Mitogen-activated protein kinases-dependent induction of hepatocyte growth factor production in human dermal fibroblasts by the antibiotic polymyxin B

Yoshihiro Sugiura, Kaori Hiramatsu, Reimi Hamauzu, Takahiro Motoki, Masahiro Miyazaki, Hirofumi Uto, Hirohito Tsubouchi, Satoshi Tanaka, Eiichi Gohda

Research output: Contribution to journalArticle

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Abstract

Hepatocyte growth factor (HGF) stimulates migration and proliferation of keratinocytes and has been suggested to be involved in wound healing. The cationic antibiotic polymyxin B (PMB) is commonly used as a topical antibiotic for wound care. If PMB possesses an HGF-inducing activity, the antibiotic is potentially beneficial for wound healing in addition to minimizing chances of infection. In this study, we found that PMB markedly induced HGF production from various types of cells including human dermal fibroblasts. Its effect was stronger than the effects of epidermal growth factor and cholera toxin and was comparable to the effect of 8-bromo-cAMP. Among the polymyxin family and polymyxin derivatives, colistin was also effective, whereas colistin methanesulfonate had only a marginal effect and PMB nonapeptide was ineffective. The stimulatory effect of PMB was accompanied by upregulation of HGF gene expression. Increase in phosphorylation of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) was observed from 0.25. h to 6. h after the addition of PMB, while increase in phosphorylation of p38 mitogen-activated protein kinase (MAPK) was detected from 24. h to 60. h after PMB addition. The MAPK/ERK kinase inhibitor PD98059, the JNK inhibitor SP600125 and the p38 MAPK inhibitor SB203580 all potently inhibited PMB-induced HGF production. Lastly, proliferation of human dermal fibroblasts was significantly stimulated by PMB. These results indicate that PMB-induced HGF production and proliferation of human dermal fibroblasts and suggest that activation of MAPKs is involved in the induction of HGF production.

Original languageEnglish
Pages (from-to)205-211
Number of pages7
JournalCytokine
Volume60
Issue number1
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Polymyxin B
Hepatocyte Growth Factor
Fibroblasts
Mitogen-Activated Protein Kinases
Anti-Bacterial Agents
Skin
Polymyxins
Colistin
Phosphorylation
JNK Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
Wound Healing
8-Bromo Cyclic Adenosine Monophosphate
Cholera Toxin
Mitogen-Activated Protein Kinase Kinases
Extracellular Signal-Regulated MAP Kinases
Protein Kinase Inhibitors
Keratinocytes
Epidermal Growth Factor
Gene expression

Keywords

  • Colistin
  • Extracellular signal-regulated kinase
  • Hepatocyte growth factor
  • Mitogen-activated protein kinase
  • Polymyxin b

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology
  • Biochemistry
  • Molecular Biology

Cite this

Mitogen-activated protein kinases-dependent induction of hepatocyte growth factor production in human dermal fibroblasts by the antibiotic polymyxin B. / Sugiura, Yoshihiro; Hiramatsu, Kaori; Hamauzu, Reimi; Motoki, Takahiro; Miyazaki, Masahiro; Uto, Hirofumi; Tsubouchi, Hirohito; Tanaka, Satoshi; Gohda, Eiichi.

In: Cytokine, Vol. 60, No. 1, 10.2012, p. 205-211.

Research output: Contribution to journalArticle

Sugiura, Y, Hiramatsu, K, Hamauzu, R, Motoki, T, Miyazaki, M, Uto, H, Tsubouchi, H, Tanaka, S & Gohda, E 2012, 'Mitogen-activated protein kinases-dependent induction of hepatocyte growth factor production in human dermal fibroblasts by the antibiotic polymyxin B', Cytokine, vol. 60, no. 1, pp. 205-211. https://doi.org/10.1016/j.cyto.2012.06.007
Sugiura, Yoshihiro ; Hiramatsu, Kaori ; Hamauzu, Reimi ; Motoki, Takahiro ; Miyazaki, Masahiro ; Uto, Hirofumi ; Tsubouchi, Hirohito ; Tanaka, Satoshi ; Gohda, Eiichi. / Mitogen-activated protein kinases-dependent induction of hepatocyte growth factor production in human dermal fibroblasts by the antibiotic polymyxin B. In: Cytokine. 2012 ; Vol. 60, No. 1. pp. 205-211.
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