Nanostructured, self-assembling peptide K5 blocks TNF-α and PGE₂ production by suppression of the AP-1/p38 pathway.
Nanostructured, self-assembling peptides hold promise for a variety of regenerative medical applications such as 3D cell culture systems, accelerated wound healing, and nerve repair. The aim of this study was to determine whether the self-assembling peptide K5 can be applied as a carrier of anti-inflammatory drugs. First, we examined whether the K5 self-assembling peptide itself can modulate various cellular inflammatory responses. We found that peptide K5 significantly suppressed the release of tumor-necrosis-factor- (TNF-) α and prostaglandin E₂ (PGE₂) from RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Similarly, there was inhibition of cyclooxygenase- (COX-) 2 mRNA expression assessed by real-time PCR, indicating that the inhibition is at the transcriptional level. In agreement with this finding, peptide K5 suppressed the translocation of the transcription factors activator protein (AP-1) and c-Jun and inhibited upstream inflammatory effectors including mitogen activated protein kinase (MAPK), p38, and mitogen-activated protein kinase kinase 3/6 (MKK 3/6). Whether this peptide exerts its effects via a transmembrane or cytoplasmic receptor is not clear. However, our data strongly suggest that the nanostructured, self-assembling peptide K5 may possess significant anti-inflammatory activity via suppression of the p38/AP-1 pathway.
Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Woo Seok
WS
Yang
Yung Chul
YC
Park
Ji Hye
JH
Kim
Hye Ri
HR
Kim
Tao
T
Yu
Se Eun
SE
Byeon
Larry D
LD
Unsworth
Jaehwi
J
Lee
Jae Youl
JY
Cho
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis* / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
C083605:K5 peptide; D008070:Lipopolysaccharides; D010455:Peptides; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone