Nanostructured, Self-Assembling Peptide K5 Blocks TNF-alpha and PGE(2) Production by Suppression of the AP-1/p38 Pathway

作者：Yang Woo Seok; Park Yung Chul; Kim Ji Hye; Kim Hye Ri; Yu Tao; Byeon Se Eun; Unsworth Larry D; Lee Jaehwi^*; Cho Jae Youl

来源：Mediators of Inflammation, 2012, 489810.

DOI：10.1155/2012/489810

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-) alpha and prostaglandin E-2 (PGE(2)) 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.

• 出版日期2012