Targeting miR-223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds

Maiko de Kerckhove, Katsuya Tanaka, Takahiro Umehara, Momoko Okamoto, Sotaro Kanematsu, Hiroko Hayashi, Hiroki Yano, Soushi Nishiura, Shiho Tooyama, Yutaka Matsubayashi, Toshimitsu Komatsu, Seongjoon Park, Yuka Okada, Rina Takahashi, Yayoi Kawano, Takehisa Hanawa, Keisuke Iwasaki, Tadashige Nozaki, Hidetaka Torigoe, Kazuya IkematsuYutaka Suzuki, Katsumi Tanaka, Paul Martin, Isao Shimokawa, Ryoichi Mori*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

12 Citations (Scopus)
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Abstract

Argonaute 2 bound mature microRNA (Ago2-miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation-related Ago2-miRNAs (miR-139-5p, miR-142-3p, miR-142-5p, and miR-223) and show that miR-223 is critical for infection control. miR-223Y/− mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin-6 expression, and markedly improved repair of Staphylococcus aureus-infected wounds. We also showed that the expression of miR-223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miR-223Y/−-derived neutrophils, or miR-223 antisense oligodeoxynucleotides in S. aureus-infected wild-type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miR-223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miR-223 might be of therapeutic benefit for infected wounds in the clinic.

Original languageEnglish
Article numbere9024
Number of pages21
JournalEMBO Molecular Medicine
Volume10
Issue number10
Early online date31 Aug 2018
DOIs
Publication statusPublished - 1 Oct 2018

Keywords

  • inflammation
  • miR-223
  • neutrophil
  • skin wound healing
  • Staphylococcus aureus

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