title: Lentivirus expressing soluble ST2 alleviates bleomycin-induced pulmonary fibrosis in mice.
abstract: It has been shown that the expression of ST2, a receptor of interleukin (IL)-33, is elevated in the lungs of idiopathic pulmonary fibrosis patients and bleomycin-induced mouse models, however its contribution to the development of pulmonary fibrosis has yet to be tested. In the present study, we treated mice by intranasal instillation of lentivirus expressing soluble ST2 and evaluated lung inflammation and fibrosis in the bleomycin-induced pulmonary fibrosis mouse model. We found that ST2 lentivirus treatment significantly improved survival rate and reduced weight loss compared with controls treated with empty lentivirus. Furthermore, ST2 treatment profoundly attenuated the pulmonary inflammatory cell infiltration and fibrotic changes. Finally, ST2 treatment markedly lowered the levels of IL-4, IL-6, IL-13, IL-33, monocyte chemoattractant protein-1, and transforming growth factor-β1, whereas it increased the levels of interferon-γ in bronchoalveolar lavage fluid. The results indicate that ST2 might prevent bleomycin-induced pulmonary fibrosis possibly through downregulating proinflammatory and profibrotic mediators. This study suggests that lentivirus expressing soluble ST2 might represent an effective therapeutic approach in the treatment of pulmonary fibrotic diseases.
authors.affiliation: Department of Immunology, Ningbo University School of Medicine, Ningbo, China.
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Immunology, Ningbo University School of Medicine, Ningbo, China. Electronic address: yanli319@yahoo.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, Ningbo University School of Medicine, Ningbo, China.
authors.forename: Xiuhe
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Immunology, Ningbo University School of Medicine, Ningbo, China.
authors.forename: Xianli
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Immunology, Ningbo University School of Medicine, Ningbo, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Immunology, Ningbo University School of Medicine, Ningbo, China. Electronic address: limingcai@nbu.edu.cn.
authors.forename: Mingcai
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33 / Q000819:agonists; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000628:therapy*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000628:therapy*; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; C486189:Il1rl1 protein, mouse; D018836:Inflammation Mediators; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D018123:Receptors, Interleukin; D001761:Bleomycin
keywords: Collagen; Inflammation; Interleukin-33; Lentivirus vector; Pulmonary fibrosis; ST2