{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:22:33Z","timestamp":1790277753994,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of the University and Research","award":["MUR-PRIN 20178ALPCM_005"],"award-info":[{"award-number":["MUR-PRIN 20178ALPCM_005"]}]},{"name":"Italian Ministry of the University and Research","award":["MUR-PRIN 20177J4E75_004"],"award-info":[{"award-number":["MUR-PRIN 20177J4E75_004"]}]},{"name":"Italian Ministry of the University and Research","award":["AIRC IG-20339"],"award-info":[{"award-number":["AIRC IG-20339"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro","award":["MUR-PRIN 20178ALPCM_005"],"award-info":[{"award-number":["MUR-PRIN 20178ALPCM_005"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro","award":["MUR-PRIN 20177J4E75_004"],"award-info":[{"award-number":["MUR-PRIN 20177J4E75_004"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro","award":["AIRC IG-20339"],"award-info":[{"award-number":["AIRC IG-20339"]}]},{"name":"University of Brescia","award":["MUR-PRIN 20178ALPCM_005"],"award-info":[{"award-number":["MUR-PRIN 20178ALPCM_005"]}]},{"name":"University of Brescia","award":["MUR-PRIN 20177J4E75_004"],"award-info":[{"award-number":["MUR-PRIN 20177J4E75_004"]}]},{"name":"University of Brescia","award":["AIRC IG-20339"],"award-info":[{"award-number":["AIRC IG-20339"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2014is 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\u2014a 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.<\/jats:p>","DOI":"10.3390\/ijms23094982","type":"journal-article","created":{"date-parts":[[2022,4,30]],"date-time":"2022-04-30T05:44:07Z","timestamp":1651297447000},"page":"4982","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The PDE4 Inhibitor Tanimilast Restrains the Tissue-Damaging Properties of Human Neutrophils"],"prefix":"10.3390","volume":"23","author":[{"given":"Tiziana","family":"Schioppa","sequence":"first","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoang Oanh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Salvi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3931-0412","authenticated-orcid":false,"given":"Norma","family":"Maugeri","sequence":"additional","affiliation":[{"name":"Autoimmunity and Vascular Inflammation Unit, IRCCS San Raffaele Scientific Institute, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Facchinetti","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology and Translational Science, Corporate Pre-Clinical R&D, Chiesi Farmaceutici S.p.A., 43122 Parma, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0502-7865","authenticated-orcid":false,"given":"Mauro","family":"Passari","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Sozio","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Barbazza","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2990-3003","authenticated-orcid":false,"given":"Nicola","family":"Tamassia","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of General Pathology, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A.","family":"Cassatella","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of General Pathology, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3738-412X","authenticated-orcid":false,"given":"Annalisa","family":"Del Prete","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6276-5365","authenticated-orcid":false,"given":"Daniela","family":"Bosisio","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0482-9898","authenticated-orcid":false,"given":"Laura","family":"Tiberio","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,29]]},"reference":[{"key":"ref_1","first-page":"5273201","article-title":"Targets of Neutrophil Influx and Weaponry: Therapeutic Opportunities for Chronic Obstructive Airway Disease","volume":"2017","author":"Root","year":"2017","journal-title":"J. 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