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

Abstract

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.

Immunomodulatory effects of recombinant BCG expressing MSP-1C ofPlasmodium falciparumon LPS- or LPS+IFN-γ-stimulated J774A.1 cells

“…63,64 NO and iNOS productions have been reported to be correlated with TNF-α and IL-1β productions since both processes involved NF-κB and MAPKinases regulation. 65,66 In this study, both BCG and rBCG infections also stimulated higher production of TNF-α and IL-1β, suggesting the involvement of these cytokines in stimulating the production of NO and iNOS by the macrophages. Although TNF-α and IL-1β are associated with severe malaria and cerebral malaria in children, 67,68 they are also important for parasite killing during malaria infection.…”

Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis

“…Reports on pharmacological properties of limonene are scarce, but it has been shown to have antimicrobial properties (Bevilacqua et al, 2010) and anti-inflammatory effects in a mouse model of LPS-induced acute lung injury by suppressing MAPK and NF-κB pathways (Chi et al, 2012). The results presented here only partially agree with this study, since limonene inhibited NF-κB and p38 activation, but did not affect IL-1β-induced JNK and actually potentiated ERK1/2 activation, suggesting that this compound has cell-and/or stimulus-specific effects.…”

The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury in mice

“…Unfortunately, no effective drug has been found in clinical [14]. LPS, a critical trigger of lung inflammatory response in ALI, induces a large and acute accumulation of neutrophils responsible for the inflammatory pathogenesis [15].…”

“…LPS, a critical trigger of lung inflammatory response in ALI, induces a large and acute accumulation of neutrophils responsible for the inflammatory pathogenesis [15]. The pathological progression of ALI is highly related to airspaces alveolar-capillary barrier, noncardiogenic edema and lung parenchyma injury and the release of inflammatory mediators including TNF-α, IL-6, and IL-1β [16][17][18]. Inflammatory cytokines, which emerge in the early stage of inflammation pathogenic process, play an essential role in ALI and conduce to the severity of lung injury [19].…”