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

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.

• Authors: 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 Ikematsu, Yutaka Suzuki, Katsumi Tanaka, Paul Martin, Isao Shimokawa, Ryoichi Mori
• Journal: EMBO molecular medicine (EMBO Mol Med) Vol. 10 Issue 10 (10 2018) ISSN: 1757-4684 [Electronic] England
• PMID: 30171089 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Chemical References

• MIRN223 microRNA, human
• MIRN223 microRNA, mouse
• MicroRNAs

Topics

• Animals
• Cells, Cultured
• Humans
• Inflammation (physiopathology)
• Mice
• Mice, Knockout
• MicroRNAs (genetics, metabolism)
• Neutrophils (immunology)
• Staphylococcal Infections (physiopathology)
• Staphylococcus aureus (immunology)
• Wound Infection (physiopathology)