Suppression of MAPK and NF-κB Pathways by Limonene Contributes to Attenuation of Lipopolysaccharide-Induced Inflammatory Responses in Acute Lung Injury

• Published in: Inflammation 2013-04, Vol.36 (2), p.501-511
• Main Authors: Chi, Gefu, Wei, Miaomiao, Xie, Xianxing, Soromou, L. W., Liu, Fang, Zhao, Shuhua
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - drug therapy; Acute Lung Injury - immunology; Animals; Anti-Inflammatory Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Bronchoalveolar Lavage Fluid; Cyclohexenes - pharmacology; Dexamethasone - pharmacology; Immunology; Inflammation - chemically induced; Inflammation - drug therapy; Interleukins - metabolism; Internal Medicine; Lipopolysaccharides; Lung - immunology; Lung - metabolism; Male; MAP Kinase Signaling System - drug effects; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - immunology; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-kappa B p50 Subunit - metabolism; Pathology; Peroxidase - metabolism; Pharmacology/Toxicology; Phosphorylation - drug effects; Rheumatology; Terpenes - pharmacology; Transcription Factor RelA - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-012-9571-1

The present study aimed to investigate the protective role of limonene in lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS (0.5 mg/kg), and limonene (25, 50, and 75 mg/kg) was injected intraperitoneally 1 h prior to LPS administration. After 12 h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Limonene pretreatment at doses of 25, 50, and 75 mg/kg decreased LPS-induced evident lung histopathological changes, lung wet-to-dry weight ratio, and lung myeloperoxidase activity. In addition, pretreatment with limonene inhibited inflammatory cells and proinflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in BALF. Furthermore, we demonstrated that limonene blocked the phosphorylation of IκBα, nuclear factor-κB (NF-κB) p65, p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase in LPS-induced ALI. The results presented here suggest that the protective mechanism of limonene may be attributed partly to decreased production of proinflammatory cytokines through the inhibition of NF-κB and MAPK activation.