and nuclear factor kappa B (NF-κB) activation. This study aimed to investigate the effect of CAPE on lipopolysaccharide (LPS)-induced human neutrophil phagocytosis. Human neutrophils were cultured with various concentrations of CAPE (1, 10, and 100 µM) with or without LPS. The pro-inflammatory proteins (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6 and IL-8) levels were measured after 4 h incubation. To investigate the intracellular signaling pathway, we measured the levels of mitogen-activated protein kinases (MAPK), including phosphorylation of p38, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Next, to evaluate the potential phagocytosis, neutrophils were labeled with iron particles of superparamagnetic iron oxide nanoparticles (SPIONs, 40 nm) for 1 h in culture medium containing 5 mg/mL of iron. The labeling efficiency was determined by Prussian blue staining for intracellular iron and 3T-wighted magnetic resonance imaging. CAPE decreased the activation of intracellular signaling pathways, including ERK1/2 and c-Jun, and expression of pro-inflammatory cytokines, including TNF-α and IL-6, but had no effect on the signaling pathways of p38 and cytokine IL-8. Furthermore, images obtained after mannan-coated SPION treatment suggested that CAPE induced significantly higher signal intensities than the control or LPS group. Together, these results suggest that CAPE regulates LPS-mediated activation of human neutrophils to reduce phagocytosis.

키워드

과제정보

This study was supported by a grant (CRI12051-21) Chonnam National University Hospital research institute of clinical medicine.

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