EMBO Molecular Medicine (Oct 2018)
Targeting miR‐223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds
- Maiko deKerckhove,
- 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
Affiliations
- Maiko deKerckhove
- Department of Pathology Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- Katsuya Tanaka
- Department of Pathology Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- Takahiro Umehara
- Department of Forensic Pathology and Science Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- Momoko Okamoto
- Department of Pathology Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- Sotaro Kanematsu
- Laboratory of Functional Genomics Department of Medical Genome Science Graduate of Frontier Science The University of Tokyo Tokyo Japan
- Hiroko Hayashi
- Department of Pathology Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- Hiroki Yano
- Department of Plastic and Reconstructive Surgery Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- Soushi Nishiura
- Department of Pathology Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- Shiho Tooyama
- Department of Pathology Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- Yutaka Matsubayashi
- Schools of Biochemistry and Physiology Pharmacology & Neuroscience Faculty of Biomedical Sciences University of Bristol Bristol UK
- Toshimitsu Komatsu
- Department of Pathology Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- Seongjoon Park
- Department of Pathology Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- Yuka Okada
- Department of Ophthalmology Wakayama Medical University Wakayama Japan
- Rina Takahashi
- Faculty of Pharmaceutical Sciences Tokyo University of Science Chiba Japan
- Yayoi Kawano
- Faculty of Pharmaceutical Sciences Tokyo University of Science Chiba Japan
- Takehisa Hanawa
- Faculty of Pharmaceutical Sciences Tokyo University of Science Chiba Japan
- Keisuke Iwasaki
- Department of Pathology Sasebo City General Hospital Sasebo Nagasaki Japan
- Tadashige Nozaki
- Department of Pharmacology Faculty of Dentistry Osaka Dental University Hirakata Osaka Japan
- Hidetaka Torigoe
- Department of Applied Chemistry Faculty of Science Tokyo University of Science Tokyo Japan
- Kazuya Ikematsu
- Department of Forensic Pathology and Science Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- Yutaka Suzuki
- Laboratory of Functional Genomics Department of Medical Genome Science Graduate of Frontier Science The University of Tokyo Tokyo Japan
- Katsumi Tanaka
- Department of Plastic and Reconstructive Surgery Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- Paul Martin
- Schools of Biochemistry and Physiology Pharmacology & Neuroscience Faculty of Biomedical Sciences University of Bristol Bristol UK
- Isao Shimokawa
- Department of Pathology Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- Ryoichi Mori
- Department of Pathology Nagasaki University School of Medicine and Graduate School of Biomedical Sciences Nagasaki Japan
- DOI
- https://doi.org/10.15252/emmm.201809024
- Journal volume & issue
-
Vol. 10,
no. 10
pp. n/a – n/a
Abstract
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.
Keywords