Long non-coding RNA highly up-regulated in liver cancer protects tumor necrosis factor-alpha-induced inflammatory injury by down-regulation of microRNA-101 in ATDC5 cells

BackgroundOsteoarthritis (OA) is a familiar joint degenerative disease. Long non-coding RNAs (lncRNAs) play vital roles in the pathogenesis of OA. Nevertheless, the regulatory impacts of lncRNA highly up-regulated in liver cancer (lncRNA-HULC) on OA remain dimness. The study tried to probe the protective effect of HULC on ATDC5 cells against tumor necrosis factor-alpha (TNF-α)-induced inflammatory injury.MethodsRelative expression levels of pro-inflammatory cytokines (IL-6, IL-8 and MCP-1) and HULC in OA cartilage tissues and normal cartilage tissues were determined by RT-qPCR. TNF-α induced inflammatory injury model in ATDC5 cells was constructed, and the biological functions of HULC overexpression or suppression in TNF-α-injured ATDC5 cells were assessed. The relevancy between miR-101 and HULC was investigated by utilizing bioinformatics prediction, luciferase reporter assay, RNA pull-down and immunoprecipitation. MiR-101 mimic and inhibitor were transfected into ATDC5 cells, and its regulatory effect on TNF-α-injured ATDC5 cells was examined. Further, NF-κB and MAPK signaling pathways were finally detected by western blot.ResultsEnhancement of IL-6, IL-8 and MCP-1 were observated in OA cartilage tissues, but repression of HULC was discovered in OA cartilage tissues. HULC expression was decreased by TNF-α treatment, and overexpressed HULC significantly relieved TNF-α-induced ATDC5 cells injury. Additionally, miR-101 was mutual repressed with HULC, and overexpressed miR-101 reversed the protective effect of HULC in TNF-α-injured ATDC5 cells. Besides, HULC blocked NF-κB and MAPK pathways via repression of miR-101.ConclusionsThe discoveries testified that HULC protected ATDC5 cells against TNF-α-induced inflammatory injury by repression of miR-101.     

Notoginsenoside R1 up-regulates microRNA-132 to protect human lung fibroblast MRC-5 cells from lipopolysaccharide-caused injury

BackgroundPneumonia is a common lung disease in children with high fatality rate. Notoginsenoside R1 (NGR1) is the main active component extracted from the roots of Panax notoginseng (Burk.) F.H. Chen (Araliaceae). Here, we carefully explored the potential anti-inflammatory and protective effects of NGR1 on lipopolysaccharide (LPS)-induced lung fibroblast MRC-5 cell injury.MethodsViability and apoptosis of MRC-5 cells after different treatment or transfection were respectively assessed using CCK-8 assay and Annexin V-FITC/PI staining. The expression levels of microRNA-132 (miR-132), IL-1β, IL-6 and TNF-α in MRC-5 cells were measured using qRT-PCR. MicroRNA transfection was conducted to reduce the expression level of miR-132. Western blotting was used to analyze the protein expression levels of key factors involving in cell proliferation, apoptosis, NF-κB pathway and JNK pathway.ResultsLPS treatment caused MRC-5 cell proliferation inhibition, apoptosis and over-production of inflammatory cytokines. NGR1 treatment had no significant effects on MRC-5 cell proliferation, apoptosis and production of inflammatory cytokines, but protected MRC-5 cells from LPS-caused cell proliferation inhibition, apoptosis and over-production of inflammatory cytokines. In addition, NGR1 increased the expression level of miR-132 in MRC-5 cells. Knockdown of miR-132 reversed the protective effects of NGR1 on LPS-treated MRC-5 cells. Furthermore, NGR1 attenuated LPS-activated NF-κB and JNK pathways in MRC-5 cells via up-regulation of miR-132.ConclusionThis research confirmed the protective roles of NGR1 in lung fibroblast cell inflammatory injury. NGR1 protected MRC-5 cells from LPS-caused inflammatory injury through up-regulating miR-132 and then inactivating NF-κB and JNK pathways.     

circAtp9b knockdown alleviates LPS-caused inflammation provided that microRNA-27a is upregulated

BackgroundThe etiology of pneumonia is associated with gram-negative bacteria in malnourished children. To anatomize the molecular mechanisms, we focused on the modulatory function of circular RNA-Atp9b (circAtp9b) on inflammation in which microRNA-27a (miR-27a) might be implicated.MethodsMRC-5 cells were stimulated by lipopolysaccharide (LPS) to exhibit inflammatory lesions assessed by viability and apoptosis as well as the cleavage of caspase-3, production of interleukin-6 and tumor necrosis factor alpha, and generation of reactive oxygen species (ROS). circAtp9b and miR-27a were quantified by qRT-PCR. circAtp9b- or miR-27a-silenced MRC-5 cells were established to study their roles in inflammation. Moreover, the change of NF-κB and JNK pathways was monitored.ResultsLPS was observed to induce adverse inflammatory injuries by repressing viability and fortified apoptosis with cleavage of caspase-3, production of cytokines, formation of ROS and abundance of circAtp9b. The results suggested circAtp9b silence prevented MRC-5 cells from LPS-elicited insults, which was accompanied by blockage of NF-κB and JNK. circAtp9b silence restored miR-27a which was repressed by LPS. miR-27a knockdown abrogated the protective capacities of circAtp9b silence with activation of NF-κB and JNK in response to LPS.ConclusionLPS triggered adverse inflammation response by elevating the biogenesis of circAtp9b which caused a repressive role in miR-27a expression.     

Anti-inflammatory effect of tricin 4′-O-(threo-β-guaiacylglyceryl) ether,a novel flavonolignan compound isolated from Njavara on in RAW264.7 cells and in ear mice edema

Although recent study has shown tricin 4′-O-(threo-β-guaiacylglyceryl) ether (TTGE), an isolated compound from Njavara rice, to have the most potent anti-inflammatory effects, the action mechanism has not been fully understood. Here, we examined the effect of TTGE on the inflammation and elucidated the potential mechanism. We demonstrated that TTGE significantly inhibited LPS-induced NO and ROS generation in RAW264.7 cells, which was correlated with the down-regulating effect of TTGE on the iNOS and COX-2 expression via NF-κB and STAT3. TPA-induced ear edema was also efficiently inhibited by the TTGE treatment. TTGE blocked the induction of iNOS and COX-2 through the regulation of NF-κB and STAT3, which could explain the reduced TPA-induced edema symptoms. Moreover, the introduction of ERK inhibitor abrogated the anti-inflammatory effect of TTGE via the recovery of NF-κB and STAT3 signalings. Taken together, these results suggest that TTGE has anti-inflammatory properties through down-regulation of NF-κB and STAT3 pathways.     

Genistein promotes M1 macrophage apoptosis and reduces inflammatory response by disrupting miR-21/TIPE2 pathway

Cardiovascular diseases are a major cause of mortality, and vascular injury, a common pathological basis of cardiovascular disease, is deeply correlated with macrophage apoptosis and inflammatory response. Genistein, a type of phytoestrogen, exerts cardiovascular protective activities, but the underlying mechanism has not been fully elucidated. In this study, RAW264.7 cells were treated with genistein, lipopolysaccharide (LPS), nuclear factor-kappa B (NF-κB) inhibitor, and/or protein kinase B (AKT) agonist to determine the role of genistein in apoptosis and inflammation in LPS-stimulated cells. Simultaneously, high fat diet-fed C57BL/6 mice were administered genistein to evaluate the function of genistein on LPS-induced cardiovascular injury mouse model. Here, we demonstrated that LPS obviously increased apoptosis resistance and inflammatory response of macrophages by promoting miR-21 expression, and miR-21 downregulated tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) expression by targeting the coding region. Genistein reduced miR-21 expression by inhibiting NF-κB, then blocked toll-like receptor 4 (TLR4) pathway and AKT phosphorylation dependent on TIPE2, resulting in inhibition of LPS. Our research suggests that miR-21/TIPE2 pathway is involved in M1 macrophage apoptosis and inflammatory response, and genistein inhibits the progression of LPS-induced cardiovascular injury at the epigenetic level via regulating the promoter region of Vmp1 by NF-κB.     

Salidroside attenuates inflammatory response via suppressing JAK2-STAT3 pathway activation and preventing STAT3 transfer into nucleus

Salidroside (SAL) is an active ingredient isolated from the Rhodiola rosea, has potent anti-inflammatory effect, but the mechanism is still elusive. The purpose of this study is to verify the effects of SAL on LPS-induced inflammatory response and investigate the possible underlying molecular mechanism. RAW264.7 cells were pre-incubated with SAL for 2 h, then stimulated with or without LPS for another 16 h. The levels of TNF-α, MCP-1, IL-6, and PGE2 were detected by ELISA, and the production of NO was determined by nitrite analysis. The expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected by Western blotting. In RAW264.7 cells and murine peritoneal macrophages, the activation of signal molecules was also measured by Western blot. The nuclear translocation of STAT3 was determined by Laser confocal and nucleocytoplasmic separation experiments. Our results showed that SAL attenuated the productions of TNF-α, IL-6, MCP-1, PGE2 and NO dose dependently. SAL also suppressed LPS-induced expressions of iNOS and COX-2 significantly. Further studies revealed that SAL down-regulated the phosphorylation of JAK2-STAT3 signaling pathway and reduced the nuclear translocation of STAT3 induced by LPS in RAW264.7 cells and primary peritoneal macrophages. In addition, consistent with the results in vitro, in the model of mice acute lung injury (ALI) induced by LPS, SAL reduced the infiltration of inflammatory cells and decreased the levels of serum TNF-α and IL-6 obviously. Taken together, these data indicated that SAL exerted anti-inflammatory action via down-regulating LPS-induced activation of JAK2-STAT3 pathway and suppressing STAT3 transfer into the nucleus at least in part.     

2-Hydroxycircumdatin C inhibits LPS-induced BV2 cells inflammatory response via down-regulation of TLR4-mediated NF-κB/MAPK and JAK2/STAT3 pathways

2-Hydroxycircumdatin C (2-HCC) is a circumdatin-type alkaloid isolated from a coral-associated fungus Aspergillus ochraceus LZDX-32-15. In the present study, we aimed to assess the neuroprotective effects of 2-HCC on the microglia-mediated inflammatory response as well as underlining molecular mechanisms. 2-HCC could significantly down-regulate the overproduction of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induced by lipopolysaccharide (LPS) both in BV2 cells and primary microglial cells without affecting cell viability. In addition, 2-HCC exerted obvious neuroprotective effects against inflammatory injury in neurons when cocultured with LPS-induced microglia. Mechanism investigation indicated that the anti-inflammatory effect of 2-HCC involved the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) and alleviation of the LPS-induced TLR4-NF-κB/MAPK pathway. Furthermore, 2-HCC treatment attenuated LPS-induced activation of the JAK2/STAT3 pathway. In conclusion, these results indicated that the anti-inflammatory and neuroprotective properties of 2-HCC, at least partially, depended upon TLR4-NF-κB/MAPK and JAK2/STAT3 signaling pathways.     

Emodin suppresses LPS-induced inflammation in RAW264.7 cells through a PPARγ-dependent pathway

Inflammation is a defense and protective response to multiple harmful stimuli. Over and uncontrolled inflammation can lead to local tissues or even systemic damages and injuries. Actually, uncontrolled and self-amplified inflammation is the fundament of the pathogenesis of a variety of inflammatory diseases, including sepsis shock, acute lung injury and acute respiratory distress syndrome (ALI/ARDS). Our recent study showed that emodin, the main active component of Radix rhizoma Rhei, could significantly ameliorate LPS-induced ALI/ARDS in mice. However, its underlying signal pathway was not still very clear. Then, the aim of current study was to explore whether emodin could attenuate LPS-induced inflammation in RAW264.7 cells, and its involved potential mechanism. The mRNA and protein expression of ICAM-1, MCP-1 and PPARγ were measured by qRCR and western blotting, the production of TNF-α was evaluated by ELISA. Then, the phosphorylation of NF-κB p65 was also detected by western blotting. And NF-κB p65 DNA binding activity was analyzed by ELISA as well. Meanwhile, siRNA-PPARγ transfection was performed to knockdown PPARγ expression in cells. Our data revealed that LPS-induced the up-regulation of ICAM-1, MCP-1 and TNF-α, LPS-induced the down-regulation of PPARγ, and LPS-enhanced NF-κB p65 activation and DNA binding activity were substantially suppressed by emdoin in RAW264.7 cells. Furthermore, our data also figured out that these effects of emdoin were largely abrogated by siRNA-PPARγ transfection. Taken together, our results indicated that LPS-induced inflammation were potently compromised by emodin very likely through the PPARγ-dependent inactivation of NF-κB in RAW264.7 cells.     

Inhibition of miR-429 improves neurological recovery of traumatic brain injury mice and attenuates microglial neuroinflammation

BackgroundNeuroinflammation is a common therapeutic target for traumatic brain injury (TBI) due to its contribution to delayed secondary cell death and has the potential to occur for years after the initial insult. Previous studies demonstrate that miR-429 is up-regulated in the brain lesions of TBI mice, while its role in regulating neuroinflammation and brain injury remains largely unknown.MethodThe expression of miR-429 in LPS-activated microglia and microglia in TBI model was detected by RT-PCR. The effects of miR-429 inhibitors on LPS-activated microglia in vitro as well as neurological recovery and post-traumatic neuroinflammatory response in TBI model mice were detected in vivo.ResultsLPS and TBI significantly induce the up-expression of miR-429, inflammatory cytokines, MAPK-p38 and phosphorylated NF-κB in microglia, which were all inhibited by miR-429 inhibitors. Meanwhile, miR-429 inhibitors also attenuated the neurological impairment in TBI mice. Bioinformatics analysis showed that miR-429 could target and inhibit the expression of dual specificity protein phosphatase 1 (DUSP1), thus inhibiting the expression of MAPK-p38 and phosphorylated NF-κB.ConclusionmiR-429 plays a pro-inflammatory role in activated microglia by targeting DUSP1 signaling pathway. Inhibiting miR-429 can attenuate the inflammatory response of microglia and TBI-mediated brain damage.     

Dihydropyranoaurone compound damaurone D inhibits LPS-induced inflammation and liver injury by inhibiting NF-κB and MAPK signaling independent of AMPK

Recently, we reported the synthesis of damaurone D (DD), originally derived from Rosa damascene, and its anti-inflammatory effect in macrophages. Here, we investigated the molecular mechanism underlying the anti-inflammatory effect of DD in macrophages and further tested whether DD is protective against lipopolysaccharide (LPS)-induced liver injury. DD inhibited LPS-stimulated expression of pro-inflammatory genes and cytokine/chemokine secretion in a concentration-dependent manner in RAW 264.7 cells and thioglycolate-elicited mouse peritoneal macrophages. DD suppressed LPS-stimulated nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, as demonstrated by reduction in IκB kinase α/β phosphorylation, IκBα degradation, and levels of phosphorylated ERK, JNK, and p38 MAPK. The luciferase reporter activity of NF-κB and activator protein 1 was also attenuated by DD pretreatment. Furthermore, DD treatment induced AMP-activated protein kinase (AMPK) activation in cells and mouse liver, although the anti-inflammatory effect of DD was similar in dominant-negative AMPK-overexpressing cells. Lastly, DD-treated mice were protected against LPS-induced acute liver injury, based on morphologic and immunohistochemical observations; reduction in the plasma levels of aspartate aminotransferase, TNF-α, and MCP-1; and a decrease in inflammatory gene expression. In summary, our findings indicate that DD can protect against LPS-stimulated inflammation and liver injury at least partly by suppression of NF-κB and MAPK signaling pathways.     

Fraxin ameliorates lipopolysaccharide-induced acute lung injury in mice by inhibiting the NF-κB and NLRP3 signalling pathways

Fraxin, the effective component of the Chinese traditional medicine Cortex Fraxini, is reported to have anti-inflammatory effects. This study assessed the anti-inflammatory effect of fraxin on the lipopolysaccharide (LPS)-induced inflammatory response in A549 cells and the protective efficacy on LPS-induced acute lung injury (ALI) in mice. Fraxin reduced LPS-induced TNF-α, IL-6 and IL-1β production in A549 cells and alleviated the LPS-induced wet/dry (W/D) weight ratio and the effects observed via histopathological examination of the lung in vivo. Furthermore, fraxin reduced the protein concentrations in the broncho-alveolar lavage (BAL) fluid and cytokine production in the sera. Fraxin also clearly attenuated the oxidation index, including the activity of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH). Immunohistochemistry analysis showed that fraxin suppressed LPS-induced inflammatory damage. The expression of proteins involved in the NF-κB and NLRP3 inflammatory corpuscle signalling pathways was consistent between the lung tissues and cell samples. Overall, fraxin played a protective role in LPS-induced lung injury by inhibiting the NF-κB and NLRP3 signalling pathways.     

Isodeoxyelephantopin,a sesquiterpene lactone from Elephantopus scaber Linn., inhibits pro-inflammatory mediators’ production through both NF-κB and AP-1 pathways in LPS-activated macrophages

Isodeoxyelephantopin (IDET) has been identified as an anti-tumor natural constituent whose anti-tumor activity and mechanism have been widely investigated. Since the occurrence and development of cancer usually accompany with inflammation, and tumor signaling shares many components with inflammation signaling, the agents with anti-tumor activity are likely to possess anti-inflammation potential. Thus, the current study aims to demonstrate the anti-inflammatory activity along with the underlying mechanism of IDET in lipopolysaccharide (LPS)-primed macrophages. By using Griess method and ELISA, we found that in both bone marrow derived macrophages and alveolar macrophage cell line, IDET, at relatively low concentrations (0.75, 1.5 and 3 μM), could inhibit LPS-induced expression of various pro-inflammatory mediators including nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS), interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1) and IL-1β. Meanwhile, in activated MH-S cells, the inhibitory action of IDET on mRNA expression levels of these cytokines was also detected using qPCR. Mechanistically, the effects of IDET on two key inflammatory signalings, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) pathways, were determined in LPS-activated MH-S cells by reporter gene along with western blot assays. On the one hand, IDET suppressed NF-κB signaling via down-regulating phosphorylation and degradation of inhibitor of NF-κB (IκB)-α and the subsequent p65 translocation. On the other hand, IDET dampened AP-1 signaling through attenuating phosphorylation of both c-jun N-terminal kinase 1/2 (JNK1/2) and extracellular signal regulated kinase 1/2 (ERK1/2). Our study indicates that IDET might be a promising constituent from the anti-inflammatory herb Elephantopus scaber Linn. in mitigating inflammatory conditions, especially respiratory inflammation.     

GYF-17, a chloride substituted 2-(2-phenethyl)-chromone,suppresses LPS-induced inflammatory mediator production in RAW264.7 cells by inhibiting STAT1/3 and ERK1/2 signaling pathways

GYF-17, a 2-(2-phenethyl)-chromone derivative, was isolated from agarwood and showed superior activity of inhibiting NO production of RAW264.7 cells induced by LPS in our preliminary pharmacodynamic screening. In order to develop novel therapeutic drug for acute and chronic inflammatory disorders, the anti-inflammatory activity and underlying mechanism of GYF-17 were investigated in LPS-induced RAW264.7 cells. The results showed that GYF-17 could reduce LPS-induced expression of iNOS and then result in the decrement of NO production. More meaningful, the expression and secretion of key pro-inflammatory factors, including TNF-α, IL-6 and IL-1β, were intensively inhibited by GYF-17. Furthermore, GYF-17 also down regulated the expression of COX2 and the production of PGE2 which plays important role in causing algesthesia during inflammatory response. In mechanism study, GYF-17 selectively suppressed phosphorylation of STAT1/3 and ERK1/2 during the activation of NF-κB, MAPK and STAT signaling pathways induced by LPS. Collectively, GYF-17 can intensively suppress the production of LPS-induced inflammatory mediators in RAW264.7 cells by inhibiting STAT1/3 and ERK1/2 signaling pathways and thereby shows great potential to be developed into therapeutic drug for inflammatory diseases.     

Therapeutic effect of methyl salicylate 2-O-β-d-lactoside on LPS-induced acute lung injury by inhibiting TAK1/NF-kappaB phosphorylation and NLRP3 expression

Acute lung injury (ALI), characterized by pulmonary edema and inflammatory cell infiltration, is a common syndrome of acute hypoxemic respiratory failure. Methyl salicylate 2-O-β-d-lactoside (MSL), a natural derivative of salicylate extracted from Gaultheria yunnanensis (Franch.) Rehder, was reported to have potent anti-inflammatory effects on the progression of collagen or adjuvant-induced arthritis in vivo and in vitro. The aim of this study is to investigate the therapeutic effect of MSL on lipopolysaccharide (LPS)-induced acute lung injury and reveal underlying molecular mechanisms. Our results showed that MSL significantly ameliorated pulmonary edema and histological severities, and inhibited IL-6 and IL-1β production in LPS-induced ALI mice. MSL also reduced MPO activity in lung tissues and the number of inflammatory cells in BALF. Moreover, we found that MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation, as well as the expression of NLRP3 protein in lung tissues. Furthermore, MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation in Raw264.7 cells. In addition, MSL significantly inhibited nuclear translocation of NF-κB p65 in cells treated with LPS in vitro. Taken together, our results suggested that MSL exhibited a therapeutic effect on LPS-induced ALI by inhibiting TAK1/NF-κB phosphorylation and NLRP3 expression.     

ABIN-1 protects chondrocytes from lipopolysaccharide-induced inflammatory injury through the inactivation of NF-κB signalling

The A20-binding inhibitor of nuclear factor (NF)-κB-1 (ABIN-1) protein has recently been implicated as a key regulator of inflammation with involvement in multiple inflammatory diseases. However, the function of ABIN-1 in osteoarthritis (OA) remains unclear. In the current study, we explored the role of ABIN-1 in the regulation of lipopolysaccharide (LPS)-induced inflammatory injury of chondrocytes, which served as an in vitro model of OA. Results revealed that ABIN-1 expression was induced by chondrocyte exposure to LPS. ABN-1 silencing exacerbated LPS-induced apoptosis and the inflammatory response, while ABIN-1 overexpression alleviated the inflammatory response and LPS-induced apoptosis in chondrocytes. Moreover, ABIN-1 overexpression resulted in significantly decreased LPS-induced NF-κB activation. Notably, activation of NF-κB signalling significantly reversed ABIN-1-mediated inhibitory effects on LPS-induced inflammatory injury in chondrocytes. Taken together, these results demonstrate that ABIN-1 protects chondrocytes against LPS-induced inflammatory injury through the suppression of NF-κB signalling. Our study suggests a potential role for ABIN-1 in OA. Further, we show that ABIN-1 may serve as a potential target for controlling joint inflammation.     

Protective effect of aspirin-triggered resolvin D1 on hepatic ischemia/reperfusion injury in rats: The role of miR-146b

PurposeInflammatory responses play an important role in the tissue injury during liver ischemia/reperfusion (I/R). We previously reported that resolvin D1 (RvD1) administrated prior to hepatic I/R attenuates liver injury through inhibition of inflammatory response. In this study, we investigated the effects of the aspirin-triggered resolvin D1 (AT-RvD1) on hepatic I/R and the role of miR-146b in this process.MethodsPartial warm ischemia was performed in the left and middle hepatic lobes of Sprague-Dawley rats for 1 h, followed by 6 h of reperfusion. Rats received either AT-RvD1 (5 μg/kg), vehicle, or AT-RvD1 + miR-146b antagomir by intravenous injection 30 min before ischemia. Blood and tissue samples of the rats were collected after 6-h reperfusion.ResultsPretreatment with AT-RvD1 significantly diminished I/R-induced elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and significantly blunted the histological injury of the liver. Moreover, AT-RvD1 significantly inhibited inflammatory response, as indicated by attenuations of TNF-α and myeloperoxidase levels. Reduced apoptosis, and increased survival rate were observed in the AT-RvD1 group compared with the control I/R group. AT-RvD1 pretreatment increased miR-146b expression in the liver of the rats with hepatic I/R. Administration of miR-146b antagomir impaired the effects of AT-RvD1 on hepatic I/R injury in rats. Downregulation of miR-146b inhibited TRAF6 and NF-κB expression in liver.ConclusionsPre-administration of AT-RvD1 attenuates hepatic I/R injury partly through modulation of miR-146b.