scholarly journals Adjunctive Thymosin Beta-4 Treatment Influences MΦ Effector Cell Function to Improve Disease Outcome in Pseudomonas aeruginosa-Induced Keratitis

2021 ◽  
Vol 22 (20) ◽  
pp. 11016
Author(s):  
Yuxin Wang ◽  
Thomas W. Carion ◽  
Abdul Shukkur Ebrahim ◽  
Gabriel Sosne ◽  
Elizabeth A. Berger
Keyword(s):  
Wound Healing ◽  
Reactive Nitrogen Species ◽  
Cell Function ◽  
In Vitro Studies ◽  
Raw 264.7 Cells ◽  
Reactive Nitrogen ◽  
Nitrogen Species ◽  
Bacterial Killing ◽  
Thymosin Beta 4

Our previous work has shown that topical thymosin beta 4 (Tβ4) as an adjunct to ciprofloxacin treatment reduces inflammatory mediators and inflammatory cell infiltrates (neutrophils/PMN and macrophages/MΦ) while enhancing bacterial killing and wound healing pathway activation in an experimental model of P. aeruginosa-induced keratitis. This study aimed to mechanistically examine how Tβ4 influences MΦ function in particular, leading to reduced inflammation and enhanced host defense following P. aeruginosa-induced infection of the cornea. Flow cytometry was conducted to profile the phenotype of infiltrating MΦ after infection, while generation of reactive nitrogen species and markers of efferocytosis were detected to assess functional activity. In vitro studies were performed utilizing RAW 264.7 cells to verify and extend the in vivo findings. Tβ4 treatment decreases MΦ infiltration and regulates the activation state in response to infected corneas. MΦ functional data demonstrated that the adjunctive Tβ4 treatment group significantly downregulated reactive nitrogen species (RNS) production and efferocytotic activity. In addition, the in vitro studies showed that both Tβ4 alone and adjunctive Tβ4 treatment influenced MΦ cellular function following LPS stimulation. Collectively, these data provide further evidence that adjunctive Tβ4 + ciprofloxacin treatment offers a more efficacious option for treating bacterial keratitis. Not only does the adjunctive therapy address both the infectious pathogen and corneal wound healing response, but it also influences MΦ infiltration, activation, and function, as revealed by the current study.

Inhibition of Reactive Nitrogen Species in Vitro and ex Vivo by Trypsin Inhibitor from Sweet Potato ‘Tainong 57' Storage Roots

2007 ◽  
Vol 55 (15) ◽  
pp. 6000-6006 ◽  
Author(s):  
Guan-Jhong Huang ◽  
Ming-Jyh Sheu ◽  
Hsien-Jung Chen ◽  
Yuan-Shiun Chang ◽  
Yaw-Huei Lin
Keyword(s):  
Sweet Potato ◽  
Trypsin Inhibitor ◽  
Reactive Nitrogen Species ◽  
Ex Vivo ◽  
Reactive Nitrogen ◽  
Nitrogen Species ◽  
Storage Roots

scholarly journals Myeloperoxidase-generated reactive nitrogen species convert LDL into an atherogenic form in vitro

1999 ◽  
Vol 103 (11) ◽  
pp. 1547-1560 ◽  
Author(s):  
Eugene A. Podrez ◽  
David Schmitt ◽  
Henry F. Hoff ◽  
Stanley L. Hazen
Keyword(s):  
Reactive Nitrogen Species ◽  
Reactive Nitrogen ◽  
Nitrogen Species

scholarly journals On the Liquid Chemistry of the Reactive Nitrogen Species Peroxynitrite and Nitrogen Dioxide Generated by Physical Plasmas

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1687
Author(s):  
Giuliana Bruno ◽  
Sebastian Wenske ◽  
Jan-Wilm Lackmann ◽  
Michael Lalk ◽  
Thomas von Woedtke ◽  
...  
Keyword(s):  
Reactive Nitrogen Species ◽  
High Resolution Mass Spectrometry ◽  
Clinical Effectiveness ◽  
Covalent Modification ◽  
Reactive Nitrogen ◽  
Nitrogen Species ◽  
Plasma Parameters ◽  
Cold Plasmas ◽  
Major Application

Cold physical plasmas modulate cellular redox signaling processes, leading to the evolution of a number of clinical applications in recent years. They are a source of small reactive species, including reactive nitrogen species (RNS). Wound healing is a major application and, as its physiology involves RNS signaling, a correlation between clinical effectiveness and the activity of plasma-derived RNS seems evident. To investigate the type and reactivity of plasma-derived RNS in aqueous systems, a model with tyrosine as a tracer was utilized. By high-resolution mass spectrometry, 26 different tyrosine derivatives including the physiologic nitrotyrosine were identified. The product pattern was distinctive in terms of plasma parameters, especially gas phase composition. By scavenger experiments and isotopic labelling, gaseous nitric dioxide radicals and liquid phase peroxynitrite ions were determined as dominant RNS. The presence of water molecules in the active plasma favored the generation of peroxynitrite. A pilot study, identifying RNS driven post-translational modifications of proteins in healing human wounds after the treatment with cold plasma (kINPen), demonstrated the presence of in vitro determined chemical pathways. The plasma-driven nitration and nitrosylation of tyrosine allows the conclusion that covalent modification of biomolecules by RNS contributes to the clinically observed impact of cold plasmas.

scholarly journals Host-derived Reactive Nitrogen Species mediate the Cryptococcus neoformans yeast-to-titan switch via fungal-derived superoxide

2021 ◽  
Author(s):  
Xin Zhou ◽  
Guillaume E. Desanti ◽  
Robin C May ◽  
Ivy M Dambuza ◽  
Elizabeth R Ballou
Keyword(s):  
Cryptococcus Neoformans ◽  
Reactive Nitrogen Species ◽  
Molecular Mechanisms ◽  
Protein A ◽  
Genotoxic Stress ◽  
Strand Break ◽  
Reactive Nitrogen ◽  
Nitrogen Species ◽  
Sod Activity

In the host lung, the human fungal pathogen Cryptococcus neoformans undergoes a morphological switch from small haploid yeast to large polyploid titan cell, contributing to C. neoformans virulence. Titan cells are less readily phagocytosed and can survive host nitrosative and oxidative stresses. We and others previously showed that titanization is triggered by host-relevant signals including CO2 and lung-resident bacteria, and addition of these factor is sufficient to induce titan cells in vitro. Here we investigate the molecular mechanisms that drive this transition and demonstrate that host-derived immune signals can increase the degree and frequency of titanization. Specifically, host-relevant reactive nitrogen species increase the accumulation of endogenous superoxide within cryptococcal cells, particularly within nuclei, where it can cause genotoxic stress. Consistent with this, we observe the accumulation of Rad51 protein, a marker of the double strand break repair pathway, in titanizing cultures. Blocking superoxide accumulation inhibits titanization, yet titanization also requires superoxide detoxification through Superoxide Dismutase (SOD) activity. Loss of mitochondrial Sod2 activity locks cells in the yeast phase, while Sod1 is required for the production of viable titan daughter cells. We hypothesize that the redox responsive transcription factor Yap1 in part mediates this response by regulating SOD2/SOD1. In addition, we show that Sod1 translocates to the nucleus, where it is likely involved in the detoxification of genotoxic superoxide. Together, these findings reveal a major new regulatory mechanism for the yeast-to-titan transition.

Reactive Nitrogen Species Modulate the Effects of Rhein, an Active Component of Senna Laxatives, on Human Epithelium In Vitro

2002 ◽  
Vol 34 (5) ◽  
pp. 529-534 ◽  
Author(s):  
Francesco Raimondi ◽  
Pasquale Santoro ◽  
Luigi Maiuri ◽  
Marco Londei ◽  
Simona Annunziata ◽  
...  
Keyword(s):  
Reactive Nitrogen Species ◽  
Active Component ◽  
Reactive Nitrogen ◽  
Nitrogen Species

Inhibition of reactive nitrogen species in vitro and ex vivo by thioredoxin h2 from sweet potato ‘Tainong 57’ storage roots

2012 ◽  
Vol 131 (2) ◽  
pp. 552-557 ◽  
Author(s):  
Guan-Jhong Huang ◽  
Jeng-Shyan Deng ◽  
Hsien-Jung Chen ◽  
Shyh-Shyun Huang ◽  
Chieh-Hsi Wu ◽  
...  
Keyword(s):  
Sweet Potato ◽  
Reactive Nitrogen Species ◽  
Ex Vivo ◽  
Reactive Nitrogen ◽  
Nitrogen Species ◽  
Storage Roots

scholarly journals Adjunctive Thymosin Beta-4 Treatment Influences PMN Effector Cell Function during Pseudomonas aeruginosa-Induced Corneal Infection

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3579
Author(s):  
Yuxin Wang ◽  
Thomas W. Carion ◽  
Abdul Shukkur Ebrahim ◽  
Gabriel Sosne ◽  
Elizabeth A. Berger
Keyword(s):  
Effector Cell ◽  
Cell Function ◽  
Natural Extension ◽  
Bacterial Killing ◽  
Disease Response ◽  
Functional Studies ◽  
Thymosin Beta 4 ◽  
Well Data

Previous work examining the therapeutic efficacy of adjunct thymosin beta 4 (Tβ4) to ciprofloxacin for ocular infectious disease has revealed markedly reduced inflammation (inflammatory mediators and innate immune cells) with increased activation of wound healing pathways. Understanding the therapeutic mechanisms of action have further revealed a synergistic effect with ciprofloxacin to enhance bacterial killing along with a regulatory influence over macrophage effector cell function. As a natural extension of the aforementioned work, the current study uses an experimental model of P. aeruginosa-induced keratitis to examine the influence of Tβ4 regarding polymorphonuclear leukocyte (PMN/neutrophil) cellular function, contributing to improved disease response. Flow cytometry was utilized to phenotypically profile infiltrating PMNs after infection. The generation of reactive oxygen species (ROS), neutrophil extracellular traps (NETs), and PMN apoptosis were investigated to assess the functional activities of PMNs in response to Tβ4 therapy. In vitro work using peritoneal-derived PMNs was similarly carried out to verify and extend our in vivo findings. The results indicate that the numbers of infiltrated PMNs into infected corneas were significantly reduced with adjunctive Tβ4 treatment. This was paired with the downregulated expression of proinflammatory markers on these cells, as well. Data generated from PMN functional studies suggested that the corneas of adjunctive Tβ4 treated B6 mice exhibit a well-regulated production of ROS, NETs, and limited PMN apoptosis. In addition to confirming the in vivo results, the in vitro findings also demonstrated that neutrophil elastase (NE) was unnecessary for NETosis. Collectively, these data provide additional evidence that adjunctive Tβ4 + ciprofloxacin treatment is a promising option for bacterial keratitis that addresses both the infectious pathogen and cellular-mediated immune response, as revealed by the current study.

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