title: Lung fibrosis induced by crystalline silica particles is uncoupled from lung inflammation in NMRI mice.
abstract: Previous studies in rats have suggested a causal relationship between progressive pulmonary inflammation and lung fibrosis induced by crystalline silica particles. We report here that, in NMRI mice, the lung response to silica particles is accompanied by a mild and non progressive pulmonary inflammation which is dispensable for the development of lung fibrosis. We found that glucocorticoid (dexamethasone) dramatically reduced lung injury, cellular inflammation and pro-inflammatory cytokine expression (TNF-α, IL-1β and KC) but had no significant effect on silica-induced lung fibrosis and expression of the fibrogenic and suppressive cytokines TGF-β and IL-10 in mice. Other anti-inflammatory molecules such as the COX inhibitor piroxicam or the phosphodiesterase 5 inhibitor sildenafil also reduced lung inflammation without modifying collagen, TGF-β or IL-10 lung content. Our findings indicate that the development of lung fibrosis in silica-treated NMRI mice is not driven by inflammatory lung responses and suggest that suppressive cytokines may represent critical fibrotic factors and potential therapeutic targets in silicosis.
authors.affiliation: Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Brussels, Belgium. virginie.rabolli@uclouvain.be
authors.forename: Virginie
authors.initials: V
authors.lastname: Rabolli
authors.forename: Sandra
authors.initials: S
authors.lastname: Lo Re
authors.forename: Francine
authors.initials: F
authors.lastname: Uwambayinema
authors.forename: Yousof
authors.initials: Y
authors.lastname: Yakoub
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
authors.forename: François
authors.initials: F
authors.lastname: Huaux
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002452:Cell Count; D003094:Collagen / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010894:Piroxicam / Q000494:pharmacology; D011014:Pneumonia / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology; D011687:Purines / Q000494:pharmacology; D000068677:Sildenafil Citrate; D012822:Silicon Dioxide / Q000633:toxicity*; D013450:Sulfones / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: D016861:Cyclooxygenase Inhibitors; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D010894:Piroxicam; D012822:Silicon Dioxide; D003094:Collagen; D000068677:Sildenafil Citrate; D007770:L-Lactate Dehydrogenase