• Natural Product Sciences
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• v.16 no.3
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• pp.185-191
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• 2010

Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In the present study, the effect of water extract of Gleditsiae Spina (WGS) (Leguminosae), on compound 48/80-induced systemic allergic reaction, anti-DNP IgE antibody-induced local allergic reaction, and histamine release from human mast cell line (HMC-1) cells were studied. In addition, the effect of WGS on phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-induced gene expression and secretion of pro-inflammatory cytokines were investigated using HMC-1 cells. WGS was anally administered to mice for high and fast absorption. WGS inhibited compound 48/80-induced systemic allergic reaction. WGS dose-dependently decreased the IgE-mediated passive cutaneous anaphylaxis. WGS reduced histamine release from HMC-1 cells. In addition, WGS decreased the gene expression and secretion of pro-inflammatory cytokines in PMA plus A23187-stimulated HMC-1 cells. These findings provide evidence that WGS could be a candidate as an antiallergic agent.

• Journal of Microbiology
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• v.42 no.2
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• pp.117-125
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• 2004

Propionibacterium acnes (P. acnes) plays an important role in the disease pathogenesis of acne vulgaris, a disorder of pilosebaceous follicles, seen primarily in the adolescent age group. In the present study, the presence of antibodies against P. acnes (MTCC1951) were detected in acne patient (n=50) and disease free controls (n=25) using dot-ELISA and Western blot assay. The ability of P. acnes to induce pro-inflammatory cytokines by human peripheral blood mononuclear cells (PBMCs), obtained from acne patients and healthy subjects, were also analysed. The patients (n=26) who were culture positive for skin swab culture, were found to have a more advanced disease and higher antibody titres (1:4000 to >1:16000) compared to the P. acnes negative patients (n=24) and normal controls (n=25). An analysis of patients' sera by western blot assay recognized a number of antigenic components of P. acnes, rang-ing from 29 to 205 kDa. The major reactive component was an approximately 96 kDa polypeptide, which was recognised in 92％ (24 of 26) of the patients sera. Further, the P. acnes culture supernatant, crude cell lysate and heat killed P. acnes whole cells, obtained from 72-h incubation culture, were observed to be able to induce significant amounts of IL-8 and tumor necrosis factor alpha (TNF-${\alpha}$) by the PBMCs in both the healthy subjects and patients, as analysed by cytokine-ELISA. The levels of cytokines were significantly higher in the patients than the healthy subjects. A major 96 kDa polypep-tide reactant was eluted from the gel and was found to cause dose dependent stimulation of the pro-ductions of IL-8 and TNF-${\alpha}$. Thus, the above results suggest that both humoral and pro-inflammatory responses play major roles in the pathogenesis of acne.

• Restorative Dentistry and Endodontics
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• v.31 no.3
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• pp.203-214
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• 2006

Dental pulp is a loose, mesenchymal tissue almost entirely enclosed in the dentin. It consists of cells, ground substance, and neural and vascular supplies. Damage to the dental pulp by mechanical, chemical, thermal, and microbial irritants can provoke various types of inflammatory response. Pulpal inflammation leads to the tissue degradation, which is mediated in part by Matrix metalloproteinase leads to accelerate extracellular matrix degradation with pathological pathway We have now investigated the induction of MMPs and inflammatory cytokines by Lipopolysaccharide (LPS) control of inflammatory mediators by peroxisome proliferator-activated receptors (PPARs). Human dental pulp cells exposed to various concentrations of LPS ($1-10{\mu}g/ml$) revealed elevated levels of MMP-2 and MMP-9 at 24 hrs of culture. LPS also stimulated the production of ICAM-1, VCAM-1, $IL-1{\beta},\;and\;TNF-{\alpha}$. Adenovirus $PPAR{\gamma}\;(Ad/PPAR{\gamma})\;and\;PPAR{\gamma}$ agonist rosiglitazone reduced the synthesis of MMPs, adhesion molecules and pro-inflammatory cytokines. The inhibitory effect of $Ad/PPAR{\gamma}$ was higher than that of $PPAR{\gamma}$ agonist. These result offer new insights in regard to the anti-inflammatory potential of $PPAR{\gamma}$ in human dental pulp cell.

• Journal of the Korea Convergence Society
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• v.13 no.1
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• pp.101-107
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• 2022

Tertomotide is a peptide vaccine developed for anti-cancer therapy. Since it has been found to ameliorate inflammatory symptoms in animal studies and clinical test, we investigated anti-inflammation activity of the tertomotide and the mechanism of action in monocyte in order to assess if tertomotide may serve as an anti-inflammatory agent by checking inflammatory cytokines and related signaling pathway following tertomotide treatment. We found that tertomotide reduced the level of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-8 in LPS- or PMA-stimulated monocyte cell line and suppressed NF-κB signaling including the activation of ERK1/2 and P38 MAPK following TNF-α treatment. These results may correlate to the beneficial findings in animal studies, implicating that tertomotide may act as a potential anti-inflammatory agent. This study is an exemplary case for convergence that a computationally designed peptide for immunological purpose exerting unexpected biological activity may elicit novel anti-inflammatory drug.

• YAKHAK HOEJI
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• v.55 no.6
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• pp.456-461
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• 2011

The aim of the present study is to investigate the anti-inflammatory effect of a Rice Bran Ethanol Extract (RBE). Inflammation, such as a bacterial infection in vivo metabolites, such as external stimuli or internal stimuli to the defense mechanisms of the biological tissue a variety of intracellular regulatory factors deulin inflammatory TNF-${\alpha}$, IL-$1{\beta}$, IL-6, IL-8, such as proinflammatory cytokines, prostagrandin, lysosomal enzyme, free radicals are involved in a variety of mediators. The present study was designed to determine the effect of the RBE on pro-inflammatory factors such as NO, iNOS expression and TNF-${\alpha}$, IL-$1{\beta}$, IL-6 in lipopolysaccharide (LPS) - stimulated RAW264.7 macrophages cells. The cell toxicity was determined by MTS assay. To evaluate of anti-inflammatory effect of RBE, amount of NO was measured using the NO detection kit and the iNOS expression was measured by reverse transcriptase polymerase chain reaction (RT-PCR). And proinflammatory cytokines were measured by ELISA kit. As a result, the RBE reduced NO, iNOS expression and TNF-${\alpha}$, IL-$1{\beta}$, IL-6 production without cytotoxicity. Our results suggest that the RBE may have an anti-inflammatory property through suppressing inflammatory mediator productions and appears to be useful as an anti-inflammatory material.

• Korean Journal of Biological Psychiatry
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• v.13 no.1
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• pp.32-37
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• 2006

Background : Several studies have suggested that alterations of cytokine level could be related to the pathophysiology of bipolar disorder. In this study, we measured plasma level of Interleukin-12(IL-12), a pro-inflammatory cytokine and transforming growth factor-${\beta}$1(TGF-${\beta}$1), an anti-inflammatory cytokine before and after treatment in acute manic patients. Methods : The plasma concentrations of IL-12 and TGF-${\beta}$1 were measured using quantitative ELISA in 18 bipolar disorder patients and 25 normal controls at admission and 6 weeks later. The psychopathology was measured by Brief Psychiatric Rating Scale(BPRS) and Young Mania Rating Scale(YMRS). Results : IL-12 levels were significantly higher in bipolar manic patients than in controls before treatment. Following the 6-week treatment, the IL-12 level was decreased than before treatment, but sustained still higher level than normal control. TGF-${\beta}$1 level was not significant different between manic patients and normal controls before treatment, but was increased after treatment comparing with before treatment in bipolar patients. The ratio of IL-12 and TGF-${\beta}$1 was significantly decreased after treatment. Conclusion : Cytokine abnormalities in bipolar disorder might be involved in the pathophysiology of the illness. It is possible that TGF-${\beta}$1 plays an important role in the regulation of immunological imbalance in bipolar disorder.

• BMB Reports
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• v.52 no.5
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• pp.336-341
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• 2019

The cGAS-STING pathway plays an important role in pathogen-induced activation of the innate immune response. The 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) found predominantly in the synovial fluid of osteoarthritis (OA) patients increases the expression of catabolic factors via the toll-like receptor-2 (TLR-2) signaling pathway. In this study, we investigated whether 29-kDa FN-f induces inflammatory responses via the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) pathway in human primary chondrocytes. The levels of cGAS and STING were elevated in OA cartilage compared with normal cartilage. Long-term treatment of chondrocytes with 29-kDa FN-f activated the cGAS/STING pathway together with the increased level of gamma-H2AX, a marker of DNA breaks. In addition, the expression of pro-inflammatory cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF-2), granulocyte colony-stimulating factor (G-CSF/CSF-3), and type I interferon ($IFN-{\alpha}$), was increased more than 100-fold in 29-kDa FN-f-treated chondrocytes. However, knockdown of cGAS and STING suppressed 29-kDa FN-f-induced expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ together with the decreased activation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and inhibitor protein ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$). Furthermore, NOD2 or TLR-2 knockdown suppressed the expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ as well as decreased the activation of the cGAS/STING pathway in 29-kDa FN-f-treated chondrocytes. These data demonstrate that the cGAS/STING/TBK1/IRF3 pathway plays a critical role in 29-kDa FN-f-induced expression of pro-inflammatory cytokines.

• Journal of Microbiology and Biotechnology
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• v.32 no.2
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• pp.141-148
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• 2022

Many bone diseases such as osteolysis, osteomyelitis, and septic arthritis are caused by gram-negative bacterial infection, and lipopolysaccharide (LPS), a bacterial product, plays an essential role in this process. Drugs that inhibit LPS-induced osteoclastogenesis are urgently needed to prevent bone destruction in infective bone diseases. Marein, a major bioactive compound of Coreopsis tinctoria, possesses anti-oxidative, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic effects. In this study, we measured the effect of marein on RAW264.7 cells by CCK-8 assay and used TRAP staining to determine osteoclastogenesis. The levels of osteoclast-related genes and NF-κB-related proteins were then analyzed by western blot, and the levels of pro-inflammatory cytokines were quantified by ELISA. Our results showed that marein inhibited LPS-induced osteoclast formation by osteoclast precursor RAW264.7 cells. The effect of marein was related to its inhibitory function on expressions of pro-inflammatory cytokines and osteoclast-related genes containing RANK, TRAF6, MMP-9, CK, and CAII. Additionally, marein leads to markedly inhibited NF-κB signaling pathway activation in LPS-induced RAW264.7 cells. Concurrently, when the NF-κB signaling pathway was inhibited, osteoclast formation and pro-inflammatory cytokine expression were decreased. Collectively, marein could inhibit LPS-induced osteoclast formation in RAW264.7 cells via regulating the NF-κB signaling pathway. Our data demonstrate that marein might be a potential drug for bacteria-induced bone destruction disease. Our findings provide new insights into LPS-induced bone disease.

• Biomedical Science Letters
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• v.29 no.4
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• pp.211-219
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• 2023

Caffeic acid phenethyl ester (CAPE) is an active component of propolis obtained from honeybee hives. CAPE possesses anti-mitogenic, anti-carcinogenic, anti-inflammatory, and immunomodulatory activities in diverse systems, which know as displays antioxidant activity and inhibits lipoxygenase activities, protein tyrosine kinase, and nuclear factor kappa B (NF-κB) activation. This study aimed to investigate the effect of CAPE on lipopolysaccharide (LPS)-induced human neutrophil phagocytosis. Human neutrophils were cultured with various concentrations of CAPE (1, 10, and 100 µM) with or without LPS. The pro-inflammatory proteins (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6 and IL-8) levels were measured after 4 h incubation. To investigate the intracellular signaling pathway, we measured the levels of mitogen-activated protein kinases (MAPK), including phosphorylation of p38, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Next, to evaluate the potential phagocytosis, neutrophils were labeled with iron particles of superparamagnetic iron oxide nanoparticles (SPIONs, 40 nm) for 1 h in culture medium containing 5 mg/mL of iron. The labeling efficiency was determined by Prussian blue staining for intracellular iron and 3T-wighted magnetic resonance imaging. CAPE decreased the activation of intracellular signaling pathways, including ERK1/2 and c-Jun, and expression of pro-inflammatory cytokines, including TNF-α and IL-6, but had no effect on the signaling pathways of p38 and cytokine IL-8. Furthermore, images obtained after mannan-coated SPION treatment suggested that CAPE induced significantly higher signal intensities than the control or LPS group. Together, these results suggest that CAPE regulates LPS-mediated activation of human neutrophils to reduce phagocytosis.

• BMB Reports
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• v.45 no.6
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• pp.371-376
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• 2012

To investigate the therapeutic effect of a Korean herbal medicine Pulsatilla koreana as an anti-septic agent, anti-inflammatory effects of the herbal medicine were determined in lipopolysaccharide (LPS)-exposed rats. Treatment with a methanol extract from Pulsatilla koreana significantly inhibited LPS-induced inflammatory responses. Results from ELISA analysis showed that Pulsatilla koreana decreased the plasma and hepatic levels of pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$ while increased the level of anti-inflammatory cytokine IL-10 in LPS-exposed rats. Pulsatilla koreana also decreased the plasma levels of other inflammatory mediators such as $NO_3{^-}/NO_2{^-}$, ICAM-1, $PGE_2$, and CINC-1 in LPS-exposed rats. Although no significant effects were observed in the phagocytic activities, the distribution of lymphocyte population was significantly shifted by the treatment with Pulsatilla koreana. All together, Pulsatilla koreana exerts anti-inflammatory activities in the immune-challenged animals implicating that this Korean herbal medicine is therapeutically useful for the treatment of inflammatory diseases like sepsis.