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Transgenic Mice Overexpressing PG1 Display Corneal Opacity and Severe Inflammation in the Eye

Antimicrobial peptides (AMPs) are of interest as alternatives to antibiotics or immunomodulators. We generated and characterized the phenotypes of transgenic mice overexpressing protegrin 1 (PG1), a potent porcine cathelicidin. No obvious differences were observed between PG1 transgenic and wild-typ...

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Autores principales: Choi, Min-Kyeung, Le, Minh Thong, Cho, Hye-Sun, Lee, Juyoung, Jeon, Hyoim, Cha, Se-Yeoun, Na, Manheum, Chun, Taehoon, Kim, Jin-Hoi, Song, Hyuk, Park, Chankyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915784/
https://www.ncbi.nlm.nih.gov/pubmed/33557346
http://dx.doi.org/10.3390/ijms22041586
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author Choi, Min-Kyeung
Le, Minh Thong
Cho, Hye-Sun
Lee, Juyoung
Jeon, Hyoim
Cha, Se-Yeoun
Na, Manheum
Chun, Taehoon
Kim, Jin-Hoi
Song, Hyuk
Park, Chankyu
author_facet Choi, Min-Kyeung
Le, Minh Thong
Cho, Hye-Sun
Lee, Juyoung
Jeon, Hyoim
Cha, Se-Yeoun
Na, Manheum
Chun, Taehoon
Kim, Jin-Hoi
Song, Hyuk
Park, Chankyu
author_sort Choi, Min-Kyeung
collection PubMed
description Antimicrobial peptides (AMPs) are of interest as alternatives to antibiotics or immunomodulators. We generated and characterized the phenotypes of transgenic mice overexpressing protegrin 1 (PG1), a potent porcine cathelicidin. No obvious differences were observed between PG1 transgenic and wild-type mice in terms of growth, development, general behaviour, and the major immune cell population. However, PG1 transgenic mice intranasally infected with Staphylococcus aureus resulted in a reduction in microscopic pulmonary injury, improved clearance of bacteria, and lower proinflammatory cytokine secretion, compared to those of wild-type mice. On the other hand, approximately 25% of PG1 transgenic mice (n = 54/215) showed corneal opacity and developed inflammation in the eye, resulting ultimately in phthisis bulbi. Immunohistochemical analyses revealed that PG1 and its activator, neutrophil elastase, localized to the basal cells of the cornea and glands in eyelids, respectively. In addition, apoptosis indicated by a Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive signal was detected from flat cells of the cornea. Our study suggests that the expression regulation or localization of AMPs such as PG1 is important to prevent their adverse effects. However, our results also showed that the cytotoxic effects of PG1 on cells could be tolerated in animals, except for the eyes.
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spelling pubmed-79157842021-03-01 Transgenic Mice Overexpressing PG1 Display Corneal Opacity and Severe Inflammation in the Eye Choi, Min-Kyeung Le, Minh Thong Cho, Hye-Sun Lee, Juyoung Jeon, Hyoim Cha, Se-Yeoun Na, Manheum Chun, Taehoon Kim, Jin-Hoi Song, Hyuk Park, Chankyu Int J Mol Sci Article Antimicrobial peptides (AMPs) are of interest as alternatives to antibiotics or immunomodulators. We generated and characterized the phenotypes of transgenic mice overexpressing protegrin 1 (PG1), a potent porcine cathelicidin. No obvious differences were observed between PG1 transgenic and wild-type mice in terms of growth, development, general behaviour, and the major immune cell population. However, PG1 transgenic mice intranasally infected with Staphylococcus aureus resulted in a reduction in microscopic pulmonary injury, improved clearance of bacteria, and lower proinflammatory cytokine secretion, compared to those of wild-type mice. On the other hand, approximately 25% of PG1 transgenic mice (n = 54/215) showed corneal opacity and developed inflammation in the eye, resulting ultimately in phthisis bulbi. Immunohistochemical analyses revealed that PG1 and its activator, neutrophil elastase, localized to the basal cells of the cornea and glands in eyelids, respectively. In addition, apoptosis indicated by a Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive signal was detected from flat cells of the cornea. Our study suggests that the expression regulation or localization of AMPs such as PG1 is important to prevent their adverse effects. However, our results also showed that the cytotoxic effects of PG1 on cells could be tolerated in animals, except for the eyes. MDPI 2021-02-04 /pmc/articles/PMC7915784/ /pubmed/33557346 http://dx.doi.org/10.3390/ijms22041586 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Choi, Min-Kyeung
Le, Minh Thong
Cho, Hye-Sun
Lee, Juyoung
Jeon, Hyoim
Cha, Se-Yeoun
Na, Manheum
Chun, Taehoon
Kim, Jin-Hoi
Song, Hyuk
Park, Chankyu
Transgenic Mice Overexpressing PG1 Display Corneal Opacity and Severe Inflammation in the Eye
title Transgenic Mice Overexpressing PG1 Display Corneal Opacity and Severe Inflammation in the Eye
title_full Transgenic Mice Overexpressing PG1 Display Corneal Opacity and Severe Inflammation in the Eye
title_fullStr Transgenic Mice Overexpressing PG1 Display Corneal Opacity and Severe Inflammation in the Eye
title_full_unstemmed Transgenic Mice Overexpressing PG1 Display Corneal Opacity and Severe Inflammation in the Eye
title_short Transgenic Mice Overexpressing PG1 Display Corneal Opacity and Severe Inflammation in the Eye
title_sort transgenic mice overexpressing pg1 display corneal opacity and severe inflammation in the eye
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915784/
https://www.ncbi.nlm.nih.gov/pubmed/33557346
http://dx.doi.org/10.3390/ijms22041586
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