Evaluation of the Immunomodulatory Activity of the Chicken NK-Lysin-Derived Peptide cNK-2.
Chicken NK-lysin (cNK-lysin), the chicken homologue of human granulysin, is a cationic amphiphilic antimicrobial peptide (AMP) that is produced by cytotoxic T cells and natural killer cells. We previously demonstrated that cNK-lysin and cNK-2, a synthetic peptide incorporating the core α-helical region of cNK-lysin, have antimicrobial activity against apicomplexan parasites such as Eimeria spp., via membrane disruption. In addition to the antimicrobial activity of AMPs, the immunomodulatory activity of AMPs mediated by their interactions with host cells is increasingly recognized. Thus, in this study, we investigated whether cNK-lysin derived peptides modulate the immune response in the chicken macrophage cell line HD11 and in chicken primary monocytes by evaluating the induction of chemokines, anti-inflammatory properties, and activation of signalling pathways. cNK-2 induced the expression of CCL4, CCL5 and interleukin(IL)-1β in HD11 cells and CCL4 and CCL5 in primary monocytes. We also determined that cNK-2 suppresses the lipopolysaccharide-induced inflammatory response by abrogating IL-1β expression. The immunomodulatory activity of cNK-2 involves the mitogen-activated protein kinases-mediated signalling pathway, including p38, extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinases, as well as the internalization of cNK-2 into the cells. These results indicate that cNK-2 is a potential novel immunomodulating agent rather than an antimicrobial agent.
Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, ARS, U.S. Department of Agriculture, Beltsville, MD 20705, USA.
Woo H
WH
Kim
Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, ARS, U.S. Department of Agriculture, Beltsville, MD 20705, USA.
Hyun S
HS
Lillehoj
College of Veterinary Medicine &Institute of Animal Medicine, Gyeongsang National University, Jinju 52828, Korea.
Wongi
W
Min
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D002645:Chickens / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D020935:MAP Kinase Signaling System; D010455:Peptides / Q000494:pharmacology*; D011510:Proteolipids / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000900:Anti-Bacterial Agents; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; C093238:NK-lysin; D010455:Peptides; D011510:Proteolipids; C475945:peptide NK-2