title: Neutrophil-derived tumor necrosis factor-α contributes to acute wound healing promoted by N-(3-oxododecanoyl)-L-homoserine lactone from Pseudomonas aeruginosa.
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.
  
  
  CONCLUSIONS
  These results strongly suggest that 3-oxo-C12-HSL may be involved in healing wounds infected with P. aeruginosa through induction of inflammatory responses.
authors: Department of Science of Nursing Practice, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan. ekanno@med.tohoku.ac.jp
authors: Emi
authors: E
authors: Kanno
authors: Kazuyoshi
authors: K
authors: Kawakami
authors: Shinichi
authors: S
authors: Miyairi
authors: Hiromasa
authors: H
authors: Tanno
authors: Hirono
authors: H
authors: Otomaru
authors: Arina
authors: A
authors: Hatanaka
authors: Shiori
authors: S
authors: Sato
authors: Keiko
authors: K
authors: Ishii
authors: Denso
authors: D
authors: Hayashi
authors: Nobuhito
authors: N
authors: Shibuya
authors: Yoshimichi
authors: Y
authors: Imai
authors: Naomasa
authors: N
authors: Gotoh
authors: Ryoko
authors: R
authors: Maruyama
authors: Masahiro
authors: M
authors: Tachi
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004817:Epidermis / Q000473:pathology; D006714:Homoserine / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; C109860:N-(3-oxododecanoyl)homoserine lactone; D014409:Tumor Necrosis Factor-alpha; D006714:Homoserine; D015107:4-Butyrolactone