title: Pulmonary overexpression of IL-10 augments lung fibrosis and Th2 responses induced by silica particles.
abstract: Chronic inflammation and proinflammatory cytokines as well as T helper type 2 (Th2) cytokines have been involved in the pathogenesis of pulmonary injury and lung fibrosis. The actual role of IL-10 in lung fibrosis is still unclear because this cytokine has been identified as Th2 but possesses strong anti-inflammatory properties. To better dissect the potential role of IL-10 in silica-induced lung fibrosis, IL-10 was overexpressed in the lung of mice by adenoviral gene transfer during the inflammatory (administered at day -1) or the fibrotic (administered at day +30) stages of the disease. Pulmonary overexpression of IL-10 during both silica-induced lung inflammation and fibrosis exacerbated the fibrotic lesions as estimated by the measurement of hydroxyproline and other biochemical and histological markers. Increased expression of IL-10 significantly enhanced the number of lung lymphocytes and bronchoalveolar lavage fluid IgG1 but not IgG2a levels, indicating the induction of a Th2-like immune response. In addition, the production of the profibrotic Th2 cytokines IL-4 and IL-13 was also significantly increased upon IL-10 overexpression. No difference in transforming growth factor-beta or PGE(2) production was noted after adenoviral IL-10 treatment of silica-treated mice. Together, these data indicate that the increased expression of IL-10 significantly contributed to silica-induced lung fibrosis by exacerbating the Th2 response and the production of the profibrotic cytokines IL-4 and IL-13.
authors.affiliation: Unit of Industrial Toxicology and Occupational Medicine, University Hospital of Mont Godinne, Université Catholique de Louvain, 30.54, Clos Chapelle-aux-Champs, 1200 Brussels, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Barbarin
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
authors.forename: Monique
authors.initials: M
authors.lastname: Delos
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
authors.forename: Francois
authors.initials: F
authors.lastname: Huaux
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000276:immunology* / Q000503:physiopathology*; D012822:Silicon Dioxide; D012829:Silicosis / Q000276:immunology* / Q000503:physiopathology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018793:Interleukin-13; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D012822:Silicon Dioxide; D015232:Dinoprostone