Protegrin, an antimicrobial peptide with therapeutic potential for colitis

Significance

Nowadays, several peptides seem promising for possible drug development. An example is cathelicidins, which are a class of antimicrobial peptides endogenously present in epithelial and immune cells with excellent antibacterial, antiviral, and antifungal activity. They have been widely studied for their antimicrobial functions in innate immune reactions during infection and inflammation. At sub-antimicrobial concentrations, different cathelicidins from various species have been shown to initiate chemotactic action on neutrophils, monocytes, dendritic cells, T-cells, and also to stimulate angiogenesis and wound healing. With regards to intestinal tissue repair, cathelicidins have been shown to have therapeutic potential for inflammatory bowel disease.

Despite the large amount of information about cathelicidins in mammals, there is still limited information on many peptide members in this class. For instance to fully understand the functional potential of pig cathelicidin, protegrin-1, we need to precisely understand their in vivo role. To this note, scientists at University of Guelph: Dr. Evanna Huynh, Dr. Jenna Penney, Professor Jeff Caswell and Professor Julang Li chose to look at the potential defensive functions of recombinant protegrin-1 (PG-1) in a mouse dextran sodium sulphate (DSS)- induced colitis inflammation model. This work is published in the peer review journal Frontiers in Pharmacology.

The authors used a DSS-induced mouse model where one group was induced with DSS alongside pro-, cathelin- or mature forms of protegrin (proPG + DSS, cathelin + DSS, and PG-1 + DSS, respectively) compared to mice administered DSS and buffer solution (PBS + DSS) or mice not administered DSS (PBS). In groups treated with DSS and protegrin, the body weight of the mice did not show any fundamental increment or decrease from Day 0 all through the experiment, while the body weight of the mice treated with DSS without protegrin (PBS + DSS) diminished significantly beginning from day 8 to the end of the trial. In addition, PG-1 treatments improved disease activity index and histological scores, suggesting a protective role of the antimicrobial peptide on colitis.

The University of Guelph researchers also revealed the molecular mechanism underlying the therapeutic effect of PG-1 and how the PG-1 changed the gene expression of inflammatory mediators and tissue repair factors including trefoil factor 3 (TFF3) and mucin (MUC-2). Moreover, detailed metabolic analysis showed reversal of the metabolite profile to normal in animals who took PG-1.

In a nutshell, Professor Julang Li and her colleagues successfully demonstrated that oral administration of the pro-form (proPG-1), the pro-region (cathelin-like area), and the mature PG-1 shielded the mice from developing DSS-induced colitis, suggesting a potential use for cathelicidin in treatment of intestinal inflammation. The study is the first report that compares the protective effects of recombinant PG-1 in its pro-, cathelin-, and mature form. Their study provides knowledge of a novel tissue protective role of protegrin, and may lead to the therapeutic potential of this antimicrobial peptide for inflammatory bowel disease. Such studies pave the way for potential application of PG-1 in treatment of various pathologies in human and animals.

Reference

Huynh, E., Penney, J., Caswell, J., Li, J. (2019), Protective Effects of Protegrin in Dextran Sodium Sulphate-Induced Murine Colitis, Front Pharmacol.2019 Feb 28;10:156.doi:10.3389/fphar.2019.00156.

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