• Journal of the Korean Society of Radiology
• /
• v.13 no.1
• /
• pp.133-140
• /
• 2019

Triglycerides (TG) are one of the triggers of chronic inflammatory lesions in the blood vessels. In the key factors in the development of inflammatory diseases, Pro-inflammatory cytokines such as tumor necrosis factor-alpha $(TNF-){\alpha}$ and interleukin-1 beta ($IL-1{\beta}$) contribute to the development of inflammatory lesions by recruiting other immune cells in the inflamed area or causing cell necrotic death. In this study, I investigated the effect of Jurkat T lymphocytes and U937 monocytes involved in vascular inflammation development on the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ on exposure to TGs. In Jurkat cells, mRNA expression of $TNF-{\alpha}$ is increased by exposure to TGs. However, the expression levels of $TNF-{\alpha}$ and $IL-1{\beta}$ were increased by TGs in U937 cells. To investigate whether inducible nitric oxide synthase (iNOS) is involved in the increase of expression of $TNF-{\alpha}$ and $IL-1{\beta}$ by TGs, treatment of W1400 (an iNOS inhibitor) resulted in recovery of expression level both $TNF-{\alpha}$ and $IL-1{\beta}$. Based on the present study, it was confirmed that the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ in monocytes and T lymphocytes. This increased cytokines contribute to development of vascular inflammatory lesions. In addition, iNOS is involved in the increase of $TNF-{\alpha}$ and $IL-1{\beta}$ expression by TGs.

• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.5
• /
• pp.283-287
• /
• 2003

While nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is beneficial for host survival, it is also detrimental to the host. Thus, regulation of iNOS gene expression may be an effective therapeutic strategy for the prevention of unwanted reactions at various pathologic conditions. During the screening process for the possible iNOS regulators, we observed that esculetin is a potent inhibitor of cytokine-induced iNOS expression. The treatment of 3T3-L1 adipocytes with the tumor necrosis factor-${\alpha}$ (TNF) induced iNOS expression, leading to enhanced NO production. TNF-induced NO production was inhibited by esculetin in a dose-dependent manner. Esculetin inhibited the TNF-induced NO production at the transcriptional level through suppression of iNOS mRNA and subsequent iNOS protein expression. These results suggest esculetin, a component of natural products, as a naturally occurring, nontoxic means to attenuate iNOS expression and NO-mediated cytotoxicity.

• Biomolecules & Therapeutics
• /
• v.19 no.4
• /
• pp.438-444
• /
• 2011

The mushroom Coriolus versicolor contains biologically active polysaccharides, most of which belong to the ${\beta}$-glucan group. Diverse physicochemical properties, due to different sources and isolated types of ${\beta}$-glucans, can induce distinct biological activities. We investigated the effects of ${\beta}$-glucans from C. versicolor on phagocytic activity, nitric oxide (NO), TNF-${\alpha}$ production, and signaling of dectin-1, a well-known ${\beta}$-glucan receptor, in macrophages. ${\beta}$-Glucans increased phagocytic activity and TNF-${\alpha}$ and NO-iNOS/eNOS production. Laminarin, a specific inhibitor of dectin-1, showed strong inhibitory effects on phagocytosis and subsequent TNF-${\alpha}$, iNOS, and eNOS production increased by ${\beta}$-glucans, indicating that ${\beta}$-glucans reacts with dectin-1 receptors. We examined whether the aforementioned cytokines were involved in the signaling pathway from the dectin-1 receptor to phagocytosis, and found that the inhibition of iNOS, eNOS, and TNF-${\alpha}$ receptors significantly decreased ${\beta}$-glucan-induced phagocytosis. In conclusion, our study showed that dectin-1 signaling, triggered by ${\beta}$-glucans, subsequently elicited TNF-${\alpha}$ and NO-iNOS/eNOS production, and that these molecules seem to act as secondary molecules that cause eventual phagocytosis by macrophages. These findings suggest that C. versicolor could be used as a nutritional medicine that may be useful in the treatment of infectious disease.

• The Korean Journal of Physiology and Pharmacology
• /
• v.1 no.5
• /
• pp.515-521
• /
• 1997

Endothelial cells play a central role in the inflammatory processes, and activation of nuclear factor kappa B ($NF-_{\kappa}B$) is a key component in that inflammatory processes. Previously, we reported that tumor necrosis factor alpha($TNF{\alpha}$) had protective effect of cell death induced by serum deprivation and this protection was related to $NF-_{\kappa}B$ activation. Inducible nitric oxide synthase (iNOS) is a member of the molecules which transcription is regulated mainly by $NF-_{\kappa}B$. And the role of nitric oxide (NO) generated by iNOS on cell viability is still controversial. To elucidate the mechanism of $TNF{\alpha}$ and $NF-_{\kappa}B$ activation on cell death protection, we investigate the effect of NO on the cell death induced by serum- deprivation in bovine cerebral endothelial cells in this study. Addition of $TNF{\alpha}$, which are inducer of iNOS, prevented serum-deprivation induced cell death. Increased expression of iNOS was confirmed indirectly by nitrite measurement. When selective iNOS inhibitors were treated, the protective effect of $TNF{\alpha}$ on cell death was partially blocked, suggesting that iNOS expression was involved in controlling cell death. Exogenously added NO substrate (L-arginine) and NO donors (sodium nitroprusside and S-nitroso-N-acetylpenicillamine) also inhibited the cell death induced by serum deprivation. These results suggest that NO has protective effect on bovine cerebral endothelial cell death induced by serum-deprivation and that iNOS is one of the possible target molecules by which $NF-_{\kappa}B$ exerts its cytoprotective effect.

• Journal of Periodontal and Implant Science
• /
• v.35 no.3
• /
• pp.799-811
• /
• 2005

This study was carried out to examine the potency of the three surface compo- nents from Porphyromonas gingivalis to stimulate the murine macrophage cell line RAW264.7 to synthesize the pro-inflammatory cytokine tumor necrosis factor alpha($TNF-{\alpha}$) and nitric oxide (NO). Lipopolysaccharide(LPS). lipid A-associated proteins(LAP) and saline-extractable surface -associated material(SAM) were isolated from P. gingivalis 381. $TNF-{\alpha}$ release into culture supernatants was determined by two-site ELISA. NO production was assayed by measuring the accumulation of nitrite in culture supernatants. Western blot analysis of iNOS and analysis of reverse transcription(RT)-PCR products were carried out. The surface components extracted from this bacterium were almost equally potent in stimulating release of $TNF-{\alpha}$ and NO by RAW264.7 cells. $TNF-{\alpha}$ that was being measured immunologically was due to activation of $TNF-{\alpha}$ gene transcription. The present study clearly shows that P. gingivalis surface components fully induced iNOS expression in RAW264.7 cells in the absence of other stimuli. The ability of P. gingivalis surface components to promote the production of $TNF-{\alpha}$ and NO may be important in the pathogenesis of inflammatory periodontal disease.

• YAKHAK HOEJI
• /
• v.48 no.2
• /
• pp.159-164
• /
• 2004

Primary pro-inflammatory cytokines are a trio: tumor necrosis- $\alpha$ (TNF-$\alpha$), interleukine-$\beta$ (IL-$\beta$), and interleukine-6 (IL-6). These cytokines initiate and regulate the acute-phase inflammatory response during infection, trauma, or stress and appear to play an important role in the immune process. Nitric oxide (NO) is a multi-functional mediator, which plays an important role in regulating various biological functions in vivo. NO production by inducible nitric oxide synthase (iNOS) in macrophages is essential for the defense mechanisms against microorganisms and tumor cells. However, over-expression of iNOS by various stimuli, resulting in over-production of NO, contributes to the pathogenesis of septic shock and some inflammatory and auto-immune disease. Solvent fractions of sage ( Salvia officinalis L.), which is cultivated in Jeju-Do, was assayed for their effects on TNF-$\alpha$ and IL-6 production in LPS-stimulated RAW 264.7 macrophages. Hexane and ethylacetate (EtOAc) fraction of sage inhibited the protein and mRNA expression of TNF-$\alpha$ and IL-6 in LPS stimulated RAW 264.7 cells at the concentration of 100 $\mu\textrm{g}$/$m\ell$. Also, incubation of RAW 264.7 cells with the fraction of hexane or EtOAc (50 $\mu\textrm{g}$/$m\ell$) inhibited the LPS induced nitrite accumulation and the LPS/IFN-${\gamma}$ induced iNOS protein. And this inhibition of iNOS protein is concordant with the inhibition of iNOS mRNA expression. Above results suggest that extract of sage may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines (TNF-$\alpha$, IL-1$\beta$, IL-6), iNOS and NO.

• The Korea Journal of Herbology
• /
• v.21 no.2
• /
• pp.135-142
• /
• 2006

Objectives : On-Bi-Tang(OB) has been prescribed Chinese traditional medicine for the treatment of inflammatory disease such as chronic renal failure. In this study, we investigated the anti-inflammatory effect of OB extract in the BV2 murine microglial cells. Methods : After the water extract of OB was treated in BV2 cells, murine microglial line, the cell viability was measured by MTT assay. The production of nitric oxide (NO) and $TNF-{\alpha}$ was determined based on Griess reagent and enzyme linked immunosorbant assay (ELISA). mRNA expression of inducible nitric oxide synthase (iNOS) and $TNF-{\alpha}$ was analyzed by RT-PCR. Results : OB extract significantly inhibited the LPS-induced production of NO and TNF-a in BV2 cells. OB extract also suppressed the mRNA expression of iNOS and $TNF-{\alpha}$ in BV2 cells activated with LPS. Conclusion : These data suggests that OB extract may have the anti-inflammatory effect through the modulation of NO production and inflammatory cytokine such as $TNF-{\alpha}$.

• Journal of Pharmacopuncture
• /
• v.6 no.2
• /
• pp.45-56
• /
• 2003

Objective : The purpose of this study was to investigate the effects of Bee Venom on the lipopolysaccharide(LPS), sodium nitroprusside(SNP), hydrogen peroxide$(H_2O_2)$-induced expression inducilble nitric oxide synthetase(iNOS), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) and nuclear factor kappa B(NF-kB) in RAW 264.7 cells, a murine macrophage cell line. Method : The expressions of expression iNOS and TNF-${\alpha}$ were determined by western blotting with corresponding antibodies. The expressions of expression NF-kB was assayed by EMSA method. Results : 1. The 0.5, 1 and $5{\mu}g/mg$ of bee venom on LPS-induced expression of iNOS, the $5{\mu}g/mg$ of bee venom on SNP-induced expression of iNOS and the $1{\mu}g/mg$ of bee venom on $H_2O_2$-induced expression of iNOS compared with control were inhibited significantly. 2. The 0.5, 1 and $5{\mu}g/mg$ of bee venom inhibited significantly LPS and $H_2O_2$-induced expression of TNF-${\alpha}$ compared with control, respectively. The $0.5{\mu}g/mg$ of bee venom increased significantly SNP-induced expression of TNF-${\alpha}$ compared with control. 3. The $5{\mu}g/mg$ of bee venom on LPS-induced expression of NF-kB, the $0.5{\mu}g/mg$ of bee venom on SNP-induced expression of NF-kB and the 0.5, $5{\mu}g/mg$ of bee venom on $H_2O_2$-induced expression of NF-kB were inhibited significantly compared with control, respectively.

• YAKHAK HOEJI
• /
• v.57 no.1
• /
• pp.70-75
• /
• 2013

The present study was designed to determine the effect of the Sandalwood Essential Oil (Santalum album) on pro-inflammatory factors such as NO, iNOS expression and IL-$1{\beta}$, IL-6, TNF-${\alpha}$ in lipopolysaccharide (LPS) - stimulated RAW264.7 macrophages cells. The cell toxicity was determined by MTS assay. To evaluate of anti-inflammatory effect of Sandalwood Essential Oil, amount of NO was measured using the NO detection kit and the iNOS expression was measured by western blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). And proinflammatory cytokines were measured by ELISA kit. As a result, Sandalwood Essential Oil reduced NO, iNOS expression and IL-$1{\beta}$, IL-6, TNF-${\alpha}$ production without cytotoxicity. Our results suggest that the Sandalwood Essential Oil may have an anti-inflammatory property through suppressing inflammatory mediator productions and appears to be useful as an anti-inflammatory oil.

• Journal of Korean Medicine Rehabilitation
• /
• v.23 no.2
• /
• pp.33-48
• /
• 2013

Objectives : Peripheral nerve injuries are commonly encountered clinical problems and often result in severe functional deficits. Sukjiyanggeun-Tang(shudiyangjin-tang), in oriental medicine, has been used to treat various musculoskeletal disorders. Methods : In the present study, the effects of aqueous extract of Sukjiyanggeun-Tang(shudiyangjin-tang) on functional recovery, severity of pain, and expressions of neurofilament, cycloxygenease-2(COX-2), inducible nitric oxide synthase(iNOS), and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) following sciatic crushed nerve injury in rats were investigated. For this study, walking tract analysis, plantar test, western blot analysis for COX-2 iNOS, and TNF-${\alpha}$, and Immunofluorescence test for neurofilament were performed. Results : In the present results, sciatic functional index(SFI) in walking tract analysis was significantly decreased following sciatic crushed nerve injury, and pain severity in plantar test was significantly increased. COX-2, iNOS and TNF-${\alpha}$ expressions were increased whereas neurofilament expression was decreased by sciatic crushed nerve injury, In contrast, treatment with Sukjiyanggeun-Tang(shudiyangjin-tang) improved SFI in walking tract analysis and suppressed the pain severity in sciatic crushed nerve injury. Sukjiyanggeun-Tang(shudiyangjin-tang) treatment also suppressed COX-2, iNOS, and TNF-${\alpha}$ expressions and enhanced the neurofilament expression in sciatic crushed nerve injury. Conclusions : In the present study, we have shown that Sukjiyanggeun-Tang(shudiyangjin-tang) is the effective therapeutic modality to ameliorate the symptoms of sciatic crushed nerve injury.