• Molecular & Cellular Toxicology
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• v.5 no.2
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• pp.141-146
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• 2009

Toll-like receptors (TLRs) induce innate immune responses by recognizing conserved microbial structural molecules. All TLR signaling pathways culminate in the activation of nuclear factor kappa-B (NF-$\kappa$B) leading to the induction of inflammatory gene products such as cyclooxygenase-2 (COX-2). Deregulated activation of TLRs can lead to the development of severe systemic inflammation. Divalent heavy metals, cadmium and mercury, have been used for thousands of years. While cadmium and mercury are clearly toxic to most mammalian organ systems, especially the immune system, their underlying toxic mechanism(s) remain unclear. Here, we report biochemical evidence that cadmium, but not mercury, inhibits NF-$\kappa$B activation and COX-2 expression induced by TLR2 or TLR4 agonists, while cadmium does not inhibit NF-$\kappa$B activation induced by the downstream signaling component of TLRs, MyD88. Thus, the target of cadmium to inhibit NF-$\kappa$B activation may be upstream of MyD88 including TLRs themselves, or events leading to TLR activation by agonists.

• Journal of Acupuncture Research
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• v.26 no.2
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• pp.31-40
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• 2009

Objectives: The purpose of this study is to investigate the effects of Daedon($LR_1$) Supplementation and Eumgok($KI_{10}$) Draining on changes of cerebral blood flow in normal rats. Methods : Regional cerebral blood flow(rCBF) and mean arterial blood pressure(MABP) in normal rats are observed, and those mechanisms were also investigated with pre-treatment of indomethacin (IDM) and methylene blue(MTB) each. Results : In this study, $LR_1$ supplementation and $KI_{10}$ draining elevated level of rCBF after 30 min, but MABP level was lowered at 30 min, then recovered toward normal level. Pre-treatment with indomethacin (IDM), an inhibitor of cyclooxygenase, inhibited increase of rCBF effectively, and pre-treatment with methylene blue(MTB), an inhibitor of guanylate cyclase, also inhibited increase of rCBF levels. On the other hand pre-treatment with IDM or MTB did not affect MABP levels. Conclusions : In conclusion, these results suggest that $LR_1$ supplementation and $KI_{10}$ draining can increase rCBF, and the mechanisms are thought to be related to both of cyclooxygenase and Guanylate cyclase pathways.

• The Korean Journal of Pain
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• v.31 no.3
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• pp.174-182
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• 2018

Background: The trigeminal nucleus caudalis (Vc) is a primary central site for trigeminal transmitting. Noxious stimulation of the trigeminal nociceptors alters the central synaptic releases and neural expression of some inflammatory and trophic agents. Orexin-A and the orexin 1 receptor (OX1R) are expressed in pain pathways including trigeminal pain transmission. However, the the mechanism(s) underling orexin-A effects on trigeminal pain modulation have not been fully clarified. Methods: Trigeminal pain was induced by subcutaneous injection of capsaicin in the upper lip in rats. The effect of trigeminal pain on cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) expression in the Vc of animals was determined by immunofluorescence. Subsequently, OX1R agonist (orexin-A) and antagonist (SB-334867-A) was administrated in the Vc to investigate the possible roles of the Vc OX1R on changes in COX-2 and BDNF levels following pain induction. Results: The data indicated an increase in COX-2 and decrease in BDNF immuno-reactivity in the Vc of capsaicin, and capsaicin- pretreated with SB-334867-A (80 nM), groups of rat. However, the effect of capsaicin on COX-2 and BDNF expressions was reversed by a Vc microinjection of orexin-A (100 pM). Conclusions: Overall, the present data reveals that orexin-A can attenuate capsaicin-induced trigeminal pain through the modulation of pain effects on COX-2 and BDNF expressions in the Vc of rats.

• Animal cells and systems
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• v.16 no.4
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• pp.274-279
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• 2012

Thymoquinone (TQ), a drug extracted from the black seeds of Nigella sativa, has been shown to exhibit anti-inflammatory, anti-oxidant, and anti-neoplastic effects in numerous cancer cells. The effects of TQ on cyclooxygenase-2 (COX-2) expression and prostaglandin $E_2$ ($PGE_2$) production in MDA-MB-231, however, remain poorly understood. Western blot analysis and immunofluorescence staining were performed to study the expression levels of inflammation regulatory proteins in MDA-MB-231. $PGE_2$ assay was conducted to explore the TQ-induced production of $PGE_2$. In this study, we investigated the effects of TQ on COX-2 expression and $PGE_2$ production in MDA-MB-231. TQ significantly induced COX-2 expression and increased $PGE_2$ production in a dose-dependent manner, as determined by a Western blot analysis and $PGE_2$ assay. Furthermore, the activation of Akt and p38 kinase, respectively, was up-regulated in TQ treated cells. Inhibition of p38 kinase with SB203580 and PI3kinase (PI3K) with LY294002 abolished TQ-caused COX-2 expression and decreased $PGE_2$ production. These results collectively demonstrate that TQ effectively modulates COX-2 expression and $PGE_2$ production via PI3K and p38 kinase pathways in the human breast cancer cell line MDA-MB-231.

• Fisheries and Aquatic Sciences
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• v.21 no.5
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• pp.14.1-14.8
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• 2018

The objective of this study was to investigate the anti-inflammatory effects of the pepsinolytic hydrolysate from the fish frame, Johnius belengerii, on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The J. belengerii frame hydrolysate (JFH) significantly suppressed nitric oxide (NO) secretion on LPS-stimulated RAW264.7 macrophages. Moreover, the JFH markedly inhibited the levels of protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, the LPS-stimulated mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 was downregulated when cells were cultured with the JFH. The JFH significantly reduced the phosphorylation of c-Jun N-terminal kinase (JNK) and the translocation of nuclear factor-kappa B ($NF-{\kappa}B$) in macrophages. As the result, the JFH has the potential anti-inflammatory activity via blocking the JNK and $NF-{\kappa}B$ signal pathways.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2022.09a
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• pp.108-108
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• 2022

Pine (Pinaceae family such as Pinus densiflora, P. rigida, and P.taeda) has been used as traditional medicine, its various parts (pine needle, bark, sap) have been used for hemostasis, bruises, and burns. These species were reported that have phenolics and flavonoids. We evaluated the anti-inflammation effects of PRT in lipopolysaccharide (LPS)-induced macrophages. These results showed that the ethyl acetate fraction of cone from Pinus rigida x P.taeda (ECRT) stabilized free radicals by reducing reactive oxygen species (ROS) and decreasing the production of nitric oxide (NO). ECRT decreased the expressions of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). In addition, ECRT significantly suppressed mRNA levels of inflammation-related factors such as cytokines, iNOS, and COX-2. As a result, ECRT was related to alleviating various pro-inflammatory mediators through IκB/NF-κB signaling pathways, including p65 translocation to the nucleus.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.144-144
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• 2002

Ceramide, formed by sphingomyelinase, is involved in the expression of cyclooxygenase-2 (COX-2). This study examines the effect of C2-ceramide (C2), a cell-permeable ceramide analog, on the LPS-inducible COX-2 expression and signaling pathways.(omitted)

• Biomolecules & Therapeutics
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• v.28 no.1
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• pp.104-109
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• 2020

Probenecid is a representative drug used in the treatment of gout. A recent study showed that probenecid effectively inhibits oxidative stress in neural cells. In the present study, we investigated whether probenecid can affect osteoclast formation through the inhibition of reactive oxygen species (ROS) formation in RAW264.7 cells. Lipopolysaccharide (LPS)-induced ROS levels were dose-dependently reduced by probenecid. Fluorescence microscopy analysis clearly showed that probenecid inhibits the generation of ROS. Western blot analysis indicated that probenecid affects two downstream signaling molecules of ROS, cyclooxygenase 2 (COX-2) and c-Jun N-terminal kinase (JNK). These results indicate that probenecid inhibits ROS generation and exerts antiosteoclastogenic activity by inhibiting the COX-2 and JNK pathways. These results suggest that probenecid could potentially be used as a therapeutic agent to prevent bone resorption.

• Biomolecules & Therapeutics
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• v.27 no.3
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• pp.241-253
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• 2019

Flavonoids are major plant constituents with numerous biological/pharmacological actions both in vitro and in vivo. Of these actions, their anti-inflammatory action is prominent. They can regulate transcription of many proinflammatory genes such as cyclooxygenase-2/inducible nitric oxide synthase and many cytokines/chemokines. Recent studies have demonstrated that certain flavonoid derivatives can affect pathways of inflammasome activation and autophagy. Certain flavonoids can also accelerate the resolution phase of inflammation, leading to avoiding chronic inflammatory stimuli. All these pharmacological actions with newly emerging activities render flavonoids to be potential therapeutics for chronic inflammatory disorders including arthritic inflammation, meta-inflammation, and inflammaging. Recent findings of flavonoids are summarized and future perspectives are presented in this review.

• Korean Journal of Food Science and Technology
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• v.41 no.2
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• pp.220-224
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• 2009

Toll-like receptors(TLRs) are pattern recognition receptors(PRRs) that recognize pathogen-associated molecular patterns(PAMPs) and regulate the activation of innate immunity. All TLR signaling pathways culminate in the activation of NF-${\kappa}$B, leading to the induction of inflammatory gene products such as COX-2. Licorice (Glycyrrhiza uralensis) has been used for centuries as an herbal medicine. Isoliquiritigenin(ILG), a simple chalcone-type flavonoid, is an active component present in licorice and has been used to treat many chronic diseases. However, the mechanism as to how ILG mediates health effects is still largely unknown. In the present report, we present biochemical evidence that ILG inhibits the NF-${\kappa}$B activation induced by TLR agonists and the overexpression of downstream signaling components of TLRs, MyD88, IKK${\beta}$, and p65. ILG also inhibits TLR agonists-induced COX-2 expression. These results suggest that anti-inflammatory effects of ILG are caused by modulation of the immune responses regulated by TLR signaling pathways.