{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:07:36Z","timestamp":1790680056175,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The lungs of patients with cystic fibrosis (CF) are characterized by an exaggerated inflammation driven by secretion of IL-8 from bronchial epithelial cells and worsened by Pseudomonas aeruginosa infection. To identify novel antiinflammatory molecular targets, we previously performed a genetic study of 135 genes of the immune response, which identified the c.2534C&amp;gt;T (p.S845L) variant of phospholipase C-\u03b23 (PLCB3) as being significantly associated with mild progression of pulmonary disease. Silencing PLCB3 revealed that it potentiates the Toll-like receptor\u2019s inflammatory signaling cascade originating from CF bronchial epithelial cells. In the present study, we investigated the role of the PLCB3-S845L variant together with two synthetic mutants paradigmatic of impaired catalytic activity or lacking functional activation in CF bronchial epithelial cells. In experiments in which cells were exposed to P. aeruginosa, the supernatant of mucopurulent material from the airways of patients with CF or different agonists revealed that PLCB3-S845L has defects of 1) agonist-induced Ca2+ release from endoplasmic reticulum and rise of Ca2+ concentration, 2) activation of conventional protein kinase C isoform \u03b2, and 3) induction of IL-8 release. These results, besides identifying S845L as a loss-of-function variant, strengthen the importance of targeting PLCB3 to mitigate the CF inflammatory response in bronchial epithelial cells without blunting the immune response.<\/jats:p>","DOI":"10.1165\/rcmb.2017-0267oc","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T16:49:54Z","timestamp":1524070194000},"page":"428-436","source":"Crossref","is-referenced-by-count":18,"title":["PLCB3 Loss of Function Reduces\n                    <i>Pseudomonas aeruginosa<\/i>\n                    \u2013Dependent IL-8 Release in Cystic Fibrosis"],"prefix":"10.1093","volume":"59","author":[{"given":"Alessandro","family":"Rimessi","sequence":"first","affiliation":[{"name":"Department of Morphology, Surgery and Experimental Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentino","family":"Bezzerri","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Pathology and Diagnostics, University Hospital of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Salvatori","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Tamanini","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Pathology and Diagnostics, University Hospital of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Nigro","sequence":"additional","affiliation":[{"name":"Department of Morphology, Surgery and Experimental Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Dechecchi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Pathology and Diagnostics, University Hospital of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Santangelo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Pathology and Diagnostics, University Hospital of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Prandini","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Pathology and Diagnostics, University Hospital of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Munari","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Pathology and Diagnostics, University Hospital of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Provezza","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Pathology and Diagnostics, University Hospital of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Garreau de Loubresse","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Universit\u00e9 de Strasbourg, Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Muller","sequence":"additional","affiliation":[{"name":"Laboratoire de diagnostic g\u00e9n\u00e9tique, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla M. 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