• Molecules and Cells
• /
• v.25 no.2
• /
• pp.253-257
• /
• 2008

Acrolein is a highly electrophilic ${\alpha},{\beta}$-unsaturated aldehyde present in a number of environmental sources, especially cigarette smoke. It reacts strongly with the thiol groups of cysteine residues by Michael addition and has been reported to inhibit nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) activation by lipopolysaccharide (LPS). The mechanism by which it inhibits $NF-{\kappa}B$ is not clear. Toll-like receptors (TLRs) play a key role in sensing microbial components and inducing innate immune responses, and LPS-induced dimerization of TLR4 is required for activation of downstream signaling pathways. Thus, dimerization of TLR4 may be one of the first events involved in activating TLR4-mediated signaling pathways. Stimulation of TLR4 by LPS activates both myeloid differential factor 88 (MyD88)- and TIR domain-containing adapter inducing $IFN{\beta}$ (TRIF)-dependent signaling pathways leading to activation of $NF-{\kappa}B$ and IFN-regulatory factor 3 (IRF3). Acrolein inhibited $NF-{\kappa}B$ and IRF3 activation by LPS, but it did not inhibit $NF-{\kappa}B$ or IRF3 activation by MyD88, inhibitor ${\kappa}B$ kinase $(IKK){\beta}$, TRIF, or TNF-receptor-associated factor family member-associated $NF-{\kappa}B$ activator (TANK)-binding kinase 1 (TBK1). Acrolein inhibited LPS-induced dimerization of TLR4, which resulted in the down-regulation of $NF-{\kappa}B$ and IRF3 activation. These results suggest that activation of TLRs and subsequent immune/inflammatory responses induced by endogenous molecules or chronic infection can be modulated by certain chemicals with a structural motif that enables Michael addition.

• The Korean Journal of Food And Nutrition
• /
• v.30 no.2
• /
• pp.312-318
• /
• 2017

Aloe-emodin (AE) is the major bioactive component in aloe and known to exhibit anti-inflammatory activities. However, it has not been elucidated whether its anti-inflammatory potency can contribute to the elimination of obesity. The aim of the current study is to investigate the effect of AE on toll-like receptor 4 (TLR4) pathways in the presence of lipopolysaccharide (LPS) in 3T3-L1 adipocytes. 3T3-L1 adipocytes were treated with AE ($0-20{\mu}M$) for one hour, followed by LPS treatment for 30 min and then, adipokine mRNA expression levels were measured. Next, TLR4-related molecules were measured in LPS-stimulated 3T3-L1 adipocytes. AE significantly decreased the mRNA expression of the tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in a dose-dependent manner. Moreover, AE suppressed TLR4 mRNA expression. Further study showed that AE could suppress the nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) and phosphorylation of extracellular receptor-activated kinase (pERK). The results of this study suggest that AE directly inhibits $TLR4/NF-{\kappa}B/ERK$ signaling pathways and decreases the inflammatory response in adipocytes.

• Journal of the Korean Society of Food Culture
• /
• v.33 no.4
• /
• pp.337-344
• /
• 2018

Germinated brown rice (GBR, Orysa sartiva L.) has been reported to have anti-obesity and anti-inflammatory effects. However, the mechanisms underlying these effects in adipocytes are not fully understood. Therefore, this study was conducted to explore the anti-inflammatory mechanisms of GBR on lipopolysaccharide (LPS)-stimulated 3T3-L1 adipocytes. 3T3-L1 adipocytes were pretreated with GBR extracts (0-20 mg/mL) 1 h before LPS stimulation. The mRNA expression of adipokines and Toll-like receptor 4 (TLR4) were measured by RT-PCR. The protein expressions of TLR4-related molecules were detected by western blotting and nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) activation was measured. Our results showed that GBR extract dose-dependently inhibited mRNA expression of LPS-induced tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). GBR extract was found to inhibit LPS-induced mRNA expression of TLR4 and protein expression of both myeloid differentiation factor 88 (MyD88) and TNF receptor-associated factor 6 (TRAF6). Furthermore, GBR extract significantly inhibited extracellular receptor-activated kinase (ERK) phosphorylation and $NF-{\kappa}B$ activation. These results suggest that GBR extract has the anti-inflammatory effects on LPS-induced inflammation via inhibition of TLR4 signaling, includingthe ERK and $NF-{\kappa}B$ signaling pathways, in adipocytes.

• Journal of Ginseng Research
• /
• v.32 no.4
• /
• pp.315-323
• /
• 2008

In the previous studies, we isolated the compound K rich fractions (CKRF) and showed that CKRF inhibited Toll-like receptor (TLR) 4- or TLR9-induced inflammatory signaling. To extend our previous studies,1) we investigated the molecular mechanisms of CKRF in the TLR4-associated signaling via nuclear factor (NF)-${\kappa}B$, and in vivo role of CKRF for induction of tolerance in lipopolysaccharide (LPS)-induced septic shock. In murine bone marrow-dervied macrophages, CKRF significantly inhibited the induction of mRNA expression of proinflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, CKRF significantly attenuated the transcriptional activities of TLR4/LPS-induced NF-${\kappa}B$. Nuclear translocation of NF-${\kappa}B$ in response to LPS stimulation was significantly abrogated by pre-treatment with CKRF. Furthermore, CKRF inhibited the recruitment of p65 to the interferon-sensitive response element flanking region in response to LPS. Finally, oral administration of CKRF significantly protected mice from Gram-negative bacterial LPS-induced lethal shock and inhibited systemic inflammatory cytokine levels. Together, these results demonstrate that CKRF modulates the TLR4-dependent NF-${\kappa}B$ activation, and suggest a therapeutic role for Gram-negative septic shock.

• The Journal of Internal Korean Medicine
• /
• v.28 no.3
• /
• pp.442-452
• /
• 2007

Objectives : The purpose of this study was to investigate the toll-like receptor (TLR)-4 mediated anti-inflammatory effects of extract from Shigyungbanha-tang (SBT) on the peritoneal macrophage. Methods : To evaluate of TLR-4 mediated inflammatory of SBT. we examined NO and cytokine production in TRL-4 ligand (LPS : lipopolysaccharide) induced macrophages. Furthermore, we examined its molecular mechanism using western blot. Results : Extract from SBT itself does not have any cytotoxic effect in the peritoneal macrophages. Extract from SBT reduced LPS-induced nitric oxide (NO). tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin (IL)-6 and IL-12 production in peritoneal macrophages. SBT inhibited degradation of inhibitor kappa B-alpha ($I{\kappa}B-{\alpha}$) in the TLR-4 mediated peritoneal macrophages. Conclusions : These results suggest that SBT inhibits NO and cytokines production through inhibiting nuclear factor-kappaB (NF-${\kappa}$B) activation in peritoneal macrophage and that SBT may be beneficial oriental medicine for inflammation.

• Biomedical Science Letters
• /
• v.15 no.3
• /
• pp.257-260
• /
• 2009

Toll-like receptors (TLRs) recognize molecular structures derived from microbes including bacteria, viruses, yeast, and fungi. TLRs have emerged as a major signaling component of the mammalian host defense. TLR4 is a member of the Toll family that senses lipopolysaccharide (LPS), a cell wall component of gram negative bacteria. LPS recognition by TLR4 requires an additional accessory molecule, MD-2. LPS induces the activation of NF-${\kappa}B$ and IRF3 through MyD88 or TRIF-dependent pathways. The activation of NF-${\kappa}B$ leads to the induction of inflammatory gene products including cytokines and cyclooxygenase-2 (COX-2). This study was carried out to investigate the anti-inflammatory effects of oak wood vinegar. Oak wood vinegar inhibits the NF-${\kappa}B$ activation and COX-2 expression induced by LPS. These results provide new ideas to understand the mechanism of oak wood vinegar for its anti-bacterial and anti-inflammatory activities.

• Biomedical Science Letters
• /
• v.24 no.2
• /
• pp.102-107
• /
• 2018

Toll-like receptors (TLRs) play an important role for host defense against invading pathogens. The activation of TLRs signaling leads to the activation of $NF-{\kappa}B$ and the expression of pro-inflammatory gene products such as cytokines and inducible nitric oxide synthase (iNOS). To evaluate the therapeutic potential of cardamonin, which is a naturally occurring chalcone from Alpinia species (zingiberaceous plant species), $NF-{\kappa}B$ activation and iNOS expression induced by MALP-2 (TLR2 and TLR6 agonist) or LPS (TLR4 agonist) were examined. Cardamonin inhibited the activation of $NF-{\kappa}B$ induced by MALP-2 or LPS. Cardamonin also suppressed the iNOS expression induced by MALP-2 or LPS. These results suggest that cardamonin has the specific mechanism for anti-inflammatory responses by regulating of TLRs signaling pathway.

• The Korean Journal of Food And Nutrition
• /
• v.27 no.6
• /
• pp.1141-1146
• /
• 2014

The purpose of this study is to investigate the effects of arabinoxylan rice bran and endurance exercise training on TLR4 mediated protein expression in LPS-treated rats. The results showed that TLR4 as an important protein in the inflammatory response against lipopolysaccharide was shown to be significantly lower in both arabinoxylan supplement with exercise group and exercise group, thus the arabinoxylan rice bran had a higher inhibitory activity than arabinoxylan supplement group. However, $NF-{\kappa}B$ and MyD88 protein expression was not changed in arabinoxylan supplement with exercise training group, whereas $NF-{\kappa}B$ significantly decreased in 4 weeks of exercise training group. These results suggest that the supplement of arabinoxylan rice bran with exercise is likely to contribute to inflammation response and the arabinoxylan rice bran can be used as a possible safe alternative to the immunotherapeutic intervention.

• Biomedical Science Letters
• /
• v.19 no.2
• /
• pp.168-172
• /
• 2013

Toll-like receptors (TLRs) play an important role for host defense against invading pathogens. TLR4 has been identified as the receptor for lipopolysaccharide (LPS), which is a cell wall component of gram-negative bacteria. The activation of TLR4 signaling by LPS leads to the activation of NF-${\kappa}B$ and the expression of pro-inflammatory gene products such as cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). To evaluate the therapeutic potential of (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine (NVPP), previously synthesized in our laboratory, NF-${\kappa}B$ activation and iNOS and COX-2 expression induced by LPS were examined. NVPP inhibited the activation of NF-${\kappa}B$ induced by LPS. NVPP also suppressed the iNOS expression induced by LPS but it did not suppress COX-2 expression induced by LPS. These results suggest that NVPP has the specific mechanism for anti-inflammatory responses.

• Journal of Marine Bioscience and Biotechnology
• /
• v.12 no.1
• /
• pp.29-39
• /
• 2020

In this study, we investigated the inhibitory potential of an ethanol extract of Carpomitra costata (EECC) (Stackhouse) Batters, a brown alga, against neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results showed that EECC significantly suppressed the LPS-induced secretion of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E₂, with no significant cytotoxic effects. EECC also inhibited the LPS-induced expression of their regulatory enzymes, such as inducible NO synthase and cyclooxygenase-2. In addition, EECC downregulated the LPS-induced expression and production of the proinflammatory cytokines, tumor necrosis factor-α and interleukin-1β. In the mechanistic assessment of the antineuroinflammatory effects, EECC was found to inhibit the nuclear translocation and DNA binding of nuclear factor-kappa B (NF-κB) by disrupting the degradation of the κB-α inhibitor in the cytoplasm. Moreover, EECC effectively suppressed the enhanced expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88, as well as the binding of LPS to TLR4 in LPS-treated BV2 cells. Furthermore, EECC markedly reduced the LPS-induced generation of reactive oxygen species (ROS), demonstrating a strong antioxidative effect. Collectively, these results suggest that EECC repressed LPS-mediated inflammatory action in the BV2 microglia through the inactivation of NF-κB signaling by antagonizing TLR4 and/or preventing ROS accumulation. While further studies are needed to fully understand the anti-inflammatory effects associated with the antioxidant activity of EECC, the current findings suggest that EECC has a potential advantage in inhibiting the onset and treatment of neuroinflammatory diseases.