title: Tanshinone IIA attenuates seawater aspiration-induced lung injury by inhibiting macrophage migration inhibitory factor.
abstract: Inflammation takes responsibility for the seawater aspiration-induced lung injury. Tanshinone IIA (TIIA) can protect lipopolysaccharide-induced lung injury in mice through the inhibition of inflammation, but it is not reported whether TIIA have a protective effect on lung injury induced by seawater aspiration. Macrophage migration inhibitory factor (MIF) plays an important role in acute lung injury. In this study, we observed the effect of TIIA on the seawater aspiration-induced lung injury and the role of MIF in it. Seawater was aspirated into trachea of rats to make the lung injury model. TIIA was administered to investigate its beneficial effect on seawater-induced acute lung injury. The results showed that seawater aspiration led to hyoxemia, pulmonary edema, neutrophil infiltration, and lung histopathologic changes, with the elevated MIF expression in the lung tissues and plasma. However, these changes were attenuated by TIIA. In macrophage cells we also demonstrated that TIIA could inhibit MIF expression, nuclear factor κB (NF-κB) activity and release of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) induced by seawater. Besides, pretreatment with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid (ISO-1), the MIF antagonist, elevated NF-κB and cytokines induced by seawater were also reduced markedly. Furthermore, rMIF treatment alone increased the phosphorylation level of NF-κB and release of cytokines, which was almost abolished by TIIA. Taken together, our results suggested that TIIA exert a protective effect on the seawater aspiration-induced lung injury partly through downregulation of MIF and the subsequent NF-κB activity, as well as expression of IL-6 and TNF-α.
authors: Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical University, PR China.
authors: Yong
authors: Y
authors: Zhang
authors: Bo
authors: B
authors: Zhang
authors: Dun-Quan
authors: DQ
authors: Xu
authors: Wang-Ping
authors: WP
authors: Li
authors: Min
authors: M
authors: Xu
authors: Jia-Huan
authors: JH
authors: Li
authors: Xiao-Yan
authors: XY
authors: Xie
authors: Qi-Xin
authors: QX
authors: Fan
authors: Wei
authors: W
authors: Liu
authors: De-Guang
authors: DG
authors: Mu
authors: Hai-Ying
authors: HY
authors: Dong
authors: Yan-Xia
authors: YX
authors: Wang
authors: Yan-Dong
authors: YD
authors: Nan
authors: Zhi-Chao
authors: ZC
authors: Li
authors: Fa-Guang
authors: FG
authors: Jin
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D055370:Lung Injury / Q000473:pathology / Q000517:prevention & control*; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors*; D008297:Male; D009504:Neutrophils / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012623:Seawater
chemical_list: D045784:Abietanes; D008263:Macrophage Migration-Inhibitory Factors; C021751:tanshinone