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-inf...

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Main Authors: Woo Seok Yang, Yung Chul Park, Ji Hye Kim, Hye Ri Kim, Tao Yu, Se Eun Byeon, Larry D. Unsworth, Jaehwi Lee, Jae Youl Cho
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2012/489810
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author Woo Seok Yang
Yung Chul Park
Ji Hye Kim
Hye Ri Kim
Tao Yu
Se Eun Byeon
Larry D. Unsworth
Jaehwi Lee
Jae Youl Cho
author_facet Woo Seok Yang
Yung Chul Park
Ji Hye Kim
Hye Ri Kim
Tao Yu
Se Eun Byeon
Larry D. Unsworth
Jaehwi Lee
Jae Youl Cho
author_sort Woo Seok Yang
collection DOAJ
description 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.
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spelling doaj-art-c95c8f1f858d450db685a730c7426edb2025-02-03T01:00:54ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/489810489810Nanostructured, Self-Assembling Peptide K5 Blocks TNF-α and PGE2 Production by Suppression of the AP-1/p38 PathwayWoo Seok Yang0Yung Chul Park1Ji Hye Kim2Hye Ri Kim3Tao Yu4Se Eun Byeon5Larry D. Unsworth6Jaehwi Lee7Jae Youl Cho8Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaCollege of Forest & Environmental Sciences, Kangwon National University, Chuncheon 200-701, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaCollege of Forest & Environmental Sciences, Kangwon National University, Chuncheon 200-701, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaDepartment of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, T6G 2G6, CanadaCollege of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaNanostructured, 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.http://dx.doi.org/10.1155/2012/489810
spellingShingle Woo Seok Yang
Yung Chul Park
Ji Hye Kim
Hye Ri Kim
Tao Yu
Se Eun Byeon
Larry D. Unsworth
Jaehwi Lee
Jae Youl Cho
Nanostructured, Self-Assembling Peptide K5 Blocks TNF-α and PGE2 Production by Suppression of the AP-1/p38 Pathway
Mediators of Inflammation
title Nanostructured, Self-Assembling Peptide K5 Blocks TNF-α and PGE2 Production by Suppression of the AP-1/p38 Pathway
title_full Nanostructured, Self-Assembling Peptide K5 Blocks TNF-α and PGE2 Production by Suppression of the AP-1/p38 Pathway
title_fullStr Nanostructured, Self-Assembling Peptide K5 Blocks TNF-α and PGE2 Production by Suppression of the AP-1/p38 Pathway
title_full_unstemmed Nanostructured, Self-Assembling Peptide K5 Blocks TNF-α and PGE2 Production by Suppression of the AP-1/p38 Pathway
title_short Nanostructured, Self-Assembling Peptide K5 Blocks TNF-α and PGE2 Production by Suppression of the AP-1/p38 Pathway
title_sort nanostructured self assembling peptide k5 blocks tnf α and pge2 production by suppression of the ap 1 p38 pathway
url http://dx.doi.org/10.1155/2012/489810
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