Protective and Anti-Inflammatory Effects of Protegrin-1 on <i>Citrobacter rodentium</i> Intestinal Infection in Mice
Infectious intestinal colitis, manifesting as intestinal inflammation, diarrhea, and epithelial barrier disruption, affects millions of humans worldwide and, without effective treatment, can result in death. In addition to this, the significant rise in antibiotic-resistant bacteria poses an urgent n...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/17/9494 |
| _version_ | 1797521339819491328 |
|---|---|
| author | Celina Osakowicz Lauren Fletcher Jeff L. Caswell Julang Li |
| author_facet | Celina Osakowicz Lauren Fletcher Jeff L. Caswell Julang Li |
| author_sort | Celina Osakowicz |
| collection | DOAJ |
| description | Infectious intestinal colitis, manifesting as intestinal inflammation, diarrhea, and epithelial barrier disruption, affects millions of humans worldwide and, without effective treatment, can result in death. In addition to this, the significant rise in antibiotic-resistant bacteria poses an urgent need for alternative anti-infection therapies for the treatment of intestinal disorders. Antimicrobial peptides (AMPs) are potential therapies that have broad-spectrum antimicrobial activity due to their (1) unique mode of action, (2) broad-spectrum antimicrobial activity, and (3) protective role in GI tract maintenance. Protegrin-1 (PG-1) is an AMP of pig origin that was previously shown to reduce the pathological effects of chemically induced digestive tract inflammation (colitis) and to modulate immune responses and tissue repair. This study aimed to extend these findings by investigating the protective effects of PG-1 on pathogen-induced colitis in an infection study over a 10-day experimental period. The oral administration of PG-1 reduced <i>Citrobacter rodentium</i> intestinal infection in mice as evidenced by reduced histopathologic change in the colon, prevention of body weight loss, milder clinical signs of disease, and more effective clearance of bacterial infection relative to challenged phosphate-buffered saline (PBS)-treated mice. Additionally, PG-1 treatment altered the expression of various inflammatory mediators during infection, which may act to resolve inflammation and re-establish intestinal homeostasis. PG-1 administered in its mature form was more effective relative to the pro-form (ProPG-1). To our knowledge, this is the first study demonstrating the protective effects of PG-1 on infectious colitis. |
| first_indexed | 2024-03-10T08:10:13Z |
| format | Article |
| id | doaj.art-df9eeac7b2344578b6f4494f080c3bfd |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:10:13Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-df9eeac7b2344578b6f4494f080c3bfd2023-11-22T10:44:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012217949410.3390/ijms22179494Protective and Anti-Inflammatory Effects of Protegrin-1 on <i>Citrobacter rodentium</i> Intestinal Infection in MiceCelina Osakowicz0Lauren Fletcher1Jeff L. Caswell2Julang Li3Department of Animal Biosciences, Ontario Agricultural College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Animal Biosciences, Ontario Agricultural College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Animal Biosciences, Ontario Agricultural College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Animal Biosciences, Ontario Agricultural College, University of Guelph, Guelph, ON N1G 2W1, CanadaInfectious intestinal colitis, manifesting as intestinal inflammation, diarrhea, and epithelial barrier disruption, affects millions of humans worldwide and, without effective treatment, can result in death. In addition to this, the significant rise in antibiotic-resistant bacteria poses an urgent need for alternative anti-infection therapies for the treatment of intestinal disorders. Antimicrobial peptides (AMPs) are potential therapies that have broad-spectrum antimicrobial activity due to their (1) unique mode of action, (2) broad-spectrum antimicrobial activity, and (3) protective role in GI tract maintenance. Protegrin-1 (PG-1) is an AMP of pig origin that was previously shown to reduce the pathological effects of chemically induced digestive tract inflammation (colitis) and to modulate immune responses and tissue repair. This study aimed to extend these findings by investigating the protective effects of PG-1 on pathogen-induced colitis in an infection study over a 10-day experimental period. The oral administration of PG-1 reduced <i>Citrobacter rodentium</i> intestinal infection in mice as evidenced by reduced histopathologic change in the colon, prevention of body weight loss, milder clinical signs of disease, and more effective clearance of bacterial infection relative to challenged phosphate-buffered saline (PBS)-treated mice. Additionally, PG-1 treatment altered the expression of various inflammatory mediators during infection, which may act to resolve inflammation and re-establish intestinal homeostasis. PG-1 administered in its mature form was more effective relative to the pro-form (ProPG-1). To our knowledge, this is the first study demonstrating the protective effects of PG-1 on infectious colitis.https://www.mdpi.com/1422-0067/22/17/9494antimicrobial peptideprotegrin-1immunomodulatory effect<i>Citrobacter rodentium</i> infectioninfectious colitis |
| spellingShingle | Celina Osakowicz Lauren Fletcher Jeff L. Caswell Julang Li Protective and Anti-Inflammatory Effects of Protegrin-1 on <i>Citrobacter rodentium</i> Intestinal Infection in Mice International Journal of Molecular Sciences antimicrobial peptide protegrin-1 immunomodulatory effect <i>Citrobacter rodentium</i> infection infectious colitis |
| title | Protective and Anti-Inflammatory Effects of Protegrin-1 on <i>Citrobacter rodentium</i> Intestinal Infection in Mice |
| title_full | Protective and Anti-Inflammatory Effects of Protegrin-1 on <i>Citrobacter rodentium</i> Intestinal Infection in Mice |
| title_fullStr | Protective and Anti-Inflammatory Effects of Protegrin-1 on <i>Citrobacter rodentium</i> Intestinal Infection in Mice |
| title_full_unstemmed | Protective and Anti-Inflammatory Effects of Protegrin-1 on <i>Citrobacter rodentium</i> Intestinal Infection in Mice |
| title_short | Protective and Anti-Inflammatory Effects of Protegrin-1 on <i>Citrobacter rodentium</i> Intestinal Infection in Mice |
| title_sort | protective and anti inflammatory effects of protegrin 1 on i citrobacter rodentium i intestinal infection in mice |
| topic | antimicrobial peptide protegrin-1 immunomodulatory effect <i>Citrobacter rodentium</i> infection infectious colitis |
| url | https://www.mdpi.com/1422-0067/22/17/9494 |
| work_keys_str_mv | AT celinaosakowicz protectiveandantiinflammatoryeffectsofprotegrin1onicitrobacterrodentiumiintestinalinfectioninmice AT laurenfletcher protectiveandantiinflammatoryeffectsofprotegrin1onicitrobacterrodentiumiintestinalinfectioninmice AT jefflcaswell protectiveandantiinflammatoryeffectsofprotegrin1onicitrobacterrodentiumiintestinalinfectioninmice AT julangli protectiveandantiinflammatoryeffectsofprotegrin1onicitrobacterrodentiumiintestinalinfectioninmice |