Human neutrophil peptide 1 promotes immune sterilization in vivo by reducing the virulence of multidrug‐resistant <i>Klebsiella pneumoniae</i> and increasing the ability of macrophages

Wang, Huiyun; Chen, Xiaochun; Yan, Zhihan; Tu, Fan; He, Tian Tian; Gopinath, Subash C. B.; Rui, Xiaohong; Cao, Fu-tao

doi:10.1002/bab.2270

Cited by 5 publications

(4 citation statements)

References 43 publications

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“…This aspect needs to be confirmed in prospective trials in order to evaluate whether HNP adds information within the multifactorial risk profile for BPD. The role of HNPs in the immune defense is currently under discussion (2,28), so our data may add new information to this topic.…”

Section: Discussionmentioning

confidence: 85%

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Lactoferrin and Human Neutrophil Protein (HNP) 1–3 Levels During the Neonatal Period in Preterm Infants

et al. 2022

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Antimicrobial polypeptides (APPs) are part of the innate immune system, but their specific role in the context of preterm birth is not yet understood. The aim of this investigation was to determine the systemic expression of APPs, i.e., lactoferrin (LF) and human neutrophil protein (HNP) 1–3 in preterm infants in the period of highest vulnerability for infection and to correlate these biomarkers with short-term outcome. We therefore conducted a prospective two-center study including plasma samples of 278 preterm infants and 78 corresponding mothers. APP levels were analyzed on day 1, 3, 7, and 21 of life via enzyme-linked immunosorbent assay (ELISA). The levels of LF and HNP1–3 remained stable during the first 21 days of life and were not influenced by maternal levels. Elevated APP levels were found at day 1 in infants born to mothers with amniotic infection syndrome (AIS vs. no AIS, mean ± SD in ng/ml: LF 199.8 ± 300 vs. 124.1 ± 216.8, HNP 1–3 16,819 ± 36,124 vs. 8,701 ± 11,840; p = 0.021, n = 179). We found no elevated levels of APPs before the onset of sepsis episodes or in association with other short-term outcomes that are in part mediated by inflammation such as necrotizing enterocolitis (NEC) or retinopathy of prematurity (ROP). Interestingly, infants developing bronchopulmonary dysplasia (BPD) showed higher levels of HNP1–3 on day 21 than infants without BPD (13,473 ± 16,135 vs. 8,388 ± 15,938, n = 111, p = 0.008). In infants born without amniotic infection, levels of the measured APPs correlated with gestational age and birth weight. In our longitudinal study, systemic levels of LF and HNP 1–3 were not associated with postnatal infection and adverse short-term outcomes in preterm infants.

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Section: Discussionmentioning

confidence: 85%

“…Antimicrobial polypeptides (APPs), a large group of proteins with pleiotropic functions, are part of the innate immune system and have direct antimicrobial capacity ( 2 , 3 ). APPs may also modulate immune defense pathways ( 4 ) and inflammatory processes ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Lactoferrin and Human Neutrophil Protein (HNP) 1–3 Levels During the Neonatal Period in Preterm Infants

et al. 2022

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“…Previous studies of NP-1 have mainly focused on inflammatory-immune disease research. And NP-1 has been shown to promote immune sterilization in vivo by increasing the ability of macrophages [ 31 ] . The results published by Rivas-Santiago and Soldati, et al, who demonstrated that NP-1 was lowered in elderly people [32] and smokers [33] , are consistent with our observation that NP-1 was decreased in cardiac remodeling and hypertrophic cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

NP-1 Reverses Left Ventricular Remodeling in Hypertension through Inhibiting NF-KB Signaling Pathway

duan

Zhou

Si³

et al. 2022

Preprint

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BACKGROUND Reversing hypertensive ventricular remodeling could reduce cardiovascular disease, but it’s reversal rate is low. Neutrophil Peptide 1 ( NP-1 ) is under intensive investigation as a potential therapeutic agent. But it’s role in hypertensive ventricular remodeling remains unclear. METHODS We collected data from hypertensive patients and measured NP-1 levels using an ELISA. We established hypertensive ventricular remodeling models and then treated with NP-1 or BAY 11-7082, an inhibitor of NF-кB. The cardiac hypertrophy markers and NF-кB factors were detected through HE, Masson, IHC, qPCR, and WB. We also established hypertrophic cardiomyocyte models and then dealt with NP-1 or BAY 11-7082. The myocardial hypertrophy indicators and NF-кB factors were measured by IF, qPCR, and WB. RESULTS We found the NP-1 level was decreased in patients with hypertensive ventricular remodeling. It’s demonstrated that NP-1 expression was decreased in hypertensive ventricular remodeling models. While NP-1 treatment has the potential to raise NP-1 levels and reverse ventricular remodeling. It’s also noticed a decrease with NP-1 in hypertrophic cardiomyocyte models. NP-1 disposal could improve NP-1 expression and reverse cardiomyocyte hypertrophy. Besides, our study found the activation of NF-кB in animal and cell models. And it could be inhibited by dealing with NP-1, which was similar to an inhibitor of NF-кB. CONCLUSIONS NP-1 could reverse ventricular remodeling and cardiomyocyte hypertrophy through inhibiting the activation of NF-кB. This may serve as a potential therapeutic target for cardiovascular disease.

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“…Additionally, in LPS-primed macrophages, HNP-1 can promote pyroptosis and increase IL-1β release through inflammasome activation via the P2X7 receptor [ 78 ]. HNP-1 was reported to increase oxidative stress and autophagy-related genes, and with this enhanced endocytosis more antigens could be processed and presented [ 79 ]. Through the P2Y6 receptor signaling pathway, HNP-1 suppresses neutrophil apoptosis, prolonging their lifespan [ 80 ].…”

Section: Immune-related Functions Relevant In the Tumor Microenvironmentmentioning

confidence: 99%

Role of Defensins in Tumor Biology

Adyns

Proost

Struyf

2023

IJMS

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Defensins have long been considered as merely antimicrobial peptides. Throughout the years, more immune-related functions have been discovered for both the α-defensin and β-defensin subfamily. This review provides insights into the role of defensins in tumor immunity. Since defensins are present and differentially expressed in certain cancer types, researchers started to unravel their role in the tumor microenvironment. The human neutrophil peptides have been demonstrated to be directly oncolytic by permealizing the cell membrane. Further, defensins can inflict DNA damage and induce apoptosis of tumor cells. In the tumor microenvironment, defensins can act as chemoattractants for subsets of immune cells, such as T cells, immature dendritic cells, monocytes and mast cells. Additionally, by activating the targeted leukocytes, defensins generate pro-inflammatory signals. Moreover, immuno-adjuvant effects have been reported in a variety of models. Therefore, the action of defensins reaches beyond their direct antimicrobial effect, i.e., the lysis of microbes invading the mucosal surfaces. By causing an increase in pro-inflammatory signaling events, cell lysis (generating antigens) and attraction and activation of antigen presenting cells, defensins could have a relevant role in activating the adaptive immune system and generating anti-tumor immunity, and could thus contribute to the success of immune therapy.

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Human neutrophil peptide 1 promotes immune sterilization in vivo by reducing the virulence of multidrug‐resistant Klebsiella pneumoniae and increasing the ability of macrophages

Cited by 5 publications

References 43 publications

Lactoferrin and Human Neutrophil Protein (HNP) 1–3 Levels During the Neonatal Period in Preterm Infants

Lactoferrin and Human Neutrophil Protein (HNP) 1–3 Levels During the Neonatal Period in Preterm Infants

NP-1 Reverses Left Ventricular Remodeling in Hypertension through Inhibiting NF-KB Signaling Pathway

Role of Defensins in Tumor Biology

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