{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:13:59Z","timestamp":1791242039110,"version":"4.1.0"},"reference-count":53,"publisher":"European Respiratory Society (ERS)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2010,3,31]]},"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:p>Cystic fibrosis (CF) is due to mutations in the CF transmembrane conductance regulator gene<jats:italic>CFTR<\/jats:italic>. CF is characterised by mucus dehydration, chronic bacterial infection and inflammation, and increased levels of cytosolic phospholipase A2\u03b1 (cPLA2\u03b1) products in airways.<\/jats:p><jats:p>We aimed to examine the role of cPLA2\u03b1 in the modulation of mucus production and inflammation in CFTR-deficient mice and epithelial cells. Mucus production was assessed using histological analyses, immuno-histochemistry and MUC5AC ELISA. cPLA2\u03b1 activation was measured using an enzymatic assay and lung inflammation determined by histological analyses and polymorphonuclear neutrophil counts in bronchoalveolar lavages.<\/jats:p><jats:p>In lungs from<jats:italic>Cftr<jats:sup>-\/-<\/jats:sup><\/jats:italic>mice, lipopolysaccharide induced mucus overproduction and MUC5AC expression associated with an increased cPLA2\u03b1 activity. Mucus overproduction was mimicked by instillation of the cPLA2\u03b1 product arachidonic acid, and abolished by either a cPLA2\u03b1 null mutation or pharmacological inhibition. An increased cPLA2\u03b1 activity was observed in bronchial explants from CF patients. CFTR silencing induced cPLA2\u03b1 activation and MUC5AC expression in bronchial human epithelial cells. This expression was enhanced by arachidonic acid and reduced by cPLA2\u03b1 inhibition. However, inhibition of CFTR chloride transport function had no effect on MUC5AC expression.<\/jats:p><jats:p>Reduction of CFTR expression increased cPLA2\u03b1 activity. This led to an enhanced mucus production in airway epithelia independent of CFTR chloride transport function. cPLA2\u03b1 represents a suitable new target for therapeutic intervention in CF.<\/jats:p>","DOI":"10.1183\/09031936.00183409","type":"journal-article","created":{"date-parts":[[2010,4,23]],"date-time":"2010-04-23T00:46:18Z","timestamp":1271983578000},"page":"1120-1130","source":"Crossref","is-referenced-by-count":34,"title":["Critical role of cytosolic phospholipase A2\u03b1 in bronchial mucus hypersecretion in CFTR-deficient mice"],"prefix":"10.1183","volume":"36","author":[{"given":"F.","family":"Dif","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y-Z.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P-R.","family":"Burgel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ollero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Leduc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Aarbiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Borot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Garcia-Verdugo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Chignard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Israel-Biet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Kita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.J.","family":"Scholte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Touqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2010,4,22]]},"reference":[{"key":"2024102020165960000_36.5.1120.1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90148-8"},{"key":"2024102020165960000_36.5.1120.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01271.x"},{"key":"2024102020165960000_36.5.1120.3","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.1950200203"},{"key":"2024102020165960000_36.5.1120.4","first-page":"1075","article-title":"Early pulmonary inflammation in infants with cystic fibrosis","volume":"151","author":"Khan","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"key":"2024102020165960000_36.5.1120.5","doi-asserted-by":"publisher","DOI":"10.1038\/359195a0"},{"key":"2024102020165960000_36.5.1120.6","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.94.07091678"},{"key":"2024102020165960000_36.5.1120.7","first-page":"L413","article-title":"Mucins: structure, function, and role in pulmonary diseases","volume":"263","author":"Rose","year":"1992","journal-title":"Am J Physiol"},{"key":"2024102020165960000_36.5.1120.8","doi-asserted-by":"publisher","DOI":"10.1016\/S1526-0550(02)00007-0"},{"key":"2024102020165960000_36.5.1120.9","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00010.2005"},{"key":"2024102020165960000_36.5.1120.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra043184"},{"key":"2024102020165960000_36.5.1120.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(98)00010-6"},{"key":"2024102020165960000_36.5.1120.12","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.062190"},{"key":"2024102020165960000_36.5.1120.13","doi-asserted-by":"publisher","DOI":"10.1053\/rmed.2001.1221"},{"key":"2024102020165960000_36.5.1120.14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38662"},{"key":"2024102020165960000_36.5.1120.15","doi-asserted-by":"publisher","DOI":"10.1097\/01.mcp.0000198064.27586.37"},{"key":"2024102020165960000_36.5.1120.16","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.26.1.4618"},{"key":"2024102020165960000_36.5.1120.17","doi-asserted-by":"publisher","DOI":"10.1080\/15412550500218098"},{"key":"2024102020165960000_36.5.1120.18","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/148.4_Pt_1.896"},{"key":"2024102020165960000_36.5.1120.19","doi-asserted-by":"publisher","DOI":"10.1124\/mol.62.5.1112"},{"key":"2024102020165960000_36.5.1120.20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007116"},{"key":"2024102020165960000_36.5.1120.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2006.05.003"},{"key":"2024102020165960000_36.5.1120.22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1388-1981(00)00105-0","article-title":"The expanding superfamily of phospholipase A(2) enzymes: classification and characterization","volume":"1488","author":"Six","year":"2000","journal-title":"Biochim Biophys Acta"},{"key":"2024102020165960000_36.5.1120.23","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.2.589"},{"key":"2024102020165960000_36.5.1120.24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200113416"},{"key":"2024102020165960000_36.5.1120.25","doi-asserted-by":"publisher","DOI":"10.1038\/37635"},{"key":"2024102020165960000_36.5.1120.26","doi-asserted-by":"publisher","DOI":"10.1038\/nm0502-480"},{"key":"2024102020165960000_36.5.1120.27","doi-asserted-by":"publisher","DOI":"10.1038\/37622"},{"key":"2024102020165960000_36.5.1120.28","doi-asserted-by":"publisher","DOI":"10.1126\/science.257.5073.1083"},{"key":"2024102020165960000_36.5.1120.29","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00396.2002"},{"key":"2024102020165960000_36.5.1120.30","doi-asserted-by":"crossref","first-page":"L1083","DOI":"10.1152\/ajplung.2000.279.6.L1083","article-title":"Neutrophil recruitment and increased permeability during acute lung injury induced by lipopolysaccharide","volume":"279","author":"Chignard","year":"2000","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2024102020165960000_36.5.1120.31","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.20.5.3446"},{"key":"2024102020165960000_36.5.1120.32","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.24.1.4122"},{"key":"2024102020165960000_36.5.1120.33","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.10.5948"},{"key":"2024102020165960000_36.5.1120.34","doi-asserted-by":"publisher","DOI":"10.1007\/BF02533973"},{"key":"2024102020165960000_36.5.1120.35","doi-asserted-by":"crossref","first-page":"5613","DOI":"10.4049\/jimmunol.151.10.5613","article-title":"Increased synthesis and secretion of a 14-kDa phospholipase A2 by guinea pig alveolar macrophages. Dissociation from arachidonic acid liberation and modulation by dexamethasone","volume":"151","author":"Hidi","year":"1993","journal-title":"J Immunol"},{"key":"2024102020165960000_36.5.1120.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2006.05.002"},{"key":"2024102020165960000_36.5.1120.37","doi-asserted-by":"crossref","first-page":"L531","DOI":"10.1152\/ajplung.00455.2001","article-title":"Neutrophil elastase induces mucin production by ligand-dependent epidermal growth factor receptor activation","volume":"283","author":"Kohri","year":"2002","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2024102020165960000_36.5.1120.38","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2003.018879"},{"key":"2024102020165960000_36.5.1120.39","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00403.2005"},{"key":"2024102020165960000_36.5.1120.40","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00181.2006"},{"key":"2024102020165960000_36.5.1120.41","doi-asserted-by":"publisher","DOI":"10.1038\/ng0495-351"},{"key":"2024102020165960000_36.5.1120.42","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.19.6.3194"},{"key":"2024102020165960000_36.5.1120.43","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.17.4.2734"},{"key":"2024102020165960000_36.5.1120.44","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1089\/dna.1997.16.749","article-title":"Cystic fibrosis gene mutation (deltaF508) is associated with an intrinsic abnormality in Ca2+-induced arachidonic acid release by epithelial cells","volume":"16","author":"Miele","year":"1997","journal-title":"DNA Cell Biol"},{"key":"2024102020165960000_36.5.1120.45","doi-asserted-by":"crossref","first-page":"8","DOI":"10.4267\/10608\/4270","article-title":"Une homologie frappante entre CFTR et les annexines [A striking homology between CFTR and annexins]","volume":"7","author":"Chap","year":"1991","journal-title":"M\u00e9decine\/Science"},{"key":"2024102020165960000_36.5.1120.46","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(94)90281-X"},{"key":"2024102020165960000_36.5.1120.47","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)02326-7"},{"key":"2024102020165960000_36.5.1120.48","doi-asserted-by":"publisher","DOI":"10.1038\/ng1192-240"},{"key":"2024102020165960000_36.5.1120.49","doi-asserted-by":"crossref","first-page":"6076","DOI":"10.1002\/j.1460-2075.1994.tb06954.x","article-title":"Conformational maturation of CFTR but not its mutant counterpart (\u03b4 F508) occurs in the endoplasmic reticulum and requires ATP","volume":"13","author":"Lukacs","year":"1994","journal-title":"Embo J"},{"key":"2024102020165960000_36.5.1120.50","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E07-02-0126"},{"key":"2024102020165960000_36.5.1120.51","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.bbadis.2007.06.006","article-title":"Annexin V is directly involved in cystic fibrosis transmembrane conductance regulator's chloride channel function","volume":"1772","author":"Trouve","year":"2007","journal-title":"Biochim Biophys Acta"},{"key":"2024102020165960000_36.5.1120.52","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200400895"},{"key":"2024102020165960000_36.5.1120.53","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M500019-MCP200"}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/09031936.00183409","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T06:32:43Z","timestamp":1740378763000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/09031936.00183409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4,22]]},"references-count":53,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2010,10,31]]},"published-print":{"date-parts":[[2010,11]]}},"alternative-id":["10.1183\/09031936.00183409"],"URL":"https:\/\/doi.org\/10.1183\/09031936.00183409","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4,22]]}}}