Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity

Jue Yeon Lee,1,* Jin Sook Suh,2,* Jung Min Kim,1 Jeong Hwa Kim,1 Hyun Jung Park,1 Yoon Jeong Park,1,2 Chong Pyoung Chung1 1Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Chungcheongbuk-do, Republic of Korea; 2Dental Regenerative Biotechnology, Dental Resear...

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Autores principales:	Lee JY, Suh JS, Kim JM, Kim JH, Park HJ, Park YJ, Chung CP
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/22c1ec115eaa48319539af2d9f59ac7b
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spelling	oai:doaj.org-article:22c1ec115eaa48319539af2d9f59ac7b2021-12-02T00:10:22ZIdentification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity1178-2013https://doaj.org/article/22c1ec115eaa48319539af2d9f59ac7b2015-08-01T00:00:00Zhttp://www.dovepress.com/identification-of-a-cell-penetrating-peptide-domain-from-human-beta-de-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jue Yeon Lee,1,* Jin Sook Suh,2,* Jung Min Kim,1 Jeong Hwa Kim,1 Hyun Jung Park,1 Yoon Jeong Park,1,2 Chong Pyoung Chung1 1Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Chungcheongbuk-do, Republic of Korea; 2Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: Human beta-defensins (hBDs) are crucial factors of intrinsic immunity that function in the immunologic response to a variety of invading enveloped viruses, bacteria, and fungi. hBDs can cause membrane depolarization and cell lysis due to their highly cationic nature. These molecules participate in antimicrobial defenses and the control of adaptive and innate immunity in every mammalian species and are produced by various cell types. The C-terminal 15-mer peptide within hBD3, designated as hBD3-3, was selected for study due to its cell- and skin-penetrating activity, which can induce anti-inflammatory activity in lipopolysaccharide-treated RAW 264.7 macrophages. hBD3-3 penetrated both the outer membrane of the cells and mouse skin within a short treatment period. Two other peptide fragments showed poorer penetration activity compared to hBD3-3. hBD3-3 inhibited the lipopolysaccharide-induced production of inducible nitric oxide synthase, nitric oxide, and secretory cytokines, such as interleukin-6 and tumor necrosis factor in a concentration-dependent manner. Moreover, hBD3-3 reduced the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. Further investigation also revealed that hBD3-3 downregulated nuclear factor kappa B-dependent inflammation by directly suppressing the degradation of phosphorylated-IκBα and by downregulating active nuclear factor kappa B p65. Our findings indicate that hBD3-3 may be conjugated with drugs of interest to ensure their proper translocation to sites, such as the cytoplasm or nucleus, as hBD3-3 has the ability to be used as a carrier, and suggest a potential approach to effectively treat inflammatory diseases. Keywords: human beta-defensin 3, cell-penetrating peptide, anti-inflammatory activity, lipopolysaccharide, NF-κB canonical pathwayLee JYSuh JSKim JMKim JHPark HJPark YJChung CPDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 5423-5434 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Lee JY Suh JS Kim JM Kim JH Park HJ Park YJ Chung CP Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity
description	Jue Yeon Lee,1,* Jin Sook Suh,2,* Jung Min Kim,1 Jeong Hwa Kim,1 Hyun Jung Park,1 Yoon Jeong Park,1,2 Chong Pyoung Chung1 1Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Chungcheongbuk-do, Republic of Korea; 2Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: Human beta-defensins (hBDs) are crucial factors of intrinsic immunity that function in the immunologic response to a variety of invading enveloped viruses, bacteria, and fungi. hBDs can cause membrane depolarization and cell lysis due to their highly cationic nature. These molecules participate in antimicrobial defenses and the control of adaptive and innate immunity in every mammalian species and are produced by various cell types. The C-terminal 15-mer peptide within hBD3, designated as hBD3-3, was selected for study due to its cell- and skin-penetrating activity, which can induce anti-inflammatory activity in lipopolysaccharide-treated RAW 264.7 macrophages. hBD3-3 penetrated both the outer membrane of the cells and mouse skin within a short treatment period. Two other peptide fragments showed poorer penetration activity compared to hBD3-3. hBD3-3 inhibited the lipopolysaccharide-induced production of inducible nitric oxide synthase, nitric oxide, and secretory cytokines, such as interleukin-6 and tumor necrosis factor in a concentration-dependent manner. Moreover, hBD3-3 reduced the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. Further investigation also revealed that hBD3-3 downregulated nuclear factor kappa B-dependent inflammation by directly suppressing the degradation of phosphorylated-IκBα and by downregulating active nuclear factor kappa B p65. Our findings indicate that hBD3-3 may be conjugated with drugs of interest to ensure their proper translocation to sites, such as the cytoplasm or nucleus, as hBD3-3 has the ability to be used as a carrier, and suggest a potential approach to effectively treat inflammatory diseases. Keywords: human beta-defensin 3, cell-penetrating peptide, anti-inflammatory activity, lipopolysaccharide, NF-κB canonical pathway
format	article
author	Lee JY Suh JS Kim JM Kim JH Park HJ Park YJ Chung CP
author_facet	Lee JY Suh JS Kim JM Kim JH Park HJ Park YJ Chung CP
author_sort	Lee JY
title	Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity
title_short	Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity
title_full	Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity
title_fullStr	Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity
title_full_unstemmed	Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity
title_sort	identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/22c1ec115eaa48319539af2d9f59ac7b
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Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity

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