title: Rapid pulmonary fibrosis induced by acute lung injury via a lipopolysaccharide three-hit regimen.
abstract: Based on the common characteristic of severe acute respiratory syndrome (SARS) and highly pathogenic avian influenza and the mechanism of inflammation and fibrosis, it is speculated that there should exist a fundamental pathological rule that severe acute lung injury (ALI)-induced rapid pulmonary fibrosis is caused by various etiological factors, such as SARS coronavirus, H5N1-virus, or other unknown factors, and also by lipopolysaccharide (LPS), the most common etiological factor. The investigation employed intratracheally, and intraperitoneally and intratracheally applied LPS three-hit regimen, compared with bleomycin-induced chronic pulmonary fibrosis. Inflammatory damage and fibrosis were evaluated, and the molecular mechanism was analyzed according to Th1/Th2 balance, Sma- and MAD-related proteins (Smads) and signal transducer and activator of transcriptions (STATs) expression. The results suggested that rapid pulmonary fibrosis could be induced by ALI via LPS three-hits. The period from 3-7 days in the LPS group was the first rapid pulmonary fibrosis stage, whereas the second fast fibrosis stage occurred on days 14-21. Th2 cell polarization, Smad4 and Smad7 should be the crucial molecular mechanism of ALI-induced rapid fibrosis. The investigation was not only performed to establish a new rapid pulmonary fibrosis model, but also to provide the elicitation for mechanism of ALI changed into the rapid pulmonary fibrosis.
authors.affiliation: Department of Anatomy, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Shaohui
authors.initials: S
authors.lastname: Du
authors.forename: Lina
authors.initials: L
authors.lastname: Yang
authors.forename: Yangyan
authors.initials: Y
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Yinghai
authors.initials: Y
authors.lastname: Cui
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Chen
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Li
authors.forename: Saixia
authors.initials: S
authors.lastname: Zhang
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhou
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wei
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Yao
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000150:complications / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001761:Bleomycin / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000032:analysis; D008070:Lipopolysaccharides / Q000276:immunology*; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D050791:STAT Transcription Factors / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051785:Smad Proteins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000903:Antibiotics, Antineoplastic; D016207:Cytokines; D008070:Lipopolysaccharides; D050791:STAT Transcription Factors; D051785:Smad Proteins; D001761:Bleomycin; D003907:Dexamethasone; D006909:Hydroxyproline