RRC ID |
43926
|
著者 |
Sugiura Y, Hiramatsu K, Hamauzu R, Motoki T, Miyazaki M, Uto H, Tsubouchi H, Tanaka S, Gohda E.
|
タイトル |
Mitogen-activated protein kinases-dependent induction of hepatocyte growth factor production in human dermal fibroblasts by the antibiotic polymyxin B.
|
ジャーナル |
Cytokine
|
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 6h after the addition of PMB, while increase in phosphorylation of p38 mitogen-activated protein kinase (MAPK) was detected from 24h 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.
|
巻・号 |
60(1)
|
ページ |
205-11
|
公開日 |
2012-10-1
|
DOI |
10.1016/j.cyto.2012.06.007
|
PII |
S1043-4666(12)00252-9
|
PMID |
22749438
|
MeSH |
Anthracenes / pharmacology
Anti-Bacterial Agents / pharmacology
Blotting, Northern
Blotting, Western
Cell Line
Cell Line, Tumor
Cell Proliferation / drug effects
Cells, Cultured
Dermis / cytology
Dermis / drug effects
Dermis / metabolism
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Fibroblasts / drug effects*
Fibroblasts / metabolism
Flavonoids / pharmacology
Gene Expression Regulation / drug effects
Hepatocyte Growth Factor / genetics
Hepatocyte Growth Factor / metabolism*
Humans
Infant, Newborn
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
JNK Mitogen-Activated Protein Kinases / metabolism
Mitogen-Activated Protein Kinases / antagonists & inhibitors
Mitogen-Activated Protein Kinases / metabolism*
Phosphorylation / drug effects
Polymyxin B / pharmacology*
|
IF |
2.952
|
引用数 |
5
|
WOS 分野
|
IMMUNOLOGY
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
SK-N-SH(RCB0426) |