Isotetrandrine protects against lipopolysaccharide-induced acute lung injury by suppression of mitogen-activated protein kinase and nuclear factor-kappa B

• Published in: The Journal of surgical research 2014-04, Vol.187 (2), p.596-604
• Main Authors: Liang, Xian-ming, PhD, Guo, Gui-fang, MD, Huang, Xian-hui, PhD, Duan, Wen-long, PhD, Zeng, Zhen-ling, PhD
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - chemically induced; Acute Lung Injury - drug therapy; Acute Lung Injury - metabolism; ALI; Animals; Benzylisoquinolines - chemistry; Benzylisoquinolines - pharmacology; Bronchoalveolar Lavage Fluid; Cell Line; Disease Models, Animal; Dose-Response Relationship, Drug; Immunosuppressive Agents - chemistry; Immunosuppressive Agents - pharmacology; Inflammation; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Isotetrandrine (ITD); Lipopolysaccharides - pharmacology; LPS; Male; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - metabolism; Peroxidase - metabolism; Pulmonary Edema - chemically induced; Pulmonary Edema - drug therapy; Pulmonary Edema - metabolism; Surgery
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2013.11.003

Abstract Background Mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways are pleiotropic regulator of many genes involved in lipopolysaccharide (LPS)-induced acute lung injury (ALI). The present study aimed to reveal the protective effect of isotetrandrine (ITD), a small molecule inhibitor, on various aspects of LPS-induced inflammation in vitro and in vivo. Methods In vitro , RAW 264.7 cells were pretreated with different dose of ITD 1 h before treatment with 1 mg/L of LPS. In vivo , to induce ALI, male BALB/c mice were injected intranasally with LPS and treated with ITD (20 and 40 mg/kg) 1 h before LPS. Results In vitro , the cytokine levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in supernatant were reduced by ITD. Meanwhile, in vivo , pulmonary inflammatory cell infiltration, myeloperoxidase activity, total cells, neutrophils, macrophages, along with the levels of tumor necrosis factor-α, IL-1β, and IL-6 in bronchoalveolar lavage fluid were dose-dependently attenuated by ITD. Furthermore, our data showed that ITD significantly inhibited the activation of MAPK and NF-κB, which are induced by LPS in ALI model. Conclusions These results suggested that ITD dose-dependently suppressed the severity of LPS-induced ALI by inactivation of MAPK and NF-κB, which may involve the inhibition of tissue oxidative injury and pulmonary inflammatory process.