Neutrophil-derived tumor necrosis factor-α contributes to acute wound healing promoted by N-(3-oxododecanoyl)-l-homoserine lactone from Pseudomonas aeruginosa

Emi Kanno, Kazuyoshi Kawakami, Shinichi Miyairi, Hiromasa Tanno, Hirono Otomaru, Arina Hatanaka, Shiori Sato, Keiko Ishii, Denso Hayashi, Nobuhito Shibuya, Yoshimichi Imai, Naomasa Gotoh, Ryoko Maruyama, Masahiro Tachi

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Background: Pseudomonas aeruginosa is frequently isolated from chronic wounds and causes serious infection in immunocompromised hosts. N-(3-Oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL) is synthesized by an autoinducer synthase encoded by the bacterial lasI gene in P. aeruginosa, which regulates the production of virulence factors and biofilm formation in this bacterium. Recent studies have suggested that 3-oxo-C12-HSL contributes to the modulation of immune responses. However, the effect of this molecule on wound healing in P. aeruginosa infection remains to be elucidated. Objective: We used an animal model to study the effect of 3-oxo-C12-HSL on wound healing in skin infected with P. aeruginosa. Methods: Wounds were created on the backs of Sprague-Dawley (SD) rats and the P. aeruginosa strain PAO1 (PAO1) or its lasI deletion mutant (ΔlasI) was inoculated onto the wound surface. To examine the biological activity of 3-oxo-C12-HSL, rats were injected intraperitoneally with anti-3-oxo-C12-HSL antiserum or administered 3-oxo-C12-HSL at the wound surface. The wound tissues were harvested for analysis of the healing process and inflammatory response. Results: PAO1 inoculation significantly accelerated the wound healing and inflammatory response on day 3 post-wounding. These responses were reversed by inoculation with ΔlasI instead of PAO1 or treatment with anti-3-oxo-C12-HSL antiserum. In contrast, administration of 3-oxo-C12-HSL in the absence of PAO1 significantly promoted these responses, which were suppressed by the anti-TNF-α mAb. Conclusion: These results strongly suggest that 3-oxo-C12-HSL may be involved in healing wounds infected with P. aeruginosa through induction of inflammatory responses.

Original languageEnglish
Pages (from-to)130-138
Number of pages9
JournalJournal of dermatological science
Volume70
Issue number2
DOIs
Publication statusPublished - 2013 May

Keywords

  • N-(3-Oxododecanoyl)-l-homoserine lactone
  • Pseudomonas aeruginosa
  • Quorum sensing
  • TNF-α
  • Wound healing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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