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

Authors: de Kerckhove, M., Tanaka, K., Umehara, T., Okamoto, M., Kanematsu, S., Hayashi, H., Yano, H., Nishiura, S., Tooyama, S., Matsubayashi, Y., Komatsu, T., Park, S., Okada, Y., Takahashi, R., Kawano, Y., Hanawa, T., Iwasaki, K., Nozaki, T., Torigoe, H., Ikematsu, K., Suzuki, Y., Tanaka, K., Martin, P., Shimokawa, I., Mori, R.

Journal: EMBO Molecular Medicine

Publication Date: 01/10/2018

Volume: 10

Issue: 10

eISSN: 1757-4684

ISSN: 1757-4676

DOI: 10.15252/emmm.201809024

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.

Source: Scopus

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

Authors: de Kerckhove, M., Tanaka, K., Umehara, T., Okamoto, M., Kanematsu, S., Hayashi, H., Yano, H., Nishiura, S., Tooyama, S., Matsubayashi, Y., Komatsu, T., Park, S., Okada, Y., Takahashi, R., Kawano, Y., Hanawa, T., Iwasaki, K., Nozaki, T., Torigoe, H., Ikematsu, K., Suzuki, Y., Tanaka, K., Martin, P., Shimokawa, I., Mori, R.

Journal: EMBO Mol Med

Publication Date: 10/2018

Volume: 10

Issue: 10

eISSN: 1757-4684

DOI: 10.15252/emmm.201809024

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.

Source: PubMed

Targeting <i>miR-223</i> in neutrophils enhances theclearance of <i>Staphylococcus aureus</i> in infected wounds

Authors: de Kerckhove, M., Tanaka, K., Umehara, T., Okamoto, M., Kanematsu, S., Hayashi, H., Yano, H., Nishiura, S., Tooyama, S., Matsubayashi, Y., Komatsu, T., Park, S., Okada, Y., Takahashi, R., Kawano, Y., Hanawa, T., Iwasaki, K., Nozaki, T., Torigoe, H., Ikematsu, K., Suzuki, Y., Tanaka, K., Martin, P., Shimokawa, I., Mori, R.

Journal: EMBO MOLECULAR MEDICINE

Publication Date: 10/2018

Volume: 10

Issue: 10

eISSN: 1757-4684

ISSN: 1757-4676

DOI: 10.15252/emmm.201809024

Source: Web of Science

Targeting <i>miR-223</i> in neutrophils enhances the clearance of <i>Staphylococcus aureus</i> in infected wounds.

Authors: de Kerckhove, M., Tanaka, K., Umehara, T., Okamoto, M., Kanematsu, S., Hayashi, H., Yano, H., Nishiura, S., Tooyama, S., Matsubayashi, Y., Komatsu, T., Park, S., Okada, Y., Takahashi, R., Kawano, Y., Hanawa, T., Iwasaki, K., Nozaki, T., Torigoe, H., Ikematsu, K., Suzuki, Y., Tanaka, K., Martin, P., Shimokawa, I., Mori, R.

Journal: EMBO molecular medicine

Publication Date: 10/2018

Volume: 10

Issue: 10

Pages: e9024

eISSN: 1757-4684

ISSN: 1757-4676

DOI: 10.15252/emmm.201809024

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.

Source: Europe PubMed Central