Production of proteolytic enzymes in mast cells, fibroblasts, vascular smooth muscle and endothelial cells cultivated under normoxic or hypoxic conditions

Maxová, Hana; Bačáková, Lucie; Vaccari, Lisa; Novotná, Jana; Tomášová, H; Vízek, M; Herget, J

doi:10.33549/physiolres.931909

Cited by 15 publications

(1 citation statement)

References 37 publications

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“…Overexpression of P2X7R leads to an increase in tumour growth, metastasis, production of VEGF, and release of matrix metalloproteinases (MMPs) [ 65 ], which are proteolytic enzymes that degrade extracellular matrix proteins and play a key role in metastasis [ 47 ]. Tumours expressing P2X7R are also characterised by increased proliferation, decreased apoptosis, and high levels of the transcription factor nuclear factor of activated T cells 1 (NFATc1).…”

Section: The Role Of P2x7 Receptor In Cancermentioning

confidence: 99%

The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications

Rotondo

Mazziotta

Lanzillotti

et al. 2022

Cancers

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The purinergic P2X7 receptor (P2X7R) is a transmembrane protein whose expression has been related to a variety of cellular processes, while its dysregulation has been linked to inflammation and cancer. P2X7R is expressed in cancer and immune system cell surfaces. ATP plays a key role in numerous metabolic processes due to its abundance in the tumour microenvironment. P2X7R plays an important role in cancer by interacting with ATP. The unusual property of P2X7R is that stimulation with low doses of ATP causes the opening of a permeable channel for sodium, potassium, and calcium ions, whereas sustained stimulation with high doses of ATP favours the formation of a non-selective pore. The latter effect induces a change in intracellular homeostasis that leads to cell death. This evidence suggests that P2X7R has both pro- and anti-tumour proprieties. P2X7R is increasingly recognised as a regulator of inflammation. In this review, we aimed to describe the most relevant characteristics of P2X7R function, activation, and its ligands, while also summarising the role of P2X7R activation in the context of inflammation and cancer. The currently used therapeutic approaches and clinical trials of P2X7R modulators are also described.

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Section: The Role Of P2x7 Receptor In Cancermentioning

confidence: 99%

The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications

Rotondo

Mazziotta

Lanzillotti

et al. 2022

Cancers

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Searching for tryptase in the RBL‐2H3 mast cell model: Preparation for comparative mast cell toxicology studies with zebrafish

Shim

Kennedy

Weatherly

et al. 2018

J of Applied Toxicology

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Mast cells comprise a physiologically and toxicologically important cell type that is ubiquitous among species and tissues. Mast cells undergo degranulation, in which characteristic intracellular granules fuse with the plasma membrane and release many bioactive substances, such as enzymes β‐hexosaminidase and tryptase. Activity of mast cells in the toxicology model organism, zebrafish, has been monitored via tryptase release and cleavage of substrate N‐α‐benzoyl‐dl‐Arg‐p‐nitroanilide (BAPNA). An extensively used in vitro mast cell model for studying toxicant mechanisms is the RBL‐2H3 cell line. However, instead of tryptase, granule contents such as β‐hexosaminidase have usually been employed as RBL‐2H3 degranulation markers. To align RBL‐2H3 cell toxicological studies to in vivo mast cell studies using zebrafish, we aimed to develop an RBL‐2H3 tryptase assay. Unexpectedly, we discovered that tryptase release from RBL‐2H3 cells is not detectable, using BAPNA substrate, despite optimized assay that can detect as little as 1 ng tryptase. Additional studies performed with another substrate, tosyl‐Gly‐Pro‐Lys‐pNA, and with an enzyme‐linked immunosorbent assay, revealed a lack of tryptase protein released from stimulated RBL‐2H3 cells. Furthermore, none of the eight rat tryptase genes (Tpsb2, Tpsab1, Tpsg1, Prss34, Gzmk, Gzma, Prss29, Prss41) is expressed in RBL‐2H3 cells, even though all are found in RBL‐2H3 genomic DNA and even though β‐hexosaminidase mRNA is constitutively expressed. Therefore, mast cell researchers should utilize β‐hexosaminidase or another reliable marker for RBL‐2H3 degranulation studies, not tryptase. Comparative toxicity testing in RBL‐2H3 cells in vitro and in zebrafish mast cells in vivo will require use of a degranulation reporter different from tryptase.

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Prolonged Treatment with Inhaled Corticosteroids does not Normalize High Activity of Matrix Metalloproteinase-9 in Exhaled Breath Condensates of Children with Asthma

Grzela

Zagórska

Krejner

et al. 2015

Arch. Immunol. Ther. Exp.

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The airway remodeling in asthma is associated with increased amount of matrix metalloproteinase (MMP)-9. High levels of MMP-9 were found in mucosal biopsies, sputum and in exhaled breath condensates (EBC) of asthma patients. However, there are no data concerning real in vivo activity. Inhaled corticosteroids are effective in asthma control, but it is unclear, whether they only attenuate inflammation, or also protect against progressive remodeling of respiratory tract. Therefore, the aim of the study was to assess the amount and activity of MMP-9 in context of pro-inflammatory cytokines (IL-6, IL-8 and tumor necrosis factor, TNF), measured in EBC of asthma-suffering children, treated with inhaled steroids. The study involved 27 children with asthma, continuously treated with inhaled fluticasone propionate, and 22 healthy controls. In addition to routine clinical screening, the selected cytokines in EBC were analyzed using Ultrasensitive ELISA, whereas activity of MMP-9 was assessed using a novel immunozymography method. Despite chronic treatment with inhaled steroids mean MMP-9/EBC activity in asthma group was significantly higher than in healthy controls. Moreover, high MMP-9/EBC in asthma-suffering children significantly correlated with IgE serum levels. The IL-6 and IL-8 concentration was below the detection limit in all EBC samples. TNF/EBC levels were similar in both, asthma and healthy children. We hypothesize that MMP-9 hyperactivity in asthma may be closely related to high IgE serum levels. Our results suggest that inhaled steroids may be ineffective to prevent asthma-associated airway remodeling. Finally, we emphasize the necessity of further research focused on MMP-9 inhibition in asthma treatment.

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Production of proteolytic enzymes in mast cells, fibroblasts, vascular smooth muscle and endothelial cells cultivated under normoxic or hypoxic conditions

Cited by 15 publications

References 37 publications

The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications

The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications

Searching for tryptase in the RBL‐2H3 mast cell model: Preparation for comparative mast cell toxicology studies with zebrafish

Prolonged Treatment with Inhaled Corticosteroids does not Normalize High Activity of Matrix Metalloproteinase-9 in Exhaled Breath Condensates of Children with Asthma

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