Topical Administration of Heat-Killed <i>Enterococcus faecalis</i> Strain KH2 Promotes Re-Epithelialization and Granulation Tissue Formation during Skin Wound-Healing
Hiromasa Tanno,
Emi Kanno,
Shiho Kurosaka,
Yukari Oikawa,
Takumi Watanabe,
Ko Sato,
Jun Kasamatsu,
Tomomitsu Miyasaka,
Shinyo Ishi,
Miki Shoji,
Naoyuki Takagi,
Yoshimichi Imai,
Keiko Ishii,
Masahiro Tachi,
Kazuyoshi Kawakami
Affiliations
Hiromasa Tanno
Department of Science of Nursing Practice, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Emi Kanno
Department of Science of Nursing Practice, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Shiho Kurosaka
Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Yukari Oikawa
Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Takumi Watanabe
Bio-Lab Co., Ltd., 2-1-3 Komagawa, Hidaka-shi 350-1249, Japan
Ko Sato
Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Jun Kasamatsu
Department of Intelligent Network for Infection Control, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Tomomitsu Miyasaka
Division of Pathophysiology, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan
Shinyo Ishi
Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Miki Shoji
Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Naoyuki Takagi
Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Yoshimichi Imai
Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Keiko Ishii
Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Masahiro Tachi
Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Kazuyoshi Kawakami
Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Lactic acid bacteria (LAB) are known to have beneficial effects on immune responses when they are orally administered as bacterial products. Although the beneficial effects of LAB have been reported for the genera Lactobacillus and Lactococcus, little has been uncovered on the effects of the genus Enterococcus on skin wound-healing. In this study, we aimed to clarify the effect of heat-killed Enterococcus faecalis KH2 (heat-killed KH2) strain on the wound-healing process and to evaluate the therapeutic potential in chronic skin wounds. We analyzed percent wound closure, re-epithelialization, and granulation area, and cytokine and growth factor production. We found that heat-killed KH2 contributed to the acceleration of re-epithelialization and the formation of granulation tissue by inducing tumor necrosis factor-α, interleukin-6, basic fibroblast growth factor, transforming growth factor (TGF)-β1, and vascular endothelial growth factor production. In addition, heat-killed KH2 also improved wound closure, which was accompanied by the increased production of TGF-β1 in diabetic mice. Topical administration of heat-killed KH2 might have therapeutic potential for the treatment of chronic skin wounds in diabetes mellitus. In the present study, we concluded that heat-killed KH2 promoted skin wound-healing through the formation of granulation tissues and the production of inflammatory cytokines and growth factors.
