Targeted DNase treatment of obstructive lung disease: a pilot randomised controlled trial DOI Creative Commons
Netsanet A. Negewo, Natalie M. Niessen,

Penelope J. Baines

et al.

ERJ Open Research, Journal Year: 2024, Volume and Issue: 11(1), P. 00347 - 2024

Published: Oct. 10, 2024

Sputum extracellular DNA (eDNA) is associated with disease severity in asthma and COPD therefore emerging as a potential therapeutic target. The aim of this study was to investigate the effect 10 days recombinant human DNase (rhDNase) treatment eDNA-high on sputum eDNA levels, neutrophil-related inflammation, lung function symptoms. Adults (n=80) or (n=66) were screened for presence high (>20 µg·mL-1) those eligible (n=18 asthma, n=17 COPD) randomised two-period crossover controlled trial consisting daily nebulised rhDNase (2.5 mg/2.5 mL) placebo (5 mL 0.9% saline) days, 2-week washout period. primary outcome eDNA, secondary outcomes included neutrophil trap (NET)-related biomarkers, inflammatory cell counts, respiratory At screening, significantly higher total count, colour score inflammation (HNP1-3, LL-37 interleukin-1β) both compared low groups. In participants older had poorer control eDNA. Administration reduced levels (median (Q1-Q3) Pre: 48.4 (22.1-74.1); Post: 17.0 (5.0-31.0) µg·mL-1; p=0.022) 39.3 (36.7-55.6); 25.4 (11.3-38.6) p=0.044) placebo. Symptoms, NET biomarkers remained unchanged. there reduction banded blood neutrophils (3.2 (0-7.7) 0.0 (0.0-1.5); p=0.044). Targeted effectively COPD.

Language: Английский

Interleukin‐8/Matrix Metalloproteinase‐9 Axis Impairs Wound Healing in Type 2 Diabetes through Neutrophil Extracellular Traps‐Fibroblast Crosstalk DOI Creative Commons
Dimitrios Tsilingiris,

Anastasia‐Maria Natsi,

Efstratios Gavriilidis

et al.

European Journal of Immunology, Journal Year: 2025, Volume and Issue: 55(4)

Published: April 1, 2025

Neutrophils interact with and activate fibroblasts through the release of neutrophil extracellular traps (NETs). We investigated role NETs-fibroblast crosstalk in cutaneous wound healing type 2 diabetes (T2D). Neutrophils/NETs, serum, primary human skin (HSFs) were obtained from individuals T2D age/sex-matched controls. NET-stimulation studies performed on neutrophils/HSFs, without specific inhibitors, while HSF capacity was assessed using a scratch assay. HSFs display profibrotic phenotype, showing increased CCN2/CTGF, α-smooth muscle actin, collagen release, albeit impaired capacity, elevated I C-terminal telopeptide, degradation associated (∼3.5-fold) matrix metalloproteinase-9 (MMP-9) neutrophils/NETs. IL-8 induced expression MMP-9 Moreover, neutrophils/NETs exhibited content, which acted an autocrine/paracrine fashion to further augment its production by neutrophils/HSFs. The findings validated normoglycemic during hyperglycemic clamp concomitant lipid infusion corroborated immunohistochemically diabetic plantar ulcer biopsies. This novel, vicious circle NETs/interleukin-8/MMP-9/HSFs hindered or blockade via inhibitors dismantling NET-scaffold DNase I, suggesting candidate therapeutic targets impairment T2D.

Language: Английский

Citations

0

A causal effects of neutrophil extracellular traps and its biomarkers on acute respiratory distress syndrome: a two-sample Mendelian randomization study DOI Creative Commons
Yuqing Chen, Ruolin Mao, Qing Chang

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 8, 2025

Language: Английский

Citations

0

Mycobacterium tuberculosis in a Trap: The Role of Neutrophil Extracellular Traps in Tuberculosis DOI Open Access
Luiz Henrique Agra Cavalcante‐Silva, Fernanda Silva Almeida, Arthur Gomes de Andrade

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11385 - 11385

Published: July 13, 2023

Mycobacterium tuberculosis complex causes (TB), a disease that pulmonary inflammation but can also affect other tissues. Despite macrophages having defined role in TB immunopathogenesis, innate immune cells, such as neutrophils, are involved this process. These cells have high phagocytic ability and microbial-killing machine comprised of enzymes, antimicrobial peptides, reactive oxygen species. In the last two decades, new neutrophil response, extracellular traps (NETs), has been intensely researched. NETs comprise DNA associated with histones, peptides. structures related to response some immuno-pathogenesis mechanisms. This mini review highlights how they be helpful diagnostic tool and/or therapeutic target.

Language: Английский

Citations

9

Modulation of Unregulated Inflammation‐Associated Coagulopathy in Sepsis Using Multifunctional Nanosheets DOI

Yongqiang Xiao,

Fang He, Xin Wang

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(38)

Published: May 2, 2024

Abstract Excessive inflammation‐associated unregulated coagulation leads to disseminated intravascular (DIC) and mortality in patients with sepsis worldwide, current clinical treatment is unsatisfactory. Recent studies have shown that circulating cell‐free DNA (cfDNA) neutrophil extracellular traps (NETs), act as potent pro‐inflammation pro‐coagulation agents, revealing a mechanistic link between innate immunity coagulation. After establishing definite correlation cfDNA dysfunctional inflammation disorders samples from sepsis, novel 2D, sheet‐like, cationic scavenger using polyamidoamine (P‐G1) antimicrobial peptides (AMPs) covered black phosphorus (BP) nanosheets, called BP‐G1 AMP, are fabricated. It found AMP significantly suppressed bacterial growth ameliorated the systemic inflammatory response, associated disorder, DIC, resulting improved survival cecal ligation puncture (CLP) mouse model. This study proposes strategy for fabricating multifunctional nanosheets can ameliorate during treatment. These findings demonstrate importance of 2D nanostructures construction multivalent anti‐bacterial anti‐coagulation nanoplatforms.

Language: Английский

Citations

3

Functional immunophenotyping of blood neutrophils identifies novel endotypes of viral response in preschool children with recurrent wheezing DOI Creative Commons
Anne M. Fitzpatrick,

Ahmad F. Mohammad,

Min Huang

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2023, Volume and Issue: 152(6), P. 1433 - 1443

Published: Aug. 19, 2023

Language: Английский

Citations

8

Navigating the terrain of neutrophil extracellular traps in severe malaria pathogenesis DOI
Maria Saeed, Elizabeth H. Aitken, Stephen J. Rogerson

et al.

Trends in Parasitology, Journal Year: 2024, Volume and Issue: 40(4), P. 278 - 279

Published: March 13, 2024

Language: Английский

Citations

1

Guardians Turned Culprits: NETosis and Its Influence on Pulmonary Fibrosis Development DOI

Aleena Varughese,

Akarsha Balnadupete,

Poornima Ramesh

et al.

Molecular Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: May 8, 2024

Language: Английский

Citations

1

The role and mechanism of extracellular traps in chronic rhinosinusitis DOI Open Access
Jiani Li, He Zhao, Jing Yang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 181, P. 117655 - 117655

Published: Nov. 1, 2024

Language: Английский

Citations

1

Unripe Rubus occidentalis, Ellagic Acid, and Urolithin A Attenuate Inflammatory Responses in IL-1β-Stimulated A549 Cells and PMA-Stimulated Differentiated HL-60 Cells DOI Creative Commons
Soo‐Jin Kim, Jiyeon Kim, Youngcheon Song

et al.

Nutrients, Journal Year: 2023, Volume and Issue: 15(15), P. 3364 - 3364

Published: July 28, 2023

Unripe Rubus occidentalis (uRO) contains various natural polyphenols with beneficial physiological activities and is particularly rich in ellagic acid (EA). EA has ameliorated type 2 inflammation airway hyperresponsiveness animal models of eosinophilic asthma. metabolized by the gut microbiota to urolithin A (UA), which exhibits anti-inflammatory properties. However, it remains unclear whether uRO, EA, UA reduce inflammatory responses oxidative stress respiratory epithelial cells neutrophils. In this study, was induced A549 (human lung cells) dHL-60 (neutrophil-like differentiated from human promyelocytic leukemia HL-60 treated concentrations water extract uRO (uRO-w), UA. uRO-w suppressed cytokine chemokine levels reduced expression matrix metalloproteinase-9 stimulated IL-1β. As a result analyzing mechanism these molecules are expressed, found that uRO-w, regulated corticosteroid-sensitive mitogen activated protein kinase, nuclear factor κB, corticosteroid-insensitive AKT. addition, significantly reactive oxygen species phorbol 12-myristate 13-acetate-stimulated inhibited neutrophil extracellular trap formation. Therefore, our results suggest potential therapeutic agents for preventing treating diseases.

Language: Английский

Citations

2

Acute rhinosinusitis: treatment with a focus on key elements of pathogenesis DOI

E.V. Nosulya,

И.А. Ким,

Yu.V. Luchsheva

et al.

Russian Rhinology, Journal Year: 2023, Volume and Issue: 31(3), P. 212 - 212

Published: Jan. 1, 2023

Language: Английский

Citations

2