title: Tanshinone IIA inhibits lipopolysaccharide-induced MUC1 overexpression in alveolar epithelial cells.
abstract: The anti-inflammatory function of tanshinone IIA (TIIA), an active natural compound from Chinese herbal medicine Danshen, has been well recognized, and therefore TIIA has been widely used to treat various inflammatory conditions associated with cardiac and lung diseases. Mucin 1 (Muc1) plays important anti-inflammatory roles in resolution of acute lung inflammation. In this study, we investigated the effects of TIIA on LPS-induced acute lung inflammation, as well as its relationship to Muc1 expression in mouse lung and MUC1 in human alveolar epithelial cells. TIIA pretreatment significantly inhibited LPS-induced pulmonary inflammation in both Muc1 wild-type (Muc1(+/+)) and knockout (Muc1(-/-)) mice, as manifested by reduced neutrophil infiltration and reduced TNF-α and keratinocyte chemoattractant levels in bronchoalveolar lavage fluid. The inhibitory effects of TIIA on airway inflammation were associated with reduced expression of Muc1 in Muc1(+/+) mouse lung. Moreover, pretreatment with TIIA significantly inhibited LPS-induced MUC1 expression and TNF-α release in A549 alveolar epithelial cells. TNF-α upregulated MUC1 mRNA and protein expression in A549 cells, which was inhibited by pretreatment with TIIA. The LPS-induced MUC1 expression was blocked when A549 cells were transfected with siRNA targeting for TNF-α receptor 1. Furthermore, TIIA inhibited LPS-induced nuclear translocation of NF-κB and upregulation of Toll-like receptor 4 in A549 cells. Taken together, these results demonstrate that TIIA suppressed LPS-induced acute lung inflammation regardless of the presence of Muc1, and TIIA inhibited LPS- and TNF-α-induced MUC1/Muc1 expression in airway epithelial cells, suggesting that MUC1/Muc1 does not account for the mechanisms of the anti-inflammatory effects of TIIA in the airway.
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China;
authors.forename: Kedong
authors.initials: K
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xu
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.forename: Chenting
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhengtu
authors.initials: Z
authors.lastname: Li
authors.forename: Xuefang
authors.initials: X
authors.lastname: Gong
authors.forename: Wenju
authors.initials: W
authors.lastname: Lu
mesh_terms: D045784:Abietanes / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018396:Mucin-1 / Q000096:biosynthesis*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D011897:Random Allocation; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D045784:Abietanes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D018396:Mucin-1; C577056:muc1 protein, mouse; C021751:tanshinone
keywords: Mucin 1; Toll-like receptor 4; alveolar epithelial cells; lipopolysaccharide; tanshinone IIA; tumor necrosis factor-α