• IMMUNE NETWORK
• /
• v.21 no.6
• /
• pp.42.1-42.20
• /
• 2021

Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

• 한국유가공학회:학술대회논문집
• /
• 2007.09a
• /
• pp.49-58
• /
• 2007

Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.44 no.3
• /
• pp.249-258
• /
• 2018

Airborne pollution causes oxidative damage, inflammation, and premature aging of skin. Resveratrol is a polyphenol compound that has various biological activities such as antioxidant, anti-inflammation, and anti-melanogenic activities but it is unstable to heat and light. Resveratryl triacetate (RTA) is a new cosmetic ingredient that is more stable than resveratrol and its skin safety and whitening efficacy have been reported previously. The purpose of this study was to examine the effects of resveratrol and resveratryl triacetate (RTA) on the inflammatory responses of human epidermal keratinocytes (HEKs) exposed to airborne particulate matters with a diameter of < $10{\mu}m$ (PM10). Cultured HEKs were exposed to PM10 in the absence or presence of resveratrol and RTA. Assays were undertaken to determine cell viability, the production of reactive oxygen species (ROS), and the expression of inflammatory cytokines. PM10 treatment decreased cell viability, and increased the expression of pro-inflammatory cytokines such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6), and interleukin-8 (IL-8). Resveratrol and RTA reduced cell death and ROS production induced by PM10. PM10-induced mRNA expression of the inflammatory cytokines was either attenuated (IL-6), or enhanced ($IL-1{\beta}$), or unaffected ($TNF-{\alpha}$ and IL-8) by resveratrol and RTA. PM10-induced IL-6 protein expression was attenuated by resveratrol and RTA. This study suggests that resveratrol and RTA have activities regulating cell damage and inflammatory responses of the skin exposed to airborne particulate matters.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.44 no.11
• /
• pp.1612-1620
• /
• 2015

Inflammation is a complex process involving a variety of immune cells, which defend the body from harmful stimuli. However, pro-inflammatory cytokines and inflammatory mediators can also exacerbate diseases such as cancer. Onion peel contains several phenolic compounds, including quercetin at an amount 20 times greater in peel than edible flesh. Therefore, in this study, the anti-inflammatory effects of onion peel ethanol extract (OPEE) were investigated lipopolysaccharide-induced inflammatory response. In our results, NO production decreased in a dose-dependent manner. Secretion of IL-6, $TNF-{\alpha}$, and $IL-1{\beta}$ was suppressed by 44%, 53%, and 60% respectively, at $100{\mu}g/mL$. Moreover, OPEE also suppressed expression of COX-2, iNOS, $NF-{\kappa}B$, and MAPKs in a dose-dependent manner. Formation of mice ear edema was reduced at the highest dose tested compared to the control, and reduction of ear thickness was observed in the histological analysis as well. In the acute toxicity test, no morality was observed in mice administered 5,000 mg/kg body weight of OPEE over a 2-week observation period. These results suggest that OPEE may have significant effects on inflammatory factors and be a potential anti-inflammatory material.

• Journal of Life Science
• /
• v.28 no.2
• /
• pp.207-215
• /
• 2018

Inflammatory response and oxidative stress play critical roles in the development and progression of many human diseases. Therefore, a great deal of attention has been focused on finding functional materials that can control inflammation and oxidative stress simultaneously. The purpose of this study was to investigate the effects of Socheongja and Socheong 2, Korean black seed coat soybean varieties, on the inflammatory and oxidative stress induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages. Our data indicated that the extracts of Socheongja (SCJ) and Socheong 2 (SC2) significantly suppressed LPS-induced production of nitrite oxide (NO) and prostaglandin $E_2$, key pro-inflammatory mediators, by suppressing the expression of inducible NO synthase and cyclooxygenase-2. It was also found that SCJ and SC2 reduced the LPS-induced secretion of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$, which was concomitant with a decrease in the protein levels. In addition, SCJ and SC2 markedly diminished LPS-stimulated intracellular reactive oxygen species accumulation, and effectively enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1 expression. Furthermore, LPS-induced activation of mitogen-activated protein kinases (MAPKs) was abrogated by SCJ and SC2. Taken together, these data suggest that SCJ and SC2 may offer protective roles against LPS-induced inflammatory and oxidative responses in RAW 264.7 macrophages through attenuating MAPKs pathway, and these effects are mediated, at least in part, through activating Nrf2/HO-1 pathway. Given these results, we propose that SCJ and SC2 have therapeutic potential in the treatment of inflammatory and oxidative disorders caused by over-activation of macrophages.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.22 no.2
• /
• pp.1-18
• /
• 2009

Objective : Moutan Cortex (the root bark of Paeonia suffruticosa Andr.) is widely used in oriental medicine as a remedy for inflammation. However, as yet there is no clear explanation of how MC(Moutan Cortex) affects the production of inflammatory cytokine. This study was to determine the effects of Essence extracted MC on the mast cell-mediated inflammatory responses. Method : We observed the effect of MC on compound 48/80-induced histamine release of rat peritoneal mast cells and the effect of administering MC on PCA in rat. We measured the amount of inflammatory cytokine production induced by the phorbol myristate acetate (PMA) plus calcium ionophore(A23187) in the human mast cell line (HMC-1) incubated with various concentrations of MC. The TNF-$\alpha$ protein levels were analysised by Western blot. The TNF-$\alpha$, IL-6 and IL-8 secreted protein levels were measured by the ELISA assay. The TNF-$\alpha$, IL-6 and IL-8 mRNA levels were measured by the RT-PCR analysis. NF-$\kappa$B, phospho-I$\kappa$B and MAPKs were exmined by Western blot analysis. The NF-$\kappa$B promoter activity was examined by luciferase assay. Result : 1. Enzyme immunoassay indicated that MC suppressed histamine secretion of rat peritoneal mast cells. 2. In PCA dependent on IgE, MC had anti-allergic effect of the internal surface of rat skin. 3. Western blot indicated that MC decreased TNF-$\alpha$ protein levels. 4. ELISA indicated that MC decreased TNF-$\alpha$, IL-6 but MC had no significant effect on IL-8 in HMC-1 cells. 5. RT-PCR indicated that MC decreased TNF-$\alpha$, IL-8 but MC had no significant effect on IL-6 in HMC-l cells. 6. Western blot indicated that MC suppressed the induction of MAPKs, NF-$\kappa$B & phospho-I$\kappa$B activity in HMC-1 cells. 7. Luciferase assay indicated that MC suppressed the PMA plus A23187-induced NF-$\kappa$B promoting activityin HMC-1 cells. Conclusion : In this study, we have found that MC is an inhibitor of NF-$\kappa$B, MAPKs & cytokines on the mast cell-mediated inflammatory responses.

• Parasites, Hosts and Diseases
• /
• v.55 no.3
• /
• pp.295-304
• /
• 2017

Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF-, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-$1{\beta}$, IL-6, IFN-${\gamma}$, LT-${\alpha}$, and TNF-${\alpha}$ were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-$1{\beta}$-511C/T, IL-6-174G/C, IFN-${\gamma}$+874T/A, LT-${\alpha}$+252A/G, and TNF-${\alpha}$-308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-${\alpha}$+252A/G and TNF-${\alpha}$-308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-${\gamma}$+874T/A were significantly higher than the variants in CCA cases. IFN-${\gamma}$+874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6-174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA.

• Journal of Life Science
• /
• v.20 no.3
• /
• pp.388-395
• /
• 2010

Cyclooxygenase (COX)-2 is generally known as an inducible enzyme, and it produces arachidonic acid to prostaglandin $E_2$ ($PGE_2$), which has been demonstrated to play a critical role in inflammation. In the present study, we investigated the effects of the extracts of fermented beans including soybean (FS), black agabean (FBA) and yellow agabean (FYA), on the expression of COXs and production of $PGE_2$ in U937 human promonocytic cells. Treatment of phorbol 12-myristate 13-acetate (PMA) significantly induced pro-inflammatory mediators such as COX-2 expression and $PGE_2$ production, whereas the levels of COX-1 remained unchanged. However, pre-treatment with FS, FBA and FYA significantly decreased PMA-induced COX-2 protein as well as mRNA, which is associated with inhibition of $PGE_2$ production. Moreover, FS, FBA and FYA markedly prevented the increase of nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$) p65 by PMA. Our data indicate that the extracts of fermented beans exhibits anti-inflammatory properties by suppressing the transcription of pro-inflammatory cytokine genes through the NF-${\kappa}B$ signaling pathway.

• Journal of Life Science
• /
• v.31 no.3
• /
• pp.287-297
• /
• 2021

Cornus officinalis Siebold & Zucc. is traditionally used as an edible and medicinal plant in many countries in East Asia. Previous studies have shown the pharmacological potential of extracts and components of C. officinalis, but comparative analysis of the composition of the leaf, stem, and fruit extracts has been insufficient to date. In the present study, the content of active antioxidant and anti-inflammatory ingredients was verified in different C. officinalis parts (under-ripe sansuyu, ripe sansuyu, seed, leaf, stem, and dried sansuyu). One active component, morroniside, was high in fruit (under-ripe and ripe sansuyu), while loganin was high in fruit (under-ripe sansuyu) and cornin was high in seeds. Total polyphenol contents were highest in fruit (ripe sansuyu) and flavonoids were highest in leaves. DPPH radical scavenging activity was highest in leaves, followed by seeds and then ripe sansuyu extract. The anti-inflammatory efficacy of leaf extracts of C. officinalis (LCO) was further investigated by measuring their effects on levels of nitric oxide (NO) and the pro-inflammatory cytokines interleukin (IL)-1β and IL-6 in RAW 264.7 macrophages. Non-cytotoxic concentrations of LCO effectively decreased the lipopolysaccharide (LPS)-induced expression of inducible NO synthase, resulting in decreased NO production. LCO also significantly suppressed LPS-induced production and expression of IL-1β and IL-6. Taken together, the present findings suggest that C. officinalis leaves have potential as natural materials for the development of antioxidant and anti-inflammatory agents.

• The Journal of the Convergence on Culture Technology
• /
• v.5 no.3
• /
• pp.317-326
• /
• 2019

The present study aimed to investigate the comparative evaluation of pharmacological efficacy between sulfasalazine alone and combination with herbal medicine on dextran sodium sulfate (DSS)-induced UC in mice. Balb/c mice received 5% DSS in drinking water for 7 days to induce colitis. Animals were divided into five groups (n = 9): group I-normal group, group II-DSS control group, group III-DSS + sulfasalazine (30 mg/kg), group IV-DSS + sulfasalazine (60 mg/kg), group V-DSS + sulfasalazine (30 mg/kg) + Radish Extract mixture (30 mg /kg) (SRE). DSS-treated mice developed symptoms similar to those of human UC, such as severe bloody diarrhea and weight loss. SRE supplementation, as well as sulfasalazine, suppressed colonic length and mucosal inflammatory infiltration. In addition, SRE treatment significantly reduced the expression of pro-inflammatory signaling molecules through suppression both MAPK) and nuclear factor-kappa B (NF-${\kappa}B$) signaling pathways, and prevented the apoptosis of colon. Moreover, SRE administration significantly led to the up-regulation of anti-oxidant enzyme including SOD and Catalase. This is the first report that Radish extract mixture combined with sulfasalazine protects against experimental UC via the inhibition of both inflammation and apoptosis, very similar to the standard-of-care sulfasalazin.