Simultaneous induction of autophagy and toll-like receptor signaling pathways by graphene oxide

Guan-Yu Chen, Hong Jie Yang, Chia Hsin Lu, Yu Chan Chao, Shiaw Min Hwang, Chiu Ling Chen, Kai Wei Lo, Li Yu Sung, Wen Yi Luo, Hsing Yu Tuan, Yu Chen Hu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

163 Scopus citations

Abstract

Graphene oxide (GO) nanosheets have sparked growing interests in biological and medical applications. This study examined how macrophage, the primary immune cell type engaging microbes, responded to GO treatment. We uncovered that incubation of macrophage cell RAW264.7 with GO elicited autophagy in a concentration-dependent manner, as evidenced by the appearance of autophagic vacuoles and activation of autophagic marker proteins. Such GO-induced autophagy was observed in various cell lines and in macrophage treated with GO of different sizes. Strikingly, GO treatment of macrophage provoked the toll-like receptor (TLR) signaling cascades and triggered ensuing cytokine responses. Molecular analysis identified that TLR4 and TLR9 and their downstream signaling mediators MyD88, TRAF6 and NF-κB played pivotal roles in the GO-induced inflammatory responses. By silencing individual genes in the signaling pathway, we further unveiled that the GO-induced autophagy was modulated by TLR4, TLR9 and was dependent on downstream adaptor proteins MyD88, TRIF and TRAF6. Altogether, we demonstrated that GO treatment of cells simultaneously triggers autophagy and TLR4/TLR9-regulated inflammatory responses, and the autophagy was at least partly regulated by the TLRs pathway. This study thus suggests a mechanism by which cells respond to nanomaterials and underscores the importance of future safety evaluation of nanomaterials.

Original languageEnglish
Pages (from-to)6559-6569
Number of pages11
JournalBiomaterials
Volume33
Issue number27
DOIs
StatePublished - 1 Sep 2012

Keywords

  • Autophagy
  • Graphene oxide
  • Nanomaterials
  • Signal transduction
  • Toll-like receptor

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