Production and application of HMGB1 derived recombinant RAGE-antagonist peptide for anti-inflammatory therapy in acute lung injury
- Authors
- Lee, Seonyeong; Piao, Chunxian; Kim, Gyeungyun; Kim, Ji Yeon; Choi, Eunji; Lee, Minhyung
- Issue Date
- Mar-2018
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Anti-inflammation; Acute lung injury; Intratracheal administration; Receptor for advanced glycation end-products; Nuclear factor-kappa B; RAGE-antagonist peptide
- Citation
- EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, v.114, pp.275 - 284
- Indexed
- SCIE
SCOPUS
- Journal Title
- EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
- Volume
- 114
- Start Page
- 275
- End Page
- 284
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/4725
- DOI
- 10.1016/j.ejps.2017.12.019
- ISSN
- 0928-0987
- Abstract
- Acute lung injury (ALI) is an inflammatory lung disease caused by sepsis, infection, or ischemia-reperfusion. The receptor for advanced glycation end-products (RAGE) signaling pathway plays an important role in ALI. In this study, a novel RAGE-antagonist peptide (RAP) was produced as an inhibitor of the RAGE signaling pathway based on the RAGE-binding domain of high mobility group box-1 (HMGB1). Recombinant RAP was over-expressed and purified using nickel-affinity chromatography. In lipopolysaccharide-or HMGB1-activated RAW264.7 macrophage cells, RAP reduced the levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). RAP decreased the levels of cell surface RAGE and inhibited the nuclear translocation of nuclear factor-kappa B (NF-kappa B). These results imply that RAP decreases RAGE-mediated NF-kappa B activation and subsequent inflammatory reaction. For in vivo evaluation, RAP was delivered to the lungs of ALI-model animals via intratracheal administration. As a result, RAGE was down-regulated in the lung tissues by pulmonary delivery of RAP. Consequently, TNF-alpha, IL-6, and IL-1 beta were also reduced in broncoalveolar lavage fluid and the lung tissues of RAP-treated animals. Hematoxylin and eosin staining indicated that inflammation was decreased in RAP-treated animals. Collectively, these results suggest that RAP may be a useful treatment for ALI.
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