• The Korean Journal of Physiology
• /
• 제29권1호
• /
• pp.1-11
• /
• 1995

Alveolar macrophages play a pivotal role in the pathogenesis of silicosis since the macrophages may release a wide variety of toxic and inflammatory mediators as well as mitogenic growth factors. In the present study, the effects of in vitro exposure to silica on release of various mediator such as reactive oxygen species, platelet activating factor(PAF), and interleukin-1 (IL-1) by alveolar macrophages were examined. First, hydrogen peroxide release from alveolar macrophages was monitored by measuring the change in fluorescence of scopoletin in the absence or presence of graded concentration of silica. Significantly enhanced release of hydrogen peroxide was observed at 0.5 mg/ml and above. A maximal enhancement of 10 fold above control was observed at 5 mg/ml silica. Similarly, in vitro exposure to silica also significantly stimulated the generation of chemiluminescence from alveolar macrophages at 0.5 mg/ml and above with n maximal enhancement of 8 fold at 5 mg/ml silica. Second, PAF release from alveolar macrophages after 30 min incubation at $37^{\circ}C$ in absence or presence of zymosan and silica was determined by measuring $^{3}H-serotonin$ release ability of the conditioned macrophage supernates from platelets. 5 mg/ml zymosan as a positive control fur the PAF assay increased PAF release by 19 % of total serotonin release. Furthermore, silica also resulted in significant enhancement of the PAF release compared with that in unstimulated (control) cells, i.e., $17.7{\pm}5.8%$ and $24.0{\pm}4.9%$ of total serotonin release at 5 mg/ml and 10 mg/ml silica, respectively, which represents the release of nanomole levels of PAF. Lastly, IL-1 production by alveolar macrophages was analysed following their stimulation with lipopolysaccharide (LPS) and silica by their capacity to stimulate thymocyte proliferation. $10\;{\mu}g/ml$ LPS resulted in an 11 fold increase in IL-1 production. In comparison, $50\;{\mu}g/ml$ silica resulted in a 4 fold increase in IL-1 release. These data indicate that in vitro exposure of alveolar macrophages to silica activates the release of various bioactive mediators such as reactive oxygen species, PAF and IL-1 which thus contribute to amplification of inflammatory reactions and regulation of fibrotic responses by the lung after inhalation of silica.

• Journal of Microbiology and Biotechnology
• /
• 제17권2호
• /
• pp.348-358
• /
• 2007

Metallothionein, a cysteine-rich stress response protein that is naturally induced by a variety of immunologic stressors, has been shown to suppress autoimmune disorders through mechanisms not yet fully defined. In the present study, we examined the underlying mechanisms by which metallothionein might mediate such regulation of autoimmunity. $Na\ddot{i}ve\;CD4^+$ T cells from metallothionein-deficient mice differentiated to produce significantly less IL-10, $TGF-{\gamma}$, and repressor of GATA, but more $IFN-{\gamma}$ and T-bet, when compared with those from wild-type mice. The levels of IL-4 and GATA-3 production were not different between the two groups of mice. Conversely, treatment with exogenous metallothionein during the priming phase drove $na\ddot{i}ve$ wild-type $CD4^+\;T$ cells to differentiate into cells producing more IL-10 and $TGF-{\beta}$, but less $IFN-{\gamma}$ than untreated cells. Metallothionein-primed cells were hyporesponsive to restimulation, and suppressive to T cell proliferation in an IL-10-dependent manner. Lymphocytes from metallothionein-deficient mice displayed significantly elevated levels of AP-1 and JNK activities in response to stimulation compared with those from wild-type controls. Importantly, transgenic mice overexpressing metallothionein exhibited significantly reduced susceptibility to collagen-induced arthritis and enhanced IL-10 level in the serum, relative to their nontransgenic littermates. Taken together, these data suggest that metallothionein is able to promote the generation of IL-10-and $TGF-{\beta}$-producing type 1 regulatory T-like cells by downregulating JNK-dependent AP-1 activity. Thus, metallothionein may play an important role in the regulation of Th1-dependent autoimmune arthritis, and may represent both a potential target for therapeutic manipulation and a critical element in the diagnostic assessment of disease potential.

• Journal of Dairy Science and Biotechnology
• /
• 제29권2호
• /
• pp.17-23
• /
• 2011

The focus of this study was to clarify the relation between the nitric oxide (NO) production and cytokine expression including tumor necrosis factor-${\alpha}$ (TNF) and interleukin-6 (IL-6), and also investigated the effect of G-NANA (N-acylneuraminic acid isolates from glycomacropeptide) or S-NANA (Synthetic N-acylneuraminic acid) on LPS stimuli from RAW264.7 cell. The NANA is the predominant sialic acid found in mammalian cells and G-NANA is isolation of GMP (GMP is a valuable bioactive peptide with a varying degree of glycosylation including sialic acid). The lipopolysaccharide (LPS) of Gram-negative bacteria induces the expression of cytokines and potent inducers of inflammatory cytokines such as TNF-${\alpha}$ and IL-6. In this experiment, upon stimulation with increasing concentrations of chitosan, the LPS-stimulated TNF-${\alpha}$ and IL-6 secretion was significantly recovered with in the incubation media of RAW264.7 cells. Consistently, RT-PCR with mRNA and immunoblot analysis with anti-cytokine antiserum including TNF-${\alpha}$ and IL-6 showed that the amount of TNF-${\alpha}$ and IL-6 secretion in the incubation media recovered with the concentration of chitosan. The LPS-stimulated NO secretion was significantly recovered with in the 6 and 12 h incubation media of RAW264.7 cells, too. The recovery effect of G-NANA on IL-6 and NO secretion may be induced via the stimulus of TNF-${\alpha}$ in RAW264.7 cell. These results once again suggest that G-NANA may have the anti-inflammatory effect via the stimulus of TNF-${\alpha}$ in the LPS-stimulated inflammation in RAW264.7 cells.

• 한방안이비인후피부과학회지
• /
• 제17권2호
• /
• pp.12-30
• /
• 2004

This study was carried out to investigate the effects of SMG on the in vitro and in vivo inflammatory reactions. In experiment I, in vitro tests, ethanol extract of SMG showed potent radical scavenging activity tested by DPPH(I,1-diphenyl-2-picryl-hyrazyl) method and inhibited the lipopolysaccharide-induced gene expressions of interleukin-1${\beta}$, interleukin-6 and tumor necrosis factor-${\alpha}$ (above 50$\%$ at a concentration of 50㎍／㎖) by the macrophage RAW 246.7 cells. Among the herbal ingredients of SMG, ethanol extracts of Scutellaria baicalensis, Paeonia lactiflora, Glycyrrhiza glabra showed potent radical scavenging activity. And Glycyrrhiza glabra and Scutellaria baicalensis showed potent inhibitory activity of nitric oxide production. Especially, ethanol extract of Scutellaria baicalensis inhibited the gene expression of IL-1${\beta}$, IL-6 and TNF-${\alpha}$. In cyclooxygenase-2 assay, Scutellaria baicalensis and Glycyrrhiza glabra showed the potent inhibition of prostaglandin E2 generation. In experiment 2, in vivo tests, SMG showed inhibitory effects on vascular permeability (28.7$\%$) and leukocyte migration (11.5$\%$). These results mean that SMG has a anti-inflammatory effects by it's inhibitory effects of leukocyte migration and vascular permeability as well as it's inhibitory effects of lipopolysaccharide-induced gene expression of IL-1${\beta}$, IL-6 and TNF-${\alpha}$, and radical scavenging activity. Therefore, I expect that SMG may be used as a effective drug for treatment on inflammation.

• Parasites, Hosts and Diseases
• /
• 제60권4호
• /
• pp.229-239
• /
• 2022

The high percentage of Vermamoeba was found in tap water in Korea. This study investigated whether Vermamoeba induced allergic airway inflammation in mice. We selected 2 free-living amoebas (FLAs) isolated from tap water, which included Korean FLA 5 (KFA5; Vermamoeba vermiformis) and 21 (an homolog of Acanthamoeba lugdunensis KA/E2). We axenically cultured KFA5 and KFA21. We applied approximately 1×10⁶ to mice's nasal passages 6 times and investigated their pathogenicity. The airway resistance value was significantly increased after KFA5 and KFA21 treatments. The eosinophil recruitment and goblet cell hyperplasia were concomitantly observed in bronchial alveolar lavage (BAL) fluid and lung tissue in mice infected with KFA5 and KFA21. These infections also activated the Th2-related interleukin 25, thymic stromal lymphopoietin, and thymus and activation-regulated chemokines gene expression in mouse lung epithelial cells. The CD4⁺ interleukin 4⁺ cell population was increased in the lung, and the secretion of Th2-, Th17-, and Th1-associated cytokines were upregulated during KFA5 and KFA21 infection in the spleen, lung-draining lymph nodes, and BAL fluid. The pathogenicity (allergenicity) of KFA5 and KFA21 might not have drastically changed during the long-term in vitro culture. Our results suggested that Vermamoeba could elicit allergic airway inflammation and may be an airway allergen.

• Journal of Korean Neurosurgical Society
• /
• 제66권5호
• /
• pp.525-535
• /
• 2023

Objective : We performed an expanded multi-ethnic meta-analysis to identify associations between inflammation-related loci with intracranial aneurysm (IA) susceptibility. This meta-analysis possesses increased statistical power as it is based on the most data ever evaluated. Methods : We searched and reviewed relevant literature through electronic search engines up to August 2022. Overall estimates were calculated under the fixed- or random-effect models using pooled odds ratio (OR) and 95% confidence intervals (CIs). Subgroup analyses were performed according to ethnicity. Results : Our meta-analysis enrolled 15 studies and involved 3070 patients and 5528 controls including European, Asian, Hispanic, and mixed ethnic populations. Of 17 inflammation-related variants, the rs1800796 locus (interleukin [IL]-6) showed the most significant genome-wide association with IA in East-Asian populations, including 1276 IA patients and 1322 controls (OR, 0.65; 95% CI, 0.56-0.75; p=3.24#x00D7;10^-9) under a fixed-effect model. However, this association was not observed in the European population (OR, 1.09; 95% CI, 0.80-1.47; p=0.5929). Three other variants, rs16944 (IL-1β), rs2195940 (IL-12B), and rs1800629 (tumor necrosis factor-α) showed a statistically nominal association with IA in both the overall, as well as East-Asian populations (0.01<p<0.05). Conclusion : Our updated meta-analysis with increased statistical power highlights that rs1800796 which maps on the IL-6 gene is associated with IA, and in particular confers a protective effect against occurrence of IA in the East-Asian population.

• Journal of Microbiology and Biotechnology
• /
• 제28권1호
• /
• pp.65-76
• /
• 2018

Although there has been a steady increase in the prevalence of food allergies worldwide in recent decades, no effective therapeutic strategies have been developed. Modulation of the gut microbiota composition and/or function through probiotics has been highlighted as a promising target for protection against food allergies. In this study, we aimed to investigate the allergy-reducing effects of a probiotic mixture (P5: Lactococcus lactis KF140, Pediococcus pentosaceus KF159, Lactobacillus pentosus KF340, Lactobacillus paracasei 698, and Bacillus amyloliquefaciens 26N) in mice with ovalbumin (OVA)-induced food allergy. Administration of P5 significantly suppressed the oral OVA challenge-induced anaphylactic response and rectal temperature decline, and reduced diarrhea symptoms. Moreover, P5 also significantly inhibited the secretion of IgE, Th2 cytokines (interleukin (IL)-4, IL-5, IL-10, and IL-13), and Th17 cytokines (IL-17), which were increased in mice with OVA-induced food allergy, and induced generation of CD4+Foxp3+ regulatory T cells. These results revealed that P5 may have applications as a preventive agent against food allergy.

• Childhood Kidney Diseases
• /
• 제22권1호
• /
• pp.17-21
• /
• 2018

Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine that is an important trigger and initiator of many allergic diseases. TSLP promotes a T-helper type 2 (Th2) cytokine response that can be pathological. A relationship is formed both at the induction phase of the Th2 response through polarization of dendritic cells to drive Th2 cell differentiation and at the effector phase of the response, by promoting the expansion of activated T cells and their secretion of Th2 cytokines and TSLP. In transgenic mice with TSLP overexpression, it has been reported that TSLP leads to the development of mixed cryoglobulinemic membranoproliferative glomerulonephritis. In addition, TSLP can play an important role in the pathogenesis of IgA nephropathy and systemic lupus erythematosus-related nephritis. From our knowledge of the role of TSLP in the kidney, further studies including the discovery of new therapies need to be considered based on the relationship between TSLP and glomerulonephritis.

• Journal of Korean Biological Nursing Science
• /
• 제17권4호
• /
• pp.341-347
• /
• 2015

Purpose: Chrysanthemum indicum (CHI) has been used for edible and medical purposes for a long time in Korea. The purpose of this study was to evaluate the anti-inflammatory effects of CHI water extract in lipopolysaccharides (LPS)-induced RAW 264.7 macrophage cells. Methods: To investigate the anti-inflammatory effects on LPS-induced RAW 264.7 macrophage cells, CHI extract as a whole plant was used in this study. RAW 264.7 cells were treated with various concentrations of CHI extract (1, 10, and $100{\mu}g/mL$). After that Nitric Oxide (NO), inducible nitric oxide synthase (iNOS), interleukin (IL)-$1{\beta}$, cyclooxygenase (COX)-2 and prostaglandin $E_2$ ($PGE_2$) expression level were measured. Results: CHI extract significantly suppressed the LPS-induced NO production and decreased the level of iNOS, IL-$1{\beta}$, COX-2 messenger ribonucleic acid (mRNA) expression and also the down regulation of $PGE_2$ expression in a dose-dependent manner. Conclusion: The present study suggested that CHI extract can be substituted for anti-inflammatory drugs and provide a safe and effective non pharmacological therapeutic approach.

• 대한한의학방제학회지
• /
• 제17권1호
• /
• pp.99-111
• /
• 2009

Rheumatoid arthritis is characterized by focal loss of cartilage due to an up-regulation of inflammatory pathways, which produce pro-inflammatory mediators, such as interleukin-1(IL-1), tumour necrosis factor alpha($TNF-\alpha$), prostaglantin, and nitric oxide(NO). We investigated the anti-arthritic effects of water extracts from Pellodendri cortex and Atractylodis rhizoma in vitro and in vivo. Each extract suppressed the production of inflammatory mediators(NO, $IL-1\beta$, $TNF-\alpha$, and prostaglandin $E_2$) and the expression of inducible NO synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated macrophages in a dose-dependent manner. These suppressive effects were synergistically increased by their combination. The same results were also observed in the rat osteoblast sarcoma cell line ROS17/2.8 stimulated with $IL-1\beta$, $IFN-\gamma,$ and $TNF-\alpha$. Moreover, the combination of these water extracts significantly suppressed collagen-induced mouse arthritis. These results suggest that the combination of water-extractable components of Pellodendri cortex and Atractylodis rhizoma may be useful for therapeutic drugs against rheumatoid arthritis, probably by suppressing the production of inflammatory mediators.