title: NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung.
abstract: In this study we investigated the implication of NLRP3 inflammasomes in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-usual interstitial pneumonia (RA-UIP).NLRP3 inflammasome activation at baseline and following stimulation with lipopolysaccharide/ATP was evaluated by measuring interleukin (IL)-1β and IL-18 levels released in the bronchoalveolar lavage fluid (BALF) fluid and by cultures of BALF cells. IL-1β and IL-18 levels were significantly elevated in the BALF and BALF macrophage cultures from RA-UIP patients, consistent with pre-existing inflammasome activation in these patients. In contrast, in IPF, BALF levels of IL-1β were significantly less elevated relative to RA-UIP and IL-18 was lower than controls. Furthermore, upon inflammasome stimulation, IPF BALF macrophage cultures failed to upregulate IL-1β and partly IL-18 secretion, in contrast to controls, which showed robust IL-1β and IL-18 upregulation. Interestingly, RA-UIP BALF cell cultures treated with lipopolysaccharide/ATP showed a potent stimulation of IL-18 secretion but not IL-1β, the latter being already elevated in the unstimulated cultures, while examination of the intracellular IL-1β levels in RA-UIP BALF cells upon NLRP3 inflammasome stimulation showed a significant upregulation of IL-1β suggesting the NLRP3 pathway could be further activated.Taken together, our results suggest distinct inflammasome activation profiles between autoimmune and idiopathic lung fibrosis.
authors.affiliation: Laboratory of Cellular and Molecular Pneumonology, Medical School, University of Crete, Heraklion, Crete, Greece Both authors contributed equally.
authors.forename: Ismini
authors.initials: I
authors.lastname: Lasithiotaki
authors.affiliation: Laboratory of Cellular and Molecular Pneumonology, Medical School, University of Crete, Heraklion, Crete, Greece Dept of Thoracic Medicine, Interstitial Lung Disease Unit, University Hospital of Heraklion, Heraklion, Crete, Greece Both authors contributed equally.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Giannarakis
authors.affiliation: Laboratory of Cellular and Molecular Pneumonology, Medical School, University of Crete, Heraklion, Crete, Greece.
authors.forename: Eliza
authors.initials: E
authors.lastname: Tsitoura
authors.affiliation: Laboratory of Cellular and Molecular Pneumonology, Medical School, University of Crete, Heraklion, Crete, Greece kantoniou@med.uoc.gr.
authors.forename: Katerina D
authors.initials: KD
authors.lastname: Samara
authors.affiliation: Laboratory of Cellular and Molecular Pneumonology, Medical School, University of Crete, Heraklion, Crete, Greece.
authors.forename: George A
authors.initials: GA
authors.lastname: Margaritopoulos
authors.affiliation: Dept of Rheumatology and Clinical Immunology and Allergy, University of Crete, Medical School, Heraklion, Crete, Greece.
authors.forename: Christiana
authors.initials: C
authors.lastname: Choulaki
authors.affiliation: Laboratory of Cellular and Molecular Pneumonology, Medical School, University of Crete, Heraklion, Crete, Greece.
authors.forename: Eirini
authors.initials: E
authors.lastname: Vasarmidi
authors.affiliation: Laboratory of Cellular and Molecular Pneumonology, Medical School, University of Crete, Heraklion, Crete, Greece Dept of Thoracic Medicine, Interstitial Lung Disease Unit, University Hospital of Heraklion, Heraklion, Crete, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tzanakis
authors.affiliation: Dept of Radiology, University Hospital of Heraklion, Heraklion, Crete, Greece.
authors.forename: Argyro
authors.initials: A
authors.lastname: Voloudaki
authors.affiliation: Dept of Rheumatology and Clinical Immunology and Allergy, University of Crete, Medical School, Heraklion, Crete, Greece.
authors.forename: Prodromos
authors.initials: P
authors.lastname: Sidiropoulos
authors.affiliation: Dept of Thoracic Medicine, Interstitial Lung Disease Unit, University Hospital of Heraklion, Heraklion, Crete, Greece.
authors.forename: Nikolaos M
authors.initials: NM
authors.lastname: Siafakas
authors.affiliation: Laboratory of Cellular and Molecular Pneumonology, Medical School, University of Crete, Heraklion, Crete, Greece Dept of Thoracic Medicine, Interstitial Lung Disease Unit, University Hospital of Heraklion, Heraklion, Crete, Greece.
authors.forename: Katerina M
authors.initials: KM
authors.lastname: Antoniou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D005260:Female; D006115:Greece; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism*; D058847:Inflammasomes / Q000378:metabolism*; D053703:Interleukin-11 Receptor alpha Subunit / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D017563:Lung Diseases, Interstitial / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C508428:IL11RA protein, human; D058847:Inflammasomes; D053703:Interleukin-11 Receptor alpha Subunit; D020382:Interleukin-18; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human