A bis-malonic acid fullerene derivative significantly suppressed IL-33-induced IL-6 expression by inhibiting NF-κB activation

Megumi Funakoshi-Tago, Yurika Miyagawa, Fumihito Ueda, Tadahiko Mashino, Yasuhiro Moriwaki, Kenji Tago, Tadashi Kasahara, Hiroomi Tamura

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

IL-33 functions as a ligand for ST2L, which is mainly expressed in immune cells, including mast cells. IL-33 is a potent inducer of pro-inflammatory cytokines, such as IL-6, and has been implicated in the pathogenesis of allergic inflammatory diseases. Therefore, IL-33 has recently been attracting attention as a new target for the treatment of inflammatory diseases. In the present study, we demonstrated that a water-soluble bis-malonic acid fullerene derivative (C60-dicyclopropane-1,1,1′,1′-tetracarboxylic acid) markedly diminished the IL-33-induced expression of IL-6 in bone marrow-derived mast cells (BMMC). The bis-malonic acid fullerene derivative suppressed the canonical signaling steps required for NF-κB activation such as the degradation of IκBα and nuclear translocation of NF-κB by directly inhibiting the IL-33-induced IKK activation. Although p38 and JNK also contributed to IL-33-induced expression of IL-6, the bis-malonic acid fullerene derivative did not affect their activation. Furthermore, the bis-malonic acid fullerene derivative had no effect on the NF-κB activation pathway induced by TNFα and IL-1. These results suggest that the bis-malonic fullerene derivative has potential as a specific drug for the treatment of IL-33-induced inflammatory diseases by specifically inhibiting the NF-κB activation pathway.

Original languageEnglish
Pages (from-to)254-264
Number of pages11
JournalInternational Immunopharmacology
Volume40
DOIs
Publication statusPublished - 2016 Nov 1

Keywords

  • Bone marrow-derived mast cells
  • Fullerene
  • IL-33
  • IL-6
  • NF-κB

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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