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Published on: January 5, 2017
Porcine-derived antimicrobial peptide PR39 alleviates DSS-induced colitis via the NF-κB/MAPK pathway
Xinyun Qin1, Zhineng Liu1, Keyi Nong1
1School of Tropical Agriculture and Forestry, Hainan University, Haikou 570228, China.
Abstract:
PR39 is an antimicrobial peptide (AMP) with a variety of biological functions, including antimicrobial, wound healing, leukocyte chemotaxis, angiogenesis, and immunomodulation; however, its therapeutic efficacy in colitis (IBD) has rarely been reported. For this reason, the present study aimed to investigate the therapeutic effect of PR39 on IBD and its underlying mechanisms. In this experiment, a mouse model of ulcerative colitis (UC) was induced with 3 % dextran sulfate (DSS) and administered by rectal injection of PR39. The results of the study showed that 5 mg/kg of PR39 was able to ameliorate the clinical manifestations of DSS-induced UC mice by improving the clinical symptoms, colonic tissue damage, up-regulating the expression of tight junction proteins, and alleviating the systemic inflammation in mice in various ways. The mechanism of action may involve inhibition of the phosphorylation level of proteins related to the NF-κB/MAPK signaling pathway and modulation of the relative abundance of potentially pathogenic (Bacteroides, Pseudoflavonifractor, Barnesiella, and Oscillibacter) and potentially beneficial bacteria (Candidatus_Saccharibacteria, Desulfovibrio, Saccharibacteria) in the intestinal flora. The results enriched the biological functions of PR-39 and also suggested that PR-39 may be able to be used as a novel drug for the treatment of IBD.
Insights
PR39, an antimicrobial peptide, shows therapeutic potential for treating inflammatory bowel disease (IBD). This study demonstrates PR39 ameliorates ulcerative colitis (UC) in mice by reducing inflammation and improving gut barrier function.
Area of Science:
- Biochemistry
- Immunology
- Microbiology
Background:
- Antimicrobial peptides (AMPs) like PR39 possess diverse biological activities.
- Therapeutic applications of PR39 in inflammatory bowel disease (IBD), specifically ulcerative colitis (UC), remain largely unexplored.
Purpose of the Study:
- To investigate the therapeutic efficacy of PR39 in a mouse model of DSS-induced UC.
- To elucidate the underlying mechanisms of PR39's action in UC.
Main Methods:
- Induction of UC in mice using 3% dextran sulfate (DSS).
- Rectal administration of PR39 to DSS-treated mice.
- Assessment of clinical symptoms, colonic tissue damage, tight junction protein expression, and systemic inflammation.
- Analysis of NF-κB/MAPK signaling pathway phosphorylation and gut microbiota composition.
Main Results:
- PR39 (5 mg/kg) significantly improved clinical symptoms and reduced colonic tissue damage in UC mice.
- PR39 treatment upregulated tight junction proteins and alleviated systemic inflammation.
- Mechanisms involved inhibition of NF-κB/MAPK signaling and modulation of gut microbiota.
Conclusions:
- PR39 demonstrates significant therapeutic effects in a DSS-induced UC mouse model.
- PR39's mechanism involves regulating inflammatory signaling pathways and gut microbial balance.
- PR39 represents a potential novel therapeutic agent for IBD treatment.
