• BMB Reports
• /
• 제36권1호
• /
• pp.128-137
• /
• 2003

Matrix metalloproteinases (MMPs), zinc dependent proteolytic enzymes, cleave extracellular matrix (ECM: collagen, laminin, firbronectin, etc) as well as non-matrix substrates (growth factors, cell surface receptors, etc). The deregulation of MMPs is involved in many diseases, such as tumor metastasis, rheumatoid arthritis, and periodontal disease. Metastasis is the major cause of death among cancer patients. In this review, we will focus on the roles of MMPs in tumor metastasis. The process of metastasis involves a cascade of linked, sequential steps that involve multiple host-tumor interactions. Specifically, MMPs are involved in many steps of tumor metastasis. These include tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Therefore, without MMPs, the tumor cell cannot perform successful metastasis. The activities of MMPs are tightly regulated at the gene transcription levels, zymogen activation by proteolysis, and inhibition of active forms by endogenous inhibitors, tissue inhibitor of metalloproteinase (TIMP), and RECK. The detailed regulations of MMPs are described in this review.

• 생약학회지
• /
• 제50권4호
• /
• pp.277-284
• /
• 2019

Rumex crispus is known to have anticancer, antioxidant, antibacterial, and bone loss inhibitory activities. Mast cells are critical immune cells that induce a type 1 IgE-mediated allergic reaction. However, there are no reports of inhibitory effects of Rumex crispus on mast cells and allergic reactions. In this study, we performed some experiments to investigate whether Rumex crispus ethanol extract(RCE) has any inhibitory effect on antigen-induced type I allergic response in vitro and in vivo. RCE inhibited degranulation of IgE-mediated mast cells(IC₅₀, ~57 ㎍/ml) and cytokine production such as TNF-α and IL-4 in a dose-dependent manner. In vivo, RCE significantly inhibited passive cutaneous anaphylaxis(PCA)(ED₅₀, ~198 mg/kg) in mice. Furthermore, RCE inhibited degranulation of MCs in ear tissue of mice with PCA. Mechanism studies showed that RCE inhibited the activation of Syk and Syk-dependent pathway such as LAT, PLC-γ, Akt, and MAP Kinase. Our results demonstrate for the first time that RCE inhibits type I hypersensitive response by suppressing the activity of Syk in mast cells, thereby reducing degranulation and cytokine production. Taken together, RCE could be used as a novel therapeutic material to suppress allergic diseases.

• 생약학회지
• /
• 제38권2호통권149호
• /
• pp.117-122
• /
• 2007

The specific activation of the immune system to control cancer growth in vivo has been a long-standing goal in cancer immunology. Whole tumor Iysates have been used either alone or combined with adjuvants to induce specific immune response in vivo. Here, we examined whether freezing/thawing (F/T) colon26-M3.1 tumor cell admixed with EN-3, glycoprotein purified from Acanthopanx Senticosus, could stimulate in vivo immunity by using a murine experimental tumor metastasis model produced by colon26-M3.1 carcinoma cells. Vaccination of mice with F/T treated colon26-M3.1 carcinoma cells in combination with EN-3 as an adjuvant resulted in a significant inhibition in tumor metastasis of mice against live colon26-M3.1 carcinoma challenge. In addition, the splenocytes from vaccinated mice exhibited a higher proliferating activity and secreted interferon-${\gamma}$. These results suggest that EN-3 can be applied to immunoadjuvant to enhance the antitumor immunity in vivo.

• Journal of Microbiology and Biotechnology
• /
• 제19권5호
• /
• pp.455-461
• /
• 2009

There is a significant amount of experimental evidence suggesting that polysaccharides from mushrooms enhance the host immune system by activating various mechanisms in immune cells, including macrophages. In this study, polysaccharides from Lentinus edodes were found to stimulate the functional activation of macrophages to secrete inflammatory mediators and cytokines and increase the phagocytotic uptake. The chemical properties of the stimulatory polysaccharides, CPFN-G-I, CPBN-G, and CPBA-G, were determined based on their monosaccharide composition, which mainly consisted of glucose and mannose. According to FT-IR and GC/MS, the structure of CPFN-G-I, purified from the fruiting body of L. edodes, was found to consist of a $\beta$-1,6-branched-$\beta$-1,4-glucan, whereas CPBN-G and CPBA-G, purified from the liquid culture broth, were found to be composed of a heteromannan. The configuration of the p-linkage and triple helical conformation of each polysaccharide were confirmed using a Fungi-Fluor kit and Congo red, respectively.

• Asian-Australasian Journal of Animal Sciences
• /
• 제27권9호
• /
• pp.1360-1367
• /
• 2014

Triplicate groups of fed and starved olive flounder, Paralichthys olivaceus (body weight: $119.8{\pm}17.46$ g), were examined over 42 days for physiological changes using hematological, biochemical, and non-specific immune parameters. No significant differences in concentrations of blood hemoglobin and hematocrit and plasma levels of total cholesterol, aspartate aminotransferase, alanine aminotransferase, glucose, and cortisol were detected between fed and starved groups at any sampling time throughout the experiment. In contrast, plasma total protein concentrations were significantly lower in starved fish than in fed fish from day 7 onwards. Moreover, plasma lysozyme concentrations were significantly higher in starved flounder from day 21 onwards. This result confirms that the response of olive flounder to short-term (less than about 1.5 months) starvation consists of a readjustment of metabolism rather than the activation of an alarm-stress response. The present results indicate that starvation does not significantly compromise the health status of fish despite food limitation.

• Journal of Microbiology and Biotechnology
• /
• 제29권11호
• /
• pp.1852-1859
• /
• 2019

Chikungunya virus (CHIKV) is a single-stranded positive-sense RNA virus, belonging to the genus Alphavirus of the Togaviridae family. It causes multiple symptoms, including headache, fever, severe joint and muscle pain, and arthralgia. Since CHIKV was first isolated in Tanzania in 1952, there have been multiple outbreaks of chikungunya fever. However, its pathogenesis and mechanisms of viral immune evasion have been poorly understood. In addition, the exact roles of individual CHIKV genes on the host innate immune response remain largely unknown. To investigate if CHIKV-encoded genes modulate the type I interferon (IFN) response, each and every CHIKV gene was screened for its effects on the induction of the IFN-β promoter. Here we report that CHIKV nsP2, E2 and E1 strongly suppressed activation of the IFN-β promoter induced by the MDA5/RIG-I receptor signaling pathway, suggesting that nsP2, E2, and E1 are the major antagonists against induction of IFN-β. Delineation of underlying mechanisms of CHIKV-mediated inhibition of the IFN-β pathway may help develop virus-specific therapeutics and vaccines.

• IMMUNE NETWORK
• /
• 제12권3호
• /
• pp.104-112
• /
• 2012

Silica is one of the most abundant compounds found in nature. Immoderate exposure to crystalline silica has been linked to pulmonary disease and crystalline silica has been classified as a Group I carcinogen. Ultrafine (diameter <100 nm) silica particles may have different toxicological properties compared to larger particles. We evaluated the effect of ultrafine silica nanoparticles on mouse bone marrow-derived dendritic cells (BMDC) and murine dendritic cell line, DC2.4. The exposure of dendritic cells (DCs) to ultrafine silica nanoparticles showed a decrease in cell viability and an induction of cell death in size- and concentration-dependent manners. In addition, in order to examine the phenotypic changes of DCs following co-culture with silica nanoparticles, we added each sized-silica nanoparticle along with GM-CSF and IL-4 during and after DC differentiation. Expression of CD11c, a typical DC marker, and multiple surface molecules such as CD54, CD80, CD86, MHC class II, was changed by silica nanoparticles in a size-dependent manner. We also found that silica nanoparticles affect inflammatory response in DCs in vitro and in vivo. Finally, we found that p38 and NF-${\kappa}B$ activation may be critical for the inflammatory response by silica nanoparticles. Our data demonstrate that ultrafine silica nanoparticles have cytotoxic effects on dendritic cells and immune modulation effects in vitro and in vivo.

• Journal of the Korean Society for Industrial and Applied Mathematics
• /
• 제19권2호
• /
• pp.137-170
• /
• 2015

In this paper, we propose and analyze three viral infection models with humoral immunity including an eclipse stage of infected cells. The incidence rate of infection is represented by bilinear incidence and saturated incidence in the first and second models, respectively, while it is given by a more general function in the third one. The neutralization rate of viruses is giv0en by bilinear form in the first two models, while it is given by a general function in the third one. For each model, we have derived two threshold parameters, the basic infection reproduction number which determines whether or not a chronic-infection can be established without humoral immunity and the humoral immune response activation number which determines whether or not a chronic-infection can be established with humoral immunity. By constructing suitable Lyapunov functions we have proven the global asymptotic stability of all equilibria of the models. For the third model, we have established a set of conditions on the threshold parameters and on the general functions which are sufficient for the global stability of the equilibria of the model. We have performed some numerical simulations for the third model with specific forms of the incidence and neutralization rates and have shown that the numerical results are consistent with the theoretical results.

• 한국식품영양학회지
• /
• 제23권2호
• /
• pp.135-140
• /
• 2010

Acorns have been used as a traditional remed as well as food source. However, few studies on their immunomodulating effects have been reported. In this study, the combined immunomodulative effect of a water extract of acorns was tested on seven to eight weeks old mice(balb/c). The mice were fed ad libitum on a chow diet, and a water extract of the plant mixture was orally administered every other day for four weeks at two different concentrations(50 and 500 mg/kg B.W.). The production of cytokine(IL-$1{\beta}$, IL-6, IL-2, IL-10, IFN-$\gamma$), secreted by macrophages stimulated with LPS or not, detected by ELISA assay using cytokine kit. After 48 h of incubation with mitogen(ConA or LPS) ex vivo study showed that cytokine (IL-$1{\beta}$, IL-6, IL-2, IL-10, IFN-$\gamma$) was detected in both of the 50 and 500 mg/kg B.W. supplementation groups with LPS stimulation. The results of this study may suggest that supplementation with acorn water extract increase immune function by regulating cytokine production capacity by activated macrophages.

• 대한본초학회지
• /
• 제25권1호
• /
• pp.33-38
• /
• 2010

Objectives : This study was designed to investigate therapeutic effects fo NR on allergic asthma in terms of measurement of cytokine profiles, distribution of BAL and expression levels of asthma induced by OVA. Methods : C57BL/6 mouse was divided into normal, NRI, control, and NRII, and Notopterygii Rhizoma Extract was orally administered to the C57BL/6 mice in the normal group and the normal mouse in NRI group while it was orally administered to the control group after inducing asthma by OVA and NRII. The study measured them by means of ELISA after dividing BALF of each group, and analyzed RT-PCR by using lung tissues. Results : In our results, lung weight and the number of total cells in the lung and of Leukocyte and Eosinophils in BALF were significantly decreased. In addition, IL-4, IL-5, IL-13, and IgE in BALF were significantly decreased compared to the control group. Conclusions : These results demonstrate that NR Extract be a desirable altemative therapy for allergic asthma by inhibiting the expressin of immune cells, the activation of inflammatory mediator.