Publications

Authors:

Schioppa, Tiziana; Nguyen, Hoang Oanh; Salvi, Valentina; Maugeri, Norma; Facchinetti, Fabrizio; Villetti, Gino; Civelli, Maurizio; Gaudenzi, Carolina; Passari, Mauro; Sozio, Francesca; Barbazza, Ilaria; Tamassia, Nicola; Cassatella, Marco A; Del Prete, Annalisa; Bosisio, Daniela; Tiberio, Laura

Title:

The PDE4 Inhibitor Tanimilast Restrains the Tissue-Damaging Properties of Human Neutrophils

Year:

2022

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ISSN of journal:

1422-0067

N° Volume:

23

Number or Folder:

9

Page numbers:

4982-4982

Keyword:

CHF6001; CXC motif chemokine ligand 8 (CXCL8); budesonide; elastase; human umbilical vein endothelial cells (HUVECs); matrix metalloproteinase (MMP); myeloperoxidase (MPO); neutrophil extracellular traps (NETs); spontaneous apoptosis; tumor necrosis factor-alpha (TNF-α)

Short description of contents:

: Neutrophils, the most abundant subset of leukocytes in the blood, play a pivotal role in host response against invading pathogens. However, in respiratory diseases, excessive infiltration and activation of neutrophils can lead to tissue damage. Tanimilast-international non-proprietary name of CHF6001-is a novel inhaled phosphodiesterase 4 (PDE4) inhibitor in advanced clinical development for the treatment of chronic obstructive pulmonary disease (COPD), a chronic inflammatory lung disease where neutrophilic inflammation plays a key pathological role. Human neutrophils from healthy donors were exposed to pro-inflammatory stimuli in the presence or absence of tanimilast and budesonide-a typical inhaled corticosteroid drug-to investigate the modulation of effector functions including adherence to endothelial cells, granule protein exocytosis, release of extracellular DNA traps, cytokine secretion, and cell survival. Tanimilast significantly decreased neutrophil-endothelium adhesion, degranulation, extracellular DNA traps casting, and cytokine secretion. In contrast, it promoted neutrophil survival by decreasing both spontaneous apoptosis and cell death in the presence of pro-survival factors. The present work suggests that tanimilast can alleviate the severe tissue damage caused by massive recruitment and activation of neutrophils in inflammatory diseases such as COPD.

Product ID:

131442

Handle IRIS:

11562/1082733

Last Modified:

February 23, 2023

Bibliographic citation:

Schioppa, Tiziana; Nguyen, Hoang Oanh; Salvi, Valentina; Maugeri, Norma; Facchinetti, Fabrizio; Villetti, Gino; Civelli, Maurizio; Gaudenzi, Carolina; Passari, Mauro; Sozio, Francesca; Barbazza, Ilaria; Tamassia, Nicola; Cassatella, Marco A; Del Prete, Annalisa; Bosisio, Daniela; Tiberio, Laura, The PDE4 Inhibitor Tanimilast Restrains the Tissue-Damaging Properties of Human Neutrophils «INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES» , vol. 23 , n. 9 , 2022 , pp. 4982-4982

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo