• Archives of Pharmacal Research
• /
• v.26 no.12
• /
• pp.1067-1073
• /
• 2003

Ursodeoxycholic acid (UDCA) is a non-toxic, hydrophilic bile acid in widespread clinical use mainly for acute and chronic liver disease. Recently, treatment with UDCA in hepatic graft-versus-host disease has been given in immunosuppressive therapy for improvement of the biochemical markers of cholestasis. Moreover, it has been reported that UDCA possesses immunomodulatory effects by the suppression of cytokine production. In the present study, we hypothesized that UDCA may inhibit the production of the pro-inflammatory cytokine, IL-1$\beta$, and nitric oxide (NO) in microglia. In the study, we found that 100 $\mu$ g/mL UDCA effectively inhibited these two pro-inflammatory factors at 24 hand 48 h, compared to the $A\beta$42-pretreated groups. These results were compared with the LPS+UDCA group to confirm the UDCA effect. As microglia can be activated by several stimulants, such as $A\beta$42, in Alzheimers brain and can release those inflammatory factors, the ability to inhibit or at least decrease the production of IL-1$\beta$ and NO in Alzheimers disease (AD) is essential. Using RT-PCR, ELISA and the Griess Reagent System, we therefore found that UDCA in $A\beta$42 pre-treated cultures played a significant role in suppressing the expression or the production of IL-1$\beta$ and NO. Similarly, lipopolysaccharide (LPS) did not activate microglia in the presence of UDCA. Moreover, we found that UDCA exhibits a prolonged effect on microglial cells (up to 48 h), which suggests that UDCA may play an important role in chronic cell damage due to this long effect. These results further imply that UDCA could be an important cue in suppressing the microglial activation stimulated by massive AD peptides in the AD progressing brain.

• Tuberculosis and Respiratory Diseases
• /
• v.71 no.3
• /
• pp.172-179
• /
• 2011

Background: Statins can regulate the production of pro-inflammatory cytokines and inhibit MMP production or activation in a variety of types of cells. This study evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodeling processes. Methods: This study, using an in-vitro model (three-dimensional collagen gel contraction system), evaluated the effect of cytokines (tumor necrosis factor-${\alpha}$, TNF-a and interleukin-$1{\beta}$, IL-1b) on the MMP release and MMP activation from human lung fibroblasts. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. Results: In three-dimensional collagen gel cultures (3D cultures) where cytokines (TNF-a and IL-1b) can induce the production of MMPs by fibroblasts, it was found that simvastatin inhibited MMP release. In 3D cultures, cytokines together with NE induced collagen degradation and can lead to activation of the MMP, which was inhibited by simvastatin. Conclusion: Simvastatin may play a role in regulating human lung fibroblast functions in repair and remodeling processes by inhibiting MMP release and the conversion from the latent to the active form of MMP.

• Polymer(Korea)
• /
• v.36 no.1
• /
• pp.1-8
• /
• 2012

In this study, we employed hydroxypropyl-${\beta}$-cyclodextrin (HP-${\beta}$-CD) as an excipient to produce poly(lactic-$co$-glycolic acid) (PLGA) fine particles by a supercritical fluid process, called aerosol solvent extraction system (ASES), and investigated the effect of HP-${\beta}$-CD content on the morphology of the particles. The influence of HP-${\beta}$-CD on the drug release characteristics of paclitaxel-loaded PLGA particles was also evaluated. Fine particles were obtained when the HP-${\beta}$-CD content in PLGA/HP-${\beta}$-CD mixtures was greater than 40% and 30%, respectively, for PLGA(75:25) and PLGA(50:50), whereas a film-like precipitate was obtained for lower HP-${\beta}$-CD content. The release rate for paclitaxel loaded PLGA(75:25)/HP-${\beta}$-CD particles was found to increase with HP-${\beta}$-CD content.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.1
• /
• pp.71-76
• /
• 2015

Magnesium sulfate is widely used as a food additive and as an orally administered medication. The aim of this study was to evaluate the possible cytotoxicity of magnesium sulfate on AGS human gastric adenocarcinoma cells and gastric mucosa in mice. A trypan blue exclusion assay was used to determine the reduction in viability of AGS cells exposed to magnesium sulfate, and then effects on cell proliferation were quantified. The role of magnesium sulfate-mediated pro-inflammatory cytokine production in AGS cells was also investigated. mRNA expression for IL-$1{\beta}$, IL-6, IL-8, and TNF-${\alpha}$ was determined by RT-PCR, and secretion of these cytokines was measured by ELISA. Immunohistochemical evaluation of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ expression was conducted in mouse gastric mucosa. Addition of 3 to 50 mM magnesium sulfate to AGS cells inhibited both cell proliferation and cell viability in a dose-dependent manner. Magnesium sulfate had little effect on production of IL-$1{\beta}$ or IL-6 but significantly inhibited production of IL-8. The animal model demonstrated that magnesium sulfate induced production of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$. These preliminary data suggest that magnesium sulfate had a direct effect on the stomach and initiates cytotoxicity in moderate concentrations and time periods by inhibiting viability a nd proliferation of AGS cells and by regulating expression and/or release of pro-inflammatory cytokines.

• Journal of Periodontal and Implant Science
• /
• v.27 no.2
• /
• pp.425-441
• /
• 1997

The neuropeptide substance P(SP) has been implicated in the mediation of inflammation and immune-mediated disease such as arthritis. Recently, it was reported that SP was markedly increased around the blood vessels in inflamed gingiva as well as in close association with the inflammatory cell infiltrate. These results support that SP may contribute to the pathophysiology of neuronal inflammation in human periodontal tissues. SP may regulate inflammatory/immune responses by stimulating the proliferation of human T cells, differentiation and antibody-secreting potential of B cells, macrophage respiratory burst, connective tissue proliferation, and the secretion of cytokines from monocytes and T cells. Here, I studied potential role of SP as a costimulatory chemical signal in inflammatory/immune responses, by determining the released proinflammatory cytokines such as $MIP-1{\alpha}$, $IL-1{\beta}$, and IL-6 from culture supernatants of homogeneous immune cell lines. Serum free cell supernatants were concentrated with TCA precipitation, fractionated with SDS-PAGE, and subjected into western blot analysis. Among 15 cell lines tested, macrophage/monocyte cell line RAW264.7 and WRl9m.1 showed the highest level of induction of $MIP-1{\alpha}$ when stimulated with LPS. Discrete IL-6 bands with multiple forms of molecular mass were detected from supernatants of B cell lines A20(32kDa), Daudi(32, 35kDa), and SKW6.4(29kDa), which were expressed constitutively. $IL-1{\beta}$ could not be detected by the method of western blot analysis from supernatants of all cell lines tested except RAW264.7, WRl9m.1, and erythroid cell line K562 which showed the least amount of $IL-{\beta}$ secretion. SP $10^{-9}M$ with suboptimal dose of LPS treatment showed synergistic induction of $MIP-1{\alpha}$ release from RAW264.7 or WR19m.1, and also IL-6 release from A20, but this synergism is not the case in costimulation of RAW264.7 or WRl9m.1 with SP $10^{-9}M$ and TPA. Although treatment of T cell line CTLL-R8 with SP $10^{-7}M$ or PHA+TPA induced modest level of $MIP-1{\alpha}$ secretion, synergism was not observed when they are applied together. These findings all together suggest the possibility of a regulatory role of SP in inflammatory/immune reaction through differential modulation of bioactivities of other chemical cosignals.

• Journal of Chitin and Chitosan
• /
• v.23 no.4
• /
• pp.277-284
• /
• 2018

In this study, we investigated the anti-allergic effect of the ethyl acetate fraction of Ecklonia cava (EC-EtoAc) on the immunoglobulin E (IgE)/bovine serum albumin (BSA)-mediated activation of bone marrow-derived cultured mast cells (BMCMCs). We revealed that the $62.5{\mu}g/ml$ of EC-fractions ($EC-CHCl_3$, EC-Hexane and EC-EtoAc) inhibited IgE/BSA-activated ${\beta}$-hexosaminidase release from BMCMCs without cytotoxicity. Especially, EC-EtoAc showed the higher ${\beta}$-hexosaminidase release than the others. Also, EC-EtoAc reduced the expression levels of cytokines such as interleukin (IL)-$1{\beta}$, IL-4, IL-5, IL-6, IL-10, IL-13, interferon (IFN)-${\gamma}$ and tumor necrosis factor (TNF)-${\alpha}$ and a chemokine, thymus- and activation-regulated chemokine (TARC), compared to the only IgE/BSA-treated BMCMCs. Furthermore, EC-EtoAc significantly prevented the binding of IgE to Fc epsilon receptor $(Fc{\varepsilon}R)I$ and reduced the $Fc{\varepsilon}RI$ expression on the sensitized BMCMCs. Taken together, these results suggest that E. cava may be the natural agent with beneficial potentials for the treatment of type I allergic diseases induced by mast cell activation.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.26 no.6
• /
• pp.915-921
• /
• 2012

Artemisiae Asiaticae Herba (AAH) has been used to remedy of symptoms such as bleeding, dysmenorrhea, eczema and itchy skin in Oriental Medicine. In this study, we investigated the protective effect of AAH on allergic response. The effect of AAH was analyzed by ELISA and RT-PCR in RBL-2H3 cells. We investigated cell viability, ${\beta}$-hexosaminidase and histamine as markers of degranulation, production of IL-4 and TNF-${\alpha}$, and gene expression of HDC2, cytokines and $Fc{\varepsilon}RI$ ${\alpha}{\beta}{\gamma}$ subunit. We found that AAH suppressed ${\beta}$-hexosaminidase and histamine release, the production of IL-4 and TNF-${\alpha}$ in RBL-2H3 by the anti-DNP IgE plus DNP-HSA stimulation. AAH also significantly decreased cytokine mRNA expressions, such as IL-$1{\beta}$, IL-2, IL-3, IL-4, IL-5, IL-6, IL-12, IL-13, TNF-${\alpha}$, and GM-CSF, and increased cytokine mRNA expressions of IL-10 in RBL-2H3. In addition, AAH suppressed mRNA expression of $Fc{\varepsilon}RI$ ${\alpha}{\beta}{\gamma}$ subunit on cell surface. Our results indicate that AAH protects against allergic response and exerts an anti-inflammatory effect through the inhibition of degranulation and production of cytokines and expression of $Fc{\varepsilon}RI$ ${\alpha}{\beta}{\gamma}$ subunit.

• The Journal of Internal Korean Medicine
• /
• v.43 no.1
• /
• pp.68-78
• /
• 2022

Objective: In this study, we investigated the protective effect of rhododendron mucronulatum extract (RME) on allergic reactions and inflammation. Methods: The effect of RME was determined using ELISA and RT-PCR in RBL-2H3 mast cells and RAW 264.7 macrophage cells. We determined cell viability, β-hexosaminidase release, and the synthesis of IL-4 and TNF-α in RBL-2H3 cells. In addition, we determined NO from RAW 264.7 and the gene expression of IL-1β, iNOS, IL-6, TNF-α, and IL-10. Results: RME inhibited β-hexosaminidase release and synthesis of IL-4 and TNF-α in RBL-2H3 by the anti-DNP IgE plus DNP-HSA stimulation. In addition, RME inhibited the production of NO and the gene expression of IL-1β, iNOS, IL-6, and TNF-α in LPS-stimulated RAW 264.7 cells. Conclusion: From these results, we concluded that RME possesses anti-allergic activity and anti-inflammatory activity due to the inhibition of mast cells and macrophage function.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.20 no.1 s.32
• /
• pp.38-50
• /
• 2007

Object : We investigated the effect of Gamiokyaek-tang(GOYT) on immediate type hypersensitivity. Methods : We investigated anti-dinitrophenyl(DNP) IgE-mediated passive cutaneous anaphylaxis(PCA) and acetic acid-induced vascular permeability in rodents. Also we measured MTT assay, ${\beta}-hexosminidase$ activity and IL-4 from RBL-2H3 and nitric oxide from Raw264.7. Results : GOYT inhibited passive cutaneous anaphylaxis and acetic acid-induced vascular permeability by oral administration. All the concentrations of GOYT from 0.1 to 5mg/ml didn't have an effect on cell viability and cytotoxicity. In RBL-2H3, ${\beta}-hexosminidase$ release and IL-4 production were significantly reduced by 1, 2 and 5mg/ml of GOYT. In Raw264.7, nitric oxide level was decreased by 5mg/ml of GOYT. Conclusion : These results indicate that GOYT have inhibition effects on immediate type hypersensitivity.

• The Journal of Internal Korean Medicine
• /
• v.28 no.2
• /
• pp.304-320
• /
• 2007

Objective : To evaluate the effect of Astragalus Membranaceus Extrac (AME) on myelosuppression, activity and immune modulation in 5-fluorouracil (5-FU) treated mice. Method : We carried out complete blood count, histological analysis of bone marrow, and cell colony forming assay for hematopoietic progenitor to evaluate the effect of AME on myelosuppression and conducted swimming test, survival rate, nitric oxide (NO) assay, 51Cr release assay in natural killer cell, mRNA expression of $IL-1{\beta}$, IL-2, IL-4, IL-6, IL-10, $TNF-{\alpht}$, $IFN-{\gamma}$, $TGF-{\beta}$ and GM-CSF in spleen cells to evaluate the effect of AME on quality of life (QOL). Results : AME improved 5-FU induced myelosuppression and peripheral blood count was recovered effectively, had significant efficacy to protect against chemotherapy induced marrow-destruction and on hematopoiesis compared with the control group, improved increase survival rate and the swimming time, had a stimulatory effect on macrophage activation and NK cell activity, and up-regulated cytokine gene transcription (IL-2, IL-6, $IFN-{\gamma}$) in murine immunologic system. Conclusion : We can conclude that AM is an effective herbal agent for improvement of myelosuppression and QOL in 5-FU treated mice.