• Tuberculosis and Respiratory Diseases
• /
• v.54 no.5
• /
• pp.542-550
• /
• 2003

Background : Synthetic glucocorticoids are widely used in many chronic inflammatory diseases because of their excellent anti-inflammatory activity. Enhancing the transcription of $I{\kappa}B$ and preventing activated NF-${\kappa}B$ from binding to ${\kappa}B$ sites are thought to be the underlying mechanisms. But these data are largely derived from in vitro studies using cell lines. In this study, after administrating a steroid to volunteers, we evaluated the effect on the NF-${\kappa}B$ system. Methods : Prednisolone(0.5mg/kg/d) was orally administered to 5 healthy volunteers for 7 days. Before and after the administration, we sampled their peripheral blood monocytes, and performed western blot analysis both with stimulation, using IL-$1{\beta}$, LPS, TNF, and without stimulation(baseline). We also performed EMSA after stimulation with LPS. Results : After ingestion of the steroid, baseline expressions of $I{\kappa}B{\alpha}$ were increased in two of the subjects, while suppressed degradations of $I{\kappa}B{\alpha}$ to stimulations were observed in all five. In addition, the binding capacity of NF-${\kappa}B$ after the administration was decreased. Conclusion : Steroid plays such roles as enhancing the transcription of $I{\kappa}B{\alpha}$, suppressing the DNA binding capacity of NF-${\kappa}B$, and suppressing the degradation of $I{\kappa}B{\alpha}$.

• Food Science and Biotechnology
• /
• v.18 no.3
• /
• pp.813-817
• /
• 2009

The effect of 4 seaweed extracts (Desmarestia viridis, Dictyopteris divaricata, Scytosiphon lomentaria, and Ishige okamurae) on pro-inflammatory mediators as well as nuclear factor $(NF)-{\kappa}B$ in the stimulated Raw 264.7 cells was investigated. They reduced iNOS and interlukin $(IL)-1{\beta}$ expressions at transcription level. Of those, 3 extracts (D. divaricata, I. okamurae, and S. lomentaria) inhibited the COX-2 expression at translation level. $I{\kappa}B-{\alpha}$ degradation was inhibited by D. divaricata and S. lomentaria extracts. Therefore, we concluded that the extracts from D. divaricata and S. lomentaria could inhibit the activation of murine macrophage through the blocking of $NF-{\kappa}B$ activation.

• IMMUNE NETWORK
• /
• v.6 no.1
• /
• pp.27-32
• /
• 2006

Background: Chronic inflammation in the brain has known to be associated with the development of a various neurological diseases including dementia. In general, the characteristic of neuro-inflammation is the activated microglia over the brain where the pathogenesis occurs. Pro-inflammatory repertoires, interleukin-1${\beta}$ (IL-1${\beta}$) and nitric oxide (NO), are the main causes of neuro-degenerative disease, particularly in Alzheimer's disease (AD) which is caused by neuronal destruction. Those pro-inflammatory repertoires may lead the brain to chronic inflammatory status, and thus we hypothesized that chronic inflammation would be inhibited when pro-inflammatory repertoires are to be well controlled by inactivating the signal transduction associated with inflammation. Methods: In the present study, we examined whether biphenyl dimethyl dicarboxylate (DDB), an active compound from Schizandra chinensis Baillon, inhibits the NO production by a direct method using Griess reagent and by RT-PCR in the gene expression of inducible nitric oxide synthase (iNOS) and IL-1${\beta}$. Western blots were also used for the analysis of NF-${\kappa}B$ and I${\kappa}B$. Results: In the study, we found that DDB effectively inhibited IL-1${\beta}$ as well as NO production in BV-2 microglial cell, and the translocation of NF-${\kappa}B$ was comparably inhibited in the presence of DDB comparing those to the positive control, lipopolysaccharide. Conclusion: The data suggested that the DDB from Schizandra chinensis Baillon may play an effective role in inhibiting the pro-inflammatory repertoires which may cause neurodegeneration and the results imply that the compound suppresses a cue signal of the microglial activation which can induce the brain pathogenesis such as Alzheimer's disease.

• Herbal Formula Science
• /
• v.18 no.1
• /
• pp.105-120
• /
• 2010

Paeonia Suffruticosa and Prunus Persica have been used as oriental medicine for removal of fever, alleviation of pain, an anti-phlogistic effect and removal of extravasated blood. However, it has been never shown the effects of these herbal medicines on anti-inflammatory processes. This experiment was performed to show how these herbs could act as anti-inflammatory medicines at cellular level. Anti-inflammation effects of water extracts from Paeonia Suffruticosa and Prunus Persica as well as their mixture have been investigated, and the results were follows; 1) each extract slightly suppressed the expression and production of inflammatory mediators and enzymes such as NO, iNOS, IL-$1{\beta}$, and TNF-$\alpha$ in lipopolysaccharid(LPS)-stimulated RAW264.7 cells and mouse primary peritoneal macrophages in a dose-dependent manner. These suppressive effects, however, were synergistically increased by their mixture. 2) Each extract of Paeonia Suffruticosa and Prunus Persica insignificantly suppressed the activation and activity of NF-${\kappa}B$ in LPS-stimulated RAW264.7 cells, which controls the expression of inflammatory mediators such as NO, iNOS, IL-$1{\beta}$, and TNF-$\alpha$. However, extract mixture of Paeonia Suffruticosa and Prunus Persica suppressed effectively the activation and activity of NF-${\kappa}B$. 3) Each of Paeonia Suffruticosa and Prunus Persica induced translocation of NF-${\kappa}B$ to the nucleus from the cytosol and DNA-binding activity of nuclear NF-${\kappa}B$ in LPS-activated RAW264.7 cells. The extract mixture of Paeonia Suffruticosa and Prunus Persica showed more significant suppression of the NF-${\kappa}B$ translocation and its DNA-binding activity, as compared to those of the each extract. These results suggest that the extract mixture of Paeonia Suffruticosa and Prunus Persica may affect different control mechanisms for NF-${\kappa}B$ activation and the expression and production of NF-${\kappa}B$-dependent inflammatory mediators, indicating that this extract mixture may be useful for treatment of inflammatory diseases.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.22 no.4
• /
• pp.791-795
• /
• 2008

In the present study, Cordyceps sinensis extract (CSE) was evaluated to determine if it could protect pancreatic ${\beta}$ cells against cytokine-induced cytotoxicity of RINm5F cells. Treatment of cells with cytokines resulted in a decrease of viability, which was caused by increase of nitric oxide (NO) production. CSE protected cytokine-mediated viability reduction in a concentration-dependent manner. Incubation with CSE also induced a significant suppression of cytokine-induced inducible nitric oxide synthase (iNOS) protein and NO production. The molecular mechanism by which CSE inhibited iNOS protein expression appeared to involve the inhibition of $NF-{\kappa}B$ activation. The cytokine-stimulated RIN cells showed increases in $NF-{\kappa}B$ binding activity compared to unstimulated cells. However, pretreatment with CSE inhibited cytokines-induced $NF-{\kappa}B$ activation in RINm5F cells.

• Herbal Formula Science
• /
• v.18 no.1
• /
• pp.121-132
• /
• 2010

Inflammatory reaction is characterized by over-production of inflammatory mediators due to an up-regulation of inflammatory pathways, which produce pro-inflammatory mediators, such as interleukin-1beta (IL-$1{\beta}$), IL-6, tumour necrosis factor alpha (TNF-$\alpha$), prostaglantin $E_2$ ($PGE_2$), and nitric oxide (NO) in U937 cells. We investigate the anti-inflammatory effects of water extracts from Lonicerae Flos and Scutellariae Radix in lipopolysaccharide (LPS)-stimulated U937 cells. Each extract suppressed the production of inflammatory mediators (NO, IL-$1{\beta}$, TNF-$\alpha$, and $PGE_2$) and the expression of inducible NO synthase and cyclooxygenase-2 in LPS- stimulated U937 cells in a dose-dependent manner. These suppressive effects were synergistically increased by their combination. Their combination extract also inhibited NF-${\kappa}B$-DNA complex of NF-${\kappa}B$ binding activity and translocation of NF-${\kappa}B$ from cytosol to nucleus. These results suggest that the combination of water-extractable components of Lonicerae Flos and Scutellariae Radix may be useful for therapeutic drugs against inflammatory immune diseases, probably by suppressing the production of inflammatory mediators.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.4
• /
• pp.1165-1169
• /
• 2013

To elucidate the role of PKG isoforms in transcriptional control of cyclin D1, we employed a series of expression vectors of PKG $1{\alpha}$ and PKG $1{\beta}$ which encode HA-tagged wild type and constitutively active (SD and ${\Delta}N$) mutants. Our present study demonstrates that both the constitutively active mutants of PKG $1{\beta}$ downregulate the transcription of cyclin D1 when transiently transfected in NIH3T3 cells, whereas PKG $1{\alpha}$ mutants show weak inhibition. We further studied the transcriptional regulators of cyclin D1, such as, c-fos, NF-${\kappa}B$, and CRE by using the luciferase reporter assay. Constitutively active mutants of PKG $1{\beta}$ showed marked transcriptional downregulation of c-fos in NIH3T3 cells, whereas PKG $1{\alpha}$ downregulated c-fos to a lesser extent. We also found that the constitutively active mutants of PKG negatively regulated the activation of NF-${\kappa}B$ and CRE, suggesting their involvement in the regulation of cyclin D1.

• Biomolecules & Therapeutics
• /
• v.20 no.5
• /
• pp.457-462
• /
• 2012

The stem-bark of Kalopanax pictus (KP, family Araliaceae), of which main constituent is kalopanaxsaponin B, has been used for asthma, rhinitis, and arthritis in Chinese traditional medicine. To clarify anticolitic effect of KP, we examined anti-inflammatory effect of KP extract and kalopanaxsaponin B in lipopolysaccharide (LPS)-stimulated peritoneal macrophage and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitic mice. Of KP extracts, KP BuOH-soluble fraction most potently inhibited LPS-induced IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ expression, as well as NF-${\kappa}B$ activation. However, KP BuOH fraction increased IL-10, an anti-inflammatory cytokine. KP BuOH fraction also inhibited colon shortening and myeloperoxidase activity in TNBS-induced colitic mice. KP BuOH fraction also potently inhibited the expression of the pro-inflammatory cytokines, IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ as well as the activation of NF-${\kappa}B$. Kalopanaxsaponin B, a main constituent of KP, inhibited TNBS-induced colonic inflammation, including colon shortening, and TNBS-increased myeloperoxidase activity pro-inflammatory cytokine expression and NF-${\kappa}B$ activation in mice. Based on these findings, KP, particularly its main constituent, kalopanaxsaponin B, may ameliorate colitis by inhibiting NF-${\kappa}B$ pathway.

• Biomolecules & Therapeutics
• /
• v.22 no.4
• /
• pp.288-294
• /
• 2014

Mangostenone F (MF) is a natural xanthone isolated from Garcinia mangostana. However, little is known about the biological activities of MF. This study was designed to investigate the anti-inflammatory effect and underlying molecular mechanisms of MF in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. MF dose-dependently inhibited the production of NO, iNOS, and pro-inflammatory cytokines (TNF-${\alpha}$, IL-6, and IL-$1{\beta}$) in LPS-stimulated RAW264.7 macrophages. Moreover, MF decreased the NF-${\kappa}B$ luciferase activity and NF-${\kappa}B$ DNA binding capacity in LPS-stimulated RAW264.7 macrophages. Furthermore, MF suppressed the NF-${\kappa}B$ activation by inhibiting the degradation of $I{\kappa}B{\alpha}$ and nuclear translocation of p65 subunit of NF-${\kappa}B$. In addition, MF attenuated the AP-1 luciferase activity and phosphorylation of ERK, JNK, and p38 MAP kinases. Taken together, these results suggest that the anti-inflammatory effect of MF is associated with the suppression of NO production and iNOS expression through the down-regulation of NF-${\kappa}B$ activation and MAPK signaling pathway in LPS-stimulated RAW264.7 macrophages.

• Journal of Life Science
• /
• v.23 no.10
• /
• pp.1199-1208
• /
• 2013

Fibroblastic reticular cells (FRCs) form the structural backbone of the T zone provide a guidance path for immigrating T cells in the lymph node (LN). FRCs may contribute directly to developing T-cell biology in the LN and allow analyses of fundamental aspects of FRC biology related to T cells. FRCs inhibited T-cell apoptosis, and FRC culture supernatants strongly induced the expression of Bcl-xL in T cells against doxorubicin. Coculture of FRC and T cells resulted in rearrangements of the actin cytoskeleton, as well as global changes in the morphology of the FRCs. In addition, when cocultured, the T cells adhered to the FRC monolayer, and the membrane intercellular adhesion molecule (ICAM)-1 was slightly increased by day-dependent manner. In contrast, the expression of soluble ICAM-1 was dramatically increased in a day-dependent manner. Several chemokines, such as CCL5, CXCL1, CXCL5, CXCL16, CCL8, CXCL13, and ICAM-1, and MMPs were expressed in FRCs sensed by tumor necrosis factor (TNF) families. Nuclear factor kappa B ($NF{\kappa}B$)-RelA of the $NF{\kappa}B$ canonical pathway was translocated into FRC nuclear by $TNF{\alpha}$. In contrast, p52 proteolyzed from p100, a counterpart of RelB of the noncanonical $NF{\kappa}B$ pathway, accumulated in the peripheral FRC nucleus by agonistic anti-$LT{\beta}R$ antibody. In summary, we propose a model in which FRCs engage in bidirectional crosstalk to increase the efficiency of T-cell biology. This cooperative feedback loop may help to maintain tissue integrity and function during immune responses.