Hindawi Publishing Corporation Mediators of Inflammation Volume 2012, Article ID 489810, 8 pages doi:10.1155/2012/489810 Research Article Nanostructured, Self-Assembling Peptide K5 Blocks TNF-α and PGE 2 Production by Suppression of the AP-1/p38 Pathway Woo Seok Yang, 1 Yung Chul Park, 2 Ji Hye Kim, 1 Hye Ri Kim, 2 Tao Yu, 1 Se Eun Byeon, 1 Larry D. Unsworth, 3 Jaehwi Lee, 4 and Jae Youl Cho 1 1 Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea 2 College of Forest & Environmental Sciences, Kangwon National University, Chuncheon 200-701, Republic of Korea 3 Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, Canada T6G 2G6 4 College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea Correspondence should be addressed to Jaehwi Lee, jaehwi@cau.ac.kr and Jae Youl Cho, jaecho@skku.edu Received 19 September 2011; Accepted 17 November 2011 Academic Editor: Fulvio D’Acquisto Copyright © 2012 Woo Seok Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 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. 1. Introduction Inflammation is one of the body innate immune responses and is mainly mediated by macrophages. When viruses or bacteria infect the body, significant cooperation among macrophages, dendritic cells, B cells, and T cells is required. Various inflammatory molecules, such as cytokines (e.g., tumor-necrosis-factor- (TNF-) α), chemokines, and medi- ators (including nitric oxide (NO) and prostaglandin E 2 (PGE 2 )), are known to play critical roles in managing crosstalk between immune cells in both acute and chronic responses [1, 2]. In this regard, the initial activation of macrophages in inflammatory events could be an important step. Initiation of the macrophage inflammatory process is triggered by the activation of receptors such as Toll-like receptor (TLR) 4 and TLR3 through the binding of their lig- ands, such as lipopolysaccharide (LPS) and poly(I:C), respec- tively [3]. A series of intracellular signaling events follows, managed by the activities of nonreceptor protein tyrosine kinases and mitogen-activated protein kinases (MAPKs), including ERK (extracellular signal-related kinase), p38, and JNK (C-Jun N-terminal kinase), as well as the activation and upregulation of transcription factors (e.g., nuclear-factor- (NF-) κB and activator-protein- (AP) 1) [4, 5]. Eventually, these responses lead macrophages to be transcriptionally activated to express proinflammatory genes encoding such