Abstract
Inflammation is the body's response to injury or infection and is important for healing and eliminating pathogens; however, prolonged inflammation is damaging and may lead to the development of chronic inflammatory disorders. Recently, there has been interest in exploiting antimicrobial peptides (AMPs) that exhibit immunoregulatory activities to treat inflammatory diseases. In this study, we investigated the immunomodulatory effects of lactoferrin-derived lactoferricin AMPs from three different species (bovine, mouse, and human) with subtle differences in their amino acid sequences that alter their antimicrobial action; to our knowledge, no other studies have compared their immunomodulatory effects. Macrophages, key players in the induction and propagation of inflammation, were used to investigate the effects of species-specific lactoferricin peptides on inflammatory processes. Bovine lactoferricin was the only one of the three peptides studied that downregulated lipopolysaccharide (LPS)-induced pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6, in both human and mouse macrophages. Lactoferricin regulated inflammation through targeting LPS-activated nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling pathways. Although the immunoregulatory role of lactoferricin during an inflammatory response in vivo is yet to be elucidated, further investigation with the use of animal models is warranted by the current findings. The ability of lactoferricin, especially that of bovine origin, to downregulate macrophage-mediated inflammatory responses suggests potential for the development of this peptide as a novel immunotherapeutic agent in the treatment of chronic inflammatory conditions.
Highlights
Inflammation is the body’s innate response to invading pathogens or tissue trauma
This is consistent with other studies of antimicrobial peptides (AMPs) and their immunomodulatory effects on a variety of different cells that employed peptide concentrations ranging from 1-30 μM [23,24,25,26,27,28]
The ability of bovine, mouse and human lactoferricin peptides to downregulate pro-inflammatory cytokine mRNA expression by LPS-stimulated macrophages was investigated in a series of quantitative real-time polymerase chain reaction (q-PCR) experiments
Summary
One of the immune system’s most prevalent cytokine producers detect stress signals or pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides (LPS) during the early onset of infection and release a variety of proinflammatory mediators that include tumor-necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and nitric oxide (NO) [1]. This further promotes the recruitment and activation of leukocytes via signaling pathways including the nuclear factor-kappa B (NF-κB) pathway and the mitogen-activated protein kinase (MAPK) pathway [2,3,4]. Conclusions: The ability of lactoferricin, especially that of bovine origin, to downregulate macrophage-mediated inflammatory responses suggests potential for the development of this peptide as a novel immunotherapeutic agent in the treatment of chronic inflammatory conditions
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