Abstract
Cathelicidins, a class of antimicrobial peptides, have been widely studied for their antimicrobial role in innate immune responses during infection and inflammation. At sub-antimicrobial concentrations, various cathelicidins from different species have been reported to exert chemotactic activity on neutrophils, monocytes, dendritic cells and T-cells, and also enhance angiogenesis and wound healing. To date, the role of the pig cathelicidin, protegrin-1 (PG-1), in immune modulation and tissue repair in the intestinal tract has not been investigated. The aim of the present study was to examine the potential protective effects of recombinant PG-1 in a mouse dextran sodium sulfate (DSS)-induced colitis inflammation model. This is the first report showing the protective effects of PG-1 in its various forms (pro-, cathelin-, and mature-forms) in attenuating significant body weight loss associated with DSS-induced colitis (p < 0.05). PG-1 treatment improved histological scores (P < 0.05) and influenced the gene expression of inflammatory mediators and tissue repair factors such as trefoil factor 3 (TFF3) and mucin (MUC-2). Protegrin treatment also altered the metabolite profile, returning the metabolite levels closer to untreated control levels. These findings lay the foundation for future oral application of recombinant PG-1 to potentially treat intestinal damage and inflammation.
Highlights
Inflammatory bowel disease (IBD) is characterized by inflammation of the intestinal tract that can lead to decreased epithelial barrier function
We examined the effects of proform PG-1 (ProPG), the cathelin domain, and mature-form PG-1 produced by P. pastoris in a mouse model of dextran sodium sulfate (DSS)-induced colitis
Significant weight loss from initial (Day 0) body weight (BW) was evident in the PBS + DSS group when compared to the healthy negative control, administered PBS (Figure 2A), suggesting that DSS effectively induced colitis
Summary
Inflammatory bowel disease (IBD) is characterized by inflammation of the intestinal tract that can lead to decreased epithelial barrier function. Cathelicidin is a class of antimicrobial peptides (AMPs) endogenously present in epithelial and immune cells with potent antibacterial, antiviral, and antifungal functions (Bals, 2000). It is certain that neutrophil granules contain sufficiently high concentrations of AMPs to cause direct antimicrobial activity (Ganz, 1987). At sites such as mucosal surfaces, it is unclear whether direct antimicrobial activity of AMPs occurs, as they may be abrogated by serum and divalent cations when produced and secreted at lower concentrations by epithelial cells (Ganz, 2003; Bowdish et al, 2006). Cathelicidins have been shown to enhance angiogenesis and wound healing (Zanetti, 2005; Wuerth and Hancock, 2011; Yeung et al, 2011)
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