Sesamin Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibition of TLR4 Signaling Pathways
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ORIGINAL ARTICLE
Sesamin Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibition of TLR4 Signaling Pathways Li Qiang,1 Jiang Yuan,2 Jiang Shouyin,1 Li Yulin,1 Jiang Libing,1 and Wang Jian-an1,3
Abstract—Recent studies suggested that TLR4 signaling pathways played an important role in the development of LPS-induced acute lung injury (ALI). Sesamin, a sesame lignan exacted from sesame seeds, has been shown to exhibit significant anti-inflammatory activity. The purpose of this study was to investigate the anti-inflammatory effects of sesamin on LPS-induced ALI in mice. Mice ALI model was induced by intratracheal instillation of LPS. Sesamin was given 1 h after LPS challenge. Our results showed that sesamin inhibited LPS-induced lung pathological change, edema, and myeloperoxidase (MPO) activity. Sesamin suppressed LPS-induced inflammatory cytokines TNF-α, IL-6, and IL-1β production. Furthermore, sesamin inhibited LPS-induced TLR4 expression and NF-κB activation. In conclusion, the results of this study indicated that sesamin protected against LPS-induced ALI by inhibition of TLR4 signaling pathways. KEY WORDS: sesamin; LPS; acute lung injury; NF-κB; TLR4.
INTRODUCTION Acute lung injury is a critical illness syndrome characterized by serious lung inflammation and increased capillary permeability [1]. Many factors such as sepsis, shock, trauma, and burns could lead to acute lung injury (ALI) [2]. LPS has been identified as the main factor that causes ALI [3]. LPS activates TLR4 signaling pathway, which subsequently leads to the activation of NF-κB [4, 5]. NF-κB, an important transcription factor, has been known to play critical roles in the regulation of inflammatory cytokine production [6]. These inflammatory cytokines leads to asthmatic pathological alterations and lung injury [7]. Previous studies showed that TLR4 signaling pathway played an important role in the
development of ALI and inhibition of TLR4 signaling pathway could prevent ALI induced by LPS [8]. Sesamin, a sesame lignan isolated from sesame seeds, has been reported to have many properties, such as antiinflammatory, anti-viral, and antioxidant activities. Sesamin has been reported to inhibit TNF-α and GRO-α production in LPS-stimulated THP-1 and human primary monocytes. Sesamin also inhibited LPS-induced proliferation and invasion in prostate cancer cells. Furthermore, sesamin has been reported to protect mice from lipopolysaccharide-/D-galactosamine-induced fulminant hepatic failure. However, the protective effects and anti-inflammatory mechanisms of sesamin on LPS-induced ALI remain unclear. Therefore, we investigated the protective effects and the underlying mechanisms of sesamin on LPS-induced ALI in mice.
Li Qiang and Jiang Yuan contributed equally to this work. 1
Emergency Department, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China 2 Department of Pulmonology, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China 3 To whom corresponden
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