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.

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.

• Authors: 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
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 70 Issue 2 Pg. 130-8 (May 2013) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 23433551 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antibodies, Anti-Idiotypic
• N-(3-oxododecanoyl)homoserine lactone
• Tumor Necrosis Factor-alpha
• Homoserine
• 4-Butyrolactone

Topics

• 4-Butyrolactone (analogs & derivatives, metabolism)
• Animals
• Antibodies, Anti-Idiotypic (pharmacology)
• Cell Proliferation
• Disease Models, Animal
• Epidermis (pathology)
• Homoserine (analogs & derivatives, metabolism)
• Male
• Neovascularization, Physiologic (physiology)
• Neutrophils (metabolism)
• Pseudomonas Infections (metabolism)
• Pseudomonas aeruginosa (metabolism)
• Rats
• Rats, Sprague-Dawley
• Tumor Necrosis Factor-alpha (drug effects, immunology, metabolism)
• Wound Healing (physiology)