Protective and Anti-Inflammatory Effects of Protegrin-1 on Citrobacter rodentium Intestinal Infection in Mice.

Abstract

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 Citrobacter rodentium 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.

• Authors: Celina Osakowicz, Lauren Fletcher, Jeff L Caswell, Julang Li
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 17 (Aug 31 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34502403 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Antimicrobial Cationic Peptides
• Cytokines
• Pore Forming Cytotoxic Proteins
• protegrin-1

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antimicrobial Cationic Peptides (metabolism, pharmacology)
• Citrobacter rodentium (drug effects)
• Colitis (pathology)
• Colon (pathology)
• Cytokines (metabolism)
• Disease Models, Animal
• Enterobacteriaceae Infections (drug therapy)
• Female
• Inflammation
• Intestinal Mucosa (drug effects, metabolism)
• Intestines (drug effects)
• Mice
• Mice, Inbred C57BL
• Pore Forming Cytotoxic Proteins (pharmacology)