Neutrophil defensin 4

The pathogenesis of psoriasis can be explained by dysregulation of immunological cell function as well as keratinocyte proliferation/differentiation. Recently, the immunological pathomechanism has been clarified substantially. Whereas T-helper (Th)1 overactivation was thought to induce occurrence of psoriasis, it has been demonstrated that Th17 cells play a key role. Th17 development is maintained by interleukin (IL)-23 mainly produced by dendritic cells. Th17 cells produce various cytokines, including IL-17A, IL-17F and IL-22. IL-17A and IL-22 induce not only keratinocyte proliferation, but also tumor necrosis factor (TNF)-α, chemokine (C-X-C motif) ligand (CXCL)1 and CXCL8 production. TNF-α accelerates the infiltration of inflammatory cells, including lymphocytes, monocytes and neutrophils, from the peripheral blood into skin with dendritic cell activation. In addition, antimicrobial peptides are overexpressed in psoriatic skin lesions, and the antimicrobial peptide, LL-37, activates dendritic cells, which leads to the development of inflammation. Furthermore, activation of nuclear factor-κB signal induces the expression of keratins 6 and 16 in keratinocytes, which are associated with acanthosis and reduced turnover time in the epidermis. The progression of the pathomechanism contributes to the development of new therapies for psoriasis.

The occurrence and spread of multidrug-resistant bacteria is a prominent health concern. To curb this urgent threat, new innovative strategies pursuing novel antimicrobial agents are of the utmost importance. Here, we unleashed the antimicrobial activity of human neutrophil peptide-4 (HNP-4) by tryptic digestion. We identified a single 11 amino acid long fragment (HNP-41 - 11) with remarkable antimicrobial potential, exceeding that of the full length peptide on both mass and molar levels. Importantly, HNP-41 - 11 was equally bactericidal against multidrug-resistant and non-resistant strains; a potency that was further enhanced by N- and C-terminus modifications (acetylation and amidation, respectively). These observations, combined with negligible cytotoxicity not exceeding that of the full length peptide, presents proteolytic digestion of innate host-defense-peptides as a novel strategy to overcome the current health crisis related to antibiotic-resistant bacteria.

Background: Adenoviruses are highly contagious pathogens which cause respiratory disease particularly in children; they may induce severe disease in infants. Human neutrophil peptides (HNPs) have been found to exhibit antiadenoviral activity. Thus, we have investigated HNPs in nasal aspirates (NAs) of children suffering from adenoviral common cold. Objective: To investigate the release of HNP-1-4 in adenovirus infection and the relationship with self-limiting upper respiratory tract infections. Methods: Nasal aspirate samples (n=14) were obtained from children (aged 6-12 years) infected with adenovirus between June 2012 and December 2015. Control samples were taken 4 weeks after infection when the children were asymptomatic. Levels of HNPs were measured using an enzyme-linked immunosorbent assay (ELISA). Results: There were increased levels of HNP-1, -3, and -4, but not HNP-2, in nasal aspirates (NAs) during adenovirus infections compared to healthy specimens (p ≤ 0.01). Moreover, there was also increase in the neutrophil count, which is a known cell source of HNPs. Conclusion: Our finding supports the involvement of HNP-1, -3, and -4 in naturally occurring cold in children infected with adenovirus. Because of their known antiviral properties, it is tempting to hypothesize that HNPs might play a protective role in adenovirus-induced respiratory disease; however, this remains to be shown.