IL-13 immunotoxin accelerates resolution of lung pathological changes triggered by silica particles in mice.

摘要: Instillation of silica into the lungs rodents results in pathological changes that strongly mimic human silicosis, an occupational lung disease marked by restrictive airway obstruction, inflammation, and fibrosis. Because IL-13 is a pivotal proinflammatory fibrogenic cytokine, we examined whether recombinant immunotoxin comprised mutated form Pseudomonas exotoxin (IL-13-PE) might affect features experimental silicosis. Mice received single intranasal instillation particles were treated with IL-13-PE every other day from days 21 to 27 postsilica. The sensitivity putative cell targets was also assessed vitro settings. Upregulation IL-13, its receptor subunits IL-13Rα1 IL-13Rα2, shared IL-4Rα associated development granulomatous inflammation triggered silica. inhibited silica-induced granuloma fibrotic responses noted at 24 h 15 d after last treatment. TNF-α, TGF-β, chemokines, as well increased collagen deposition hyperreactivity methacholine all clearly sensitive IL-13-PE. In addition, both IL-13-induced proliferation cultured fibroblasts silicotic mice IL-8 generation A549 cells. conclusion, our findings show therapeutic treatment can reverse important caused inhalation particles, suggesting this promising molecular template drug discovery for