Schisandrin B Attenuates Inflammation in LPS-Induced Sepsis Through miR-17-5p Downregulating TLR4
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ORIGINAL ARTICLE
Schisandrin B Attenuates Inflammation in LPS-Induced Sepsis Through miR-17-5p Downregulating TLR4 Zhi-Rong Ji,1 Wei-Liang Xue,2,3 and Ling Zhang2
To investigate the mechanism of Schisandrin B (Sch B) on the inflammation in LPS-induced sepsis. Sepsis mouse model was established by injecting LPS. qRT-PCR and western blot were used to measure the expression of miR-17-5p and TLR4. ELISA was used to test the concentrations of IL-1β and TNF-α. Sch B could increase miR-17-5p expression, promote inflammation, and decrease TLR4 expression in sepsis mice and LPS-induced macrophages. Moreover, miR-17-5p could negatively regulate TLR4. Overexpression of miR-17-5p suppressed the concentrations of inflammatory factors (IL-1β and TNF-α) in LPS induced-macrophages, while pcDNA-TLR4 could change the inhibition effect. Additionally, miR-17-5p inhibitor changed the inhibitory effects of Sch B on TLR4 expression and the concentrations of IL-1β and TNF-α in LPS induced-macrophages. Sch B could attenuate inflammation in LPS-induced sepsis through miR-17-5p downregulating TLR4.
Abstract—
KEY WORDS: sepsis; Schisandrin B; miR-17-5p; TLR4; inflammation.
Toll-like receptor 4 (TLR4) is a member of TLR family, and its activation by lipopolysaccharide (LPS), a component of the cell wall of Gramnegative bacteria, is responsible for acute and chronic inflammatory disorders [4]. It has been reported that TLR4 exerts important functions in sepsis. For example, Venancio et al. [5] showed that CETP attenuated the inflammatory response in LPS-induced sepsis through reducing TLR4 expression. Therefore, modulation of TLR4 is a potential strategy to treat the inflammation in sepsis. Schisandrin B (Sch B) is a dibenzocyclooctadiene lignan isolated from Schisandra chinensis, a fruit of the Chinese magnolia vine [6]. The structure of Sch B is shown in Fig. 1a [7]. Sch B has been reported to exhibit antitumor, antioxidative, and anti-inflammatory properties. Previous in vitro and in vivo studies have demonstrated that Sch B can attenuate inflammation in hind limb I/R skeletal muscle injury through MAPK/NF-κB pathways in rats [8] and reduce inflammatory response induced by traumatic spinal cord injury via p53 signaling pathway
INTRODUCTION Sepsis is a systemic inflammatory syndrome caused by infection, which leads to multiple organ failures [1]. The mortality rate of patients with sepsis is very high [2]. It shows that excessive inflammatory response is one of its pathological characteristics [3]. However, there is no effective treatment for the inflammation in sepsis in clinic. Zhi-Rong Ji and Wei-Liang Xue contributed equally to this work, and they were co-first author. 1
Department of Traditional Chinese Medicine, People’s Hospital of Ningxia Hui Autonomous Region, the First Affiliated Hospital of Northwest University for Nationalities, Yinchuan, 750000, Ningxia, China 2 Department of Emergency, People’s Hospital of Ningxia Hui Autonomous Region, the First Affiliated Hospital of Northwest University for Nationalities, No.301 Zhengy
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