|Kim, Woo - Gyeongsang National University|
|Min, Wongi - Gyeongsang National University|
Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/2/2017
Publication Date: 3/2/2017
Publication URL: http://handle.nal.usda.gov/10113/5695443
Citation: Kim, W.H., Min, W., Lillehoj, H.S. 2017. Immunomodulatory activity of chicken NK-lysin peptides. Scientific Reports. 7: 45099.
Interpretive Summary: With the increasing emergence of antibiotic-resistant pathogens, there is a need to develop various alternative methods to control infectious diseases in order to decrease the use of drugs in animal agriculture. One of recent promising methods is to develop host-derived anti-microbial peptides (AMPs) which is less likely to develop drug resistance. In this report, ARS scientists investigated chicken AMP peptides which have shown to target pathogens as alternatives to antibiotics. Certain AMPs are highly conserved in all organisms and are cytotoxic against many bacteria, including multi-drug-resistant bacterial strains, by disrupting the bacterial membrane based on their cationic nature. Another property of AMPs involves the immunomodulation of host immune response. There is very little information on chicken AMPs that can modulate host immune system. In this study, the authors showed that chicken cell lines which have been treated with a chicken AMP protein secreted enhanced effector molecules that can activate molecular pathways to enhance host innate immunity. Although more studies will be needed to define the exact environmental conditions chicken AMP modulate host immunity, this information will be useful to understand how some AMP proteins can directly interact with host receptor proteins to enhance host defense mechanisms against diverse pathogens.
Technical Abstract: Chicken NK-lysin (cNK-lysin), the chicken homologue of human granulysin, is a cationic amphiphilic antimicrobial peptide (AMP) produced by cytotoxic T cells and natural killer cells. We have previously demonstrated that cNK-lysin and cNK-2, which is a synthetic peptide incorporating core alpha-helical region of cNK-lysin, have an antimicrobial activity against apicomplexan parasites, Eimeria spp. through its membrane disruptive property. Besides antimicrobial activity of AMP, the immunomodulatory activity through interaction with host cells is getting more attention recently. Thus, in this study we investigated if cNK-lysin derived peptides can modulate immune response in chicken macrophage cell line, HD11, and chicken primary monocytes in terms of induction of chemokines, anti-inflammatory property and activation of signaling pathway. cNK-2 induced expression of CCL4, CCL5 and interleukin-1ß (IL-1ß) in HD11 and CCL4 and CCL5 in primary monocytes, respectively. We also identified that cNK-2 suppressed lipopolysaccharide-induced inflammatory response by abrogation of IL-1ß expression. The immunomodulatory activity of cNK-2 involved mitogen-activated protein kinases mediated signaling pathway including p38, extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinases as well as internalization of cNK-2 into the cells. These results indicate that cNK-2 has potential as a novel immunomodulating agent rather than antimicrobial agent.