A novel immunomodulatory effect of ugonin U in human neutrophils via stimulation of phospholipase C

Chun Yu Chen, Chih Chuang Liaw, Yi Hsuan Chen, Wen Yi Chang, Pei Jen Chung, Tsong Long Hwang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

33 Scopus citations

Abstract

Neutrophils have a crucial role in the immune system and are the first line of defense against pathogenic invaders. Neutrophil activation is required for their defensive function and can be induced by diverse stimuli, through either binding to cell surface receptors or direct intracellular target molecule stimulation. In this study, we found that 4″a,5″,6″,7″, 8″,8″a-hexahydro-5,3′,4′-trihydroxy-5″,5″, 8″a-trimethyl-4H-chromeno [2″,3″:7,6]flavone (ugonin U), a flavonoid isolated from Helminthostachys zeylanica (L) Hook, significantly induced superoxide production and release in a time- and concentration-dependent manner. A series of experiments was performed to dissect the mechanism of ugonin U-induced respiratory burst in human neutrophils. Our results demonstrated that ugonin U induced a slow increase in intracellular Ca 2+, which was necessary for ugonin U-stimulated superoxide release. Use of a formyl peptide receptor (FPR) blocker, G protein inhibitor, and protein tyrosine kinase (PTK) inhibitor proved that FPR, G proteins, and PTKs were not associated with ugonin U-induced respiratory burst. Additionally, immunoblotting results revealed that ugonin U did not affect the phosphorylation of mitogen-activated protein kinases and protein tyrosine. Nevertheless, a phospholipase C (PLC) inhibitor and an inositol triphosphate (IP3) receptor antagonist considerably suppressed ugonin U-stimulated Ca2+ mobilization and subsequent superoxide release. Ugonin U also induced an increase in intracellular IP3 formation, which could be blocked using a PLC inhibitor. In conclusion, our study reveals that ugonin U represents the first identified natural flavonoid compound to directly stimulate PLC. Moreover, ugonin U induces respiratory burst via the PLC/IP3/Ca2+ pathway in human neutrophils.

Original languageEnglish
Pages (from-to)222-231
Number of pages10
JournalFree Radical Biology and Medicine
Volume72
DOIs
StatePublished - 07 2014

Keywords

  • Flavonoid
  • Free radicals
  • Helminthostachys zeylanica
  • Neutrophils
  • Phospholipase C
  • Superoxide
  • Ugonin U

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