• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8539-8548
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• 2014

Mitogen-activated protein kinase (MAPK) is an important signaling pathway in living beings in response to extracellular stimuli. There are 5 main subgroups manipulating by a set of sequential actions: ERK(ERK1/ERK2), c-Jun N(JNK/SAPK), p38 MAPK($p38{\alpha}$, $p38{\beta}$, $p38{\gamma}$ and $p38{\delta}$), and ERK3/ERK4/ERK5. When stimulated, factors of upstream or downstream change, and by interacting with each other, these groups have long been recognized to be related to multiple biologic processes such as cell proliferation, differentiation, death, migration, invasion and inflammation. However, once abnormally activated, cancer may occur. Several components of the MAPK network have already been proposed as targets in cancer therapy, such as p38, JNK, ERK, MEK, RAF, RAS, and DUSP1. Among them, alteration of the RAS-RAF-MEK-ERK-MAPK(RAS-MAPK) pathway has frequently been reported in human cancer as a result of abnormal activation of receptor tyrosine kinases or gain-of-function mutations in genes. The reported roles of MAPK signaling in apoptotic cell death are controversial, so that further in-depth investigations are needed to address these controversies. Based on an extensive analysis of published data, the goal of this review is to provide an overview on recent studies about the mechanism of MAP kinases, and how it generates certain tumors, as well as related treatments.

• Korean Journal of Veterinary Research
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• v.34 no.2
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• pp.301-306
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• 1994

This study was planned to estimate the activity of bovine circulating blood lymphocytes using phytohemagglutinin-M(PHA) known as T cell mitogen. Bovine circulating blood mononuclear cells(MNCs) was separated, and cultured with or without macrophage($PHA^+/M{\phi}^+$ or $PHA^+/M{\phi}^-$) in conditioned medium which stimulated with various concentration of PHA(0, 5, 10, 15 and $20{\mu}g/ml$ in medium), and then investigated the blastogenic response and rosette formation of lymphocytes. Blastogenic rate(BR) was especially increased in PHA concentration(10 and $15{\mu}g/ml$) of $PHA^+/M{\phi}^+$ group and their BR were $41.5{\pm}6.8%$ and $44.4{\pm}8.9%$, respectively and BR in PHA concentration(15 and $20{\mu}g/ml$) of $PHA^+/M{\phi}^-$ group was $32.8{\pm}6.2%$ and $31.4{\pm}4.6%$, respectively. BR of lymphocytes was more increased in $PHA^+/M{\phi}^+$ than $PHA^+/M{\phi}^-$ group when these cells were stimulated by PHA. Rosette forming rate(RFR) of lymphocytes to SRBC highly increased when SRBC was treated with AET and/or dextran, respectively. On the orther hand, RFR significantly increased more in $PHA^+/M{\phi}^+$ and $PHA^+/M{\phi}^-$ group than in control group, but when compared with two groups, statistical significancy was recognized only in PHA concentration($15{\mu}g/ml$, p<0.026) of $PHA^+/M{\phi}^+$ group.

• Journal of Microbiology and Biotechnology
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• v.11 no.1
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• pp.143-152
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• 2001

Korean-style fermented soybean paste (KFSP), Doenjang, is a traditional food that is consumed as a protein source in Korea. Recently, efforts to identify biolgocial response modifiers (BRMs) have been focused on food products. Accordingly, this study which isolated abiologically active substance form KFSP, named KFSP-BRM, ws defined to be aheat-stable carbohydrate with a molecular weight of 2,000 kDa. The biological activity of KFSP-BRM was not inactivated by treatment with an anti-LPS antibody. The oral as well as intraperitoneal treatment of mice with KFSP-BRM significantly enhanced the number of B cells expressing surface significantly enhanced the number of B cells expressing surface immunoglobulins (IgM and IgG). Subsequently, an increased level of immunoglobulins in the sera was also observed. In vitro. KFSP-BRM was found to upregulate the production of interleukin-1 (IL-1) and IL-6 by mactro phages and B cells but not the production of IL-2 by T cells. In conclusion, these data demonstrate the presence of a BRM in KFSP, which may provide an additional benefit to those consuming it is a food. KFSP-BRM is a novel B cellmitogen distinct from fresh soybean lectin or B cell mitogens, such as LPS and Streptococcus protein A. The major biological effects of KFSP-BRM would appear to be anincreased production of IL-1 and IL-6 by macrophages and B cells, thereby enhancing the function of mature B cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.28 no.4
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• pp.924-933
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• 1999

This study investigated the effects of vitamin E supplementation on immune responses and antioxidant status in healthy Korean old and young women. Blood samples were obtained from 15 healthy old women (over 60 years old) and from 15 healthy young women(20 years old) before and 4 weeks after vitamin E( tocopherol acetate) supplementation(400IU/day). Daily nutrient intakes were calculated, and plasma vitamin E concentration, numbers and percentages of white blood cell and their subpopulation, percentages of lymphocytes and subpopulation, NK cell percentages, plasma immunoglobulin A, G, M and C3 concentration, proliferation of PMN with mitogen were measured. Also plasma TBARS concentration and radical scavenger activity of erythrocytes were investigated. Plasma vitamin E concentrations were significantly increased after supplementation in both groups. In elderly women, vitamin E supplementation restored the per centages of neutrophils, lymphocytes, and eosinophils which had been out of normal ranges before supple mentation. And after vitamin E supplementation, helper T cell percentages significantly increased in elderly. Plasma immunoglobulin and complement C3 concentrations were not affected by vitamin E supplementation in both groups. PMN proliferations with mitogen were significantly lower in old women than in young women, and there was no effect of vitamin E supplementation. Vitamin E supplementation significantly decreased plasma TBARS concentrations in old and young women. RSA of erythrocytes was increased in both groups, but the statistical significant was only found in young women group. Therefore, these results suggest that the moderate vitamin E supplementation in old women improves immune responses, especially nonspecific immunity and cell mediated immunity, via protection of oxidant stress.

• The Korea Journal of Herbology
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• v.30 no.6
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• pp.33-38
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• 2015

Objectives : Portulaca oleracea (PO) have been used as a traditional medicine to treat inflammatory diseases in Korea. However, the anti-inflammatory effect of PO ethanol extract on lipopolysaccharide (LPS)-induced inflammation is not well-known. Therefore, this study was performed to identify the anti-inflammatory effect of PO on LPS induced inflammatory.Methods : Identification of PO was conducted by comparison with purified standards by HPLC. To measure out the cytotoxicity of PO, author performed the MTT assay. To evaluate the anti-inflammatory effects of PO, author examined the inflammatory mediators such as nitric oxide (NO) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin, (IL)-1β and IL-6) on RAW 264.7 cells. Author also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-κB) activation by western blot.Results : Three major components (peaks 1, 2, 3) were detected in both varieties and peak 1 was characterized as caffeic acid, peak 2 as p-coumaric acid, and peak 3 as ferulic acid by comparison of chromatographic properties with authentic standards. Extract from PO itself did not have any cytotoxic effect in RAW 264.7 cells. PO inhibited LPS-induced productions of inflammatory mediators such as NO and pro-inflammatory cytokines in RAW 264.7cells. In addition, PO inhibited the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), c-Jun NH₂-terminal kinase (JNK) and NF-κB activation in RAW 264.7 cells.Conclusions : Above experiment data can be an important indicator for the identification of PO and this study suggest that treatment of PO could reduce the LPS-induced inflammation. Thereby, PO could be used as a protective agent against inflammation.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.447-453
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• 2012

TLR6 forms a heterodimer with TLR2 and TLR4. While proinflammatory roles of TLR2 and TLR4 are well documented, the role of TLR6 in inflammation is poorly understood. In order to understand mechanisms of action of TLR6 in inflammatory responses, we investigated the effects of FSL-1, the TLR6 ligand, on expression of chemokine CCL2 and cytokine IL-$1{\beta}$ and determined cellular factors involved in FSL-1-mediated expression of CCL2 and IL-$1{\beta}$ in mononuclear cells. Exposure of human monocytic leukemia THP-1 cells to FSL-1 resulted not only in enhanced secretion of CCL2 and IL-$1{\beta}$, but also profound induction of their gene transcripts. Expression of CCL2 was abrogated by treatment with OxPAPC, a TLR-2/4 inhibitor, while treatment with OxPAPC resulted in partially inhibited expression of IL-$1{\beta}$. Treatment with FSL-1 resulted in enhanced phosphorylation of Akt and mitogen-activated protein kinases and activation of protein kinase C. Treatment with pharmacological inhibitors, including SB202190, SP6001250, U0126, Akt inhibitor IV, LY294002, GF109203X, and RO318220 resulted in significantly attenuated FSL-1-mediated upregulation of CCL2 and IL-$1{\beta}$. Our results indicate that activation of TLR6 will trigger inflammatory responses by upregulating expression of CCL2 and IL-$1{\beta}$ via TLR-2/4, protein kinase C, PI3K-Akt, and mitogen-activated protein kinases.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.107-113
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• 2009

Olibanum (Boswellia serrata) has been shown to have anti-inflammatory, anti-arthritic and anticancer effects. This study determined the role of a water extract of olibanum in platelet-derived growth factor (PDGF)-stimulated proliferation and migration of rat aortic smooth muscle cells (RASMCs). PDGF-BB induced the migration and proliferation of RASMCs that were inhibited by olibanum extract in a dose-dependent manner. The PDGF-BB-increased phosphorylation of p38 mitogen-activated protein kinase (MAPK); the heat shock protein (Hsp) 27 was significantly inhibited by the olibanum extract. The effects of PDGF-BB-induced extracellular signal-regulated kinase1/2 was not altered by the olibanum extract. Treatment with olibanum extract inhibited PDGF-BB-stimulated sprout out growth of aortic rings. These results suggest that the water extract of olibanum inhibits PDGF-BB-stimulated migration and proliferation in RASMCs as well as sprout out growth, which may be mediated by the inhibition of the p38 MAPK and Hsp27 pathways.

• Physical Therapy Rehabilitation Science
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• v.3 no.1
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• pp.33-37
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• 2014

Objective: Low intensity pulsed ultrasound (LIPUS) has been shown to accelerate cell proliferation and tissue healing in both animal models and clinical trials. However, details of the clinical effects of LIPUS have not been well characterized. The aim of this study was to investigate the effect of LIPUS on mitogen-activated protein kinase (MAPK) activation in rat articular chondrocytes. Design: Cross-sectional study. Methods: Chondrocyte were cultured in six well cell culture plates for 72 hours at $37^{\circ}C$ with 5% $CO_2$, and then exposed to LIPUS at 1.5 MHz frequency and $30-mW/cm^2$ power. Changes in chondrocyte activities were evaluated in response to oxydative stress in dose-dependent (0 and 300 uM) and time-dependent (0-24 hr) manner. The cell viability were analyzed using MTT [3-(4.5-dimethylthiazol-2-yl)-2.5 diphenyltetrazolium bromide]. The expression of p38 MAPK was measured using western blotting. Results: Oxidative stress was induced in rat chondrocytes using hydrogen peroxide ($H_2O_2$). The cell viability was decreased in chondrocytes after the $H_2O_2$ dose and time-dependent treatment. The p38 MAPK phosphorylation occurred at a significantly increased rate after $H_2O_2$ treated (p<0.05). Expression of p38 MAPK was decreased in the p38 inhibitor groups compared with the oxidative stress-induced chondrocyte damage via the p38 MAPK signaling pathways (p<0.05). Conclusions: It could be concluded that LIPUS can inhibit oxidative stress-induced chondrocyte damage via the p38 MAPK signaling pathways.

• Journal of Applied Biological Chemistry
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• v.64 no.3
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• pp.277-284
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• 2021

The emergence and rapid spread of the potentially fatal coronavirus disease 2019, caused due to infection by severe acute respiratory syndrome coronavirus-2, has led to worldwide interest in developing functional bioactive ingredients that act as immunomodulatory agents. In this study, we aimed to characterize Carica papaya extract and explore its potential as an immunomodulator by performing in vitro cell screening. Papaya leaf water extract (PLW) was found to significantly increase the levels of nitric oxide (NO) and prostaglandin E₂ (PGE₂) by upregulating inducible nitric oxide synthase and cyclo-oxygenase-2 activity, respectively. Additionally, PLW increased the production of tumor necrosis factor-α and interleukin 1β in RAW 264.7 cells. Furthermore, PLW activated the expression of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) but not that of p38 mitogen-activated protein kinase. These results indicate that PLW increased the production of NO, PGE₂, and pro-inflammatory cytokines by activating the JNK and ERK pathways in macrophages, thus demonstrating immunomodulatory properties. Finally, high-performance liquid chromatography fingerprint analysis indicated the presence of rutin, narirutin, and ρ-coumaric acid in PLW (6.30, 119.76, and 47.25 ppm, respectively). Treating cells with these compounds at non-toxic concentrations had no effect on NO production. Taken together, these results suggest that PLW may have potential as an immunity-enhancing supplement.

• Food Science of Animal Resources
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• v.42 no.1
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• pp.84-97
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• 2022

We evaluated the anti-biofilm formation and anti-inflammatory activity of Hovenia monofloral honey (HMH) against Enterococcus faecalis. Co-culture of HMH with E. faecalis attenuated the biofilm formation of E. faecalis on a polystyrene surface. In addition, HMH effectively eradicated the established E. faecalis biofilm. HMH significantly attenuated E. faecalis growth but did not affect the production of extracellular polymeric substances on E. faecalis, indicating that reduction of E. faecalis biofilm is a result of HMH-mediated killing of E. faecalis. Furthermore, we found that HMH can effectively attenuate E. faecalis-induced expression of a proinflammatory interleukin-8 (IL- 8) in HT-29 cells. Interestingly, treatment of HMH significantly attenuated the E. faecalis-mediated expression of Toll-like receptor-2 (TLR-2) and its adaptor molecules, myeloid differentiation primary response 88 (MyD88), in HT-29 cells. In addition, E. faecalis-induced mitogen-activated protein kinases (MAPKs) phosphorylation was significantly attenuated by HMH administration. Furthermore, HMH-mediated antiinflammatory efficacy (0.2 mg/mL of HMHs) had an equal extent of inhibitory efficacy as 5 μM of MyD88 inhibitor to attenuate E. faecalis-mediated IL-8 expression in HT-29 cells. These results suggest that HMH could effectively inhibit E. faecalis-mediated gastrointestinal inflammation through regulating the TLR-2/MyD88/MAPKs signaling pathways. Collectively, our data suggest that HMH could be developed as a potential natural agent to control E. faecalis-mediated biofilm formation and inflammation.