Rapid pulmonary fibrosis induced by acute lung injury via a lipopolysaccharide three-hit regimen.
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.
Li
Hui
H
Department of Anatomy, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.
Du
Shaohui
S
Yang
Lina
L
Chen
Yangyan
Y
Huang
Wei
W
Zhang
Rong
R
Cui
Yinghai
Y
Yang
Jun
J
Chen
Dongfeng
D
Li
Yiwei
Y
Zhang
Saixia
S
Zhou
Jianhong
J
Wei
Zhijun
Z
Yao
Zhibin
Z
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
D000893:Anti-Inflammatory Agents; D000903:Antibiotics, Antineoplastic; D016207:Cytokines; D008070:Lipopolysaccharides; D050791:STAT Transcription Factors; D051785:Smad Proteins; D001761:Bleomycin; D003907:Dexamethasone; D006909:Hydroxyproline