TY - JOUR
T1 - Transgenic mice overexpressing PG1 display corneal opacity and severe inflammation in the eye
AU - Choi, Min Kyeung
AU - Le, Minh Thong
AU - Cho, Hye Sun
AU - Lee, Juyoung
AU - Jeon, Hyoim
AU - Cha, Se Yeoun
AU - Na, Manheum
AU - Chun, Taehoon
AU - Kim, Jin Hoi
AU - Song, Hyuk
AU - Park, Chankyu
N1 - Funding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (No. 2015R1A5A1009701), Republic of Korea.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/2
Y1 - 2021/2
N2 - Antimicrobial peptides (AMPs) are of interest as alternatives to antibiotics or immuno-modulators. 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.
AB - Antimicrobial peptides (AMPs) are of interest as alternatives to antibiotics or immuno-modulators. 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.
KW - Antimicrobial peptide
KW - Cathelicidin
KW - Corneal opacity
KW - Protegrin
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=85100333953&partnerID=8YFLogxK
U2 - 10.3390/ijms22041586
DO - 10.3390/ijms22041586
M3 - Article
C2 - 33557346
AN - SCOPUS:85100333953
VL - 22
SP - 1
EP - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 4
M1 - 1586
ER -