• YAKHAK HOEJI
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• v.51 no.1
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• pp.44-50
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• 2007

Acute septic shock is one of inflammatory diseases mediated by pro-inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$. In this study, we examined the pathological difference and mechanism of lipopolysaccharides isolated from E. coli (E-LPS) or S. abortus (S-LPS) on inducing acute septic shock in ICR mouse. All mice were died by intraperitoneal treatment of S-LPS with 0.75 mg/kg, whereas E-LPS treated with even 3 mg/kg only showed 30% of mice lethal, indicating that S-LPS may be more feasible in triggering a strong septic shock condition. The secretion pattern of TNF-${\alpha}$, a critical pro-inflammatory cytokine in septic shock condition, was also distinct between E-LPS- and S-LPS-treated groups. Thus, S-LPS strikingly increased serum level of TNF-${\alpha}$ (6 ng/ml) at 1 h, while E-LPS just displayed at 2 ng/ml level. However the interaction of S-LPS with LPS receptor toll like receptor (TLR)-4, was not stronger than that of E-LPS, according to experiments with macrophage cell line RAW264.7 cells. Thus, E-LPS rather than S-LPS strongly enhanced the production of TNF-${\alpha}$. Interestingly, S-LPS more strongly up-regulated splenocyte proliferation, compared to E-LPS group, whereas there was no difference between S- or E-LPS treated groups in proliferation of Balb/c- or C57BL/6-originated splenic lymphocytes. Therefore, our data suggest that S-LPS is a more active endotoxin and that the strong septic shock-inducing effect of S-LPS seems due to the enhancement of early TNF-${\alpha}$ production and S-LPS-sensitive lymphocyte proliferation.

• YAKHAK HOEJI
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• v.54 no.2
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• pp.91-96
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• 2010

Berberine, an isoquinoline alkaloid, has a wide range of pharmacological effects, including anti-inflammation. It has been reported that berberine inhibits experimental colitis through inhibition of IL-8, and that inhibitory effect of berberine on inflammatory cytokine expression is mediated through peroxisome proliferator activated receptor (PPAR)-$\gamma$. In this study, we examined the effects and action mechanism of berberine on the tumor necrosis factor (TNF)-$\alpha$-induced monocyte adhesion to HT29 human colonic epithelial cells, which is commonly used as an in vitro model of inflammatory bowel disease (IBD). Berberine significantly inhibited the TNF-$\alpha$-induced monocyte adhesion to HT29, which is similar to the effect of PDTC, a nuclear factor (NF)-$\kappa$B inhibitor. However, ciglitazone and GW, the ligands of PPAR-$\gamma$, did not suppress the TNF-$\alpha$-induced monocyte adhesion to HT29 cells. In addition, TNF-$\alpha$-induced chemokine expression and NF-$\kappa$B transcriptional activity were significantly inhibited by berberine in a concentration-dependent manner. The results suggest that inhibitory effect of berberine on colitis is mediated through suppression of NF-$\kappa$B and NF-$\kappa$B-dependent chemokine expression.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.23-29
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• 2005

Background: Interleukin-7 receptor (IL-7R) ${\alpha}$-deficient mice have small numbers of B cells and ${\alpha}{\beta}$T cells in periphery, they totally lack ${\gamma}{\delta}$T cells. In addition, the V-J recombination and transcription of TCR ${\gamma}$ genes is also severely impaired in IL-7R ${\alpha}$-deficient mice. Stat5, a signaling molecule of the IL-7R, induces germline transcription in the TCR ${\gamma}$ locus, and promotes V-J recombination and ${\gamma}{\delta}$T cell development. However, the roles for IL-7R signaling pathway in thymic or extrathymic ${\gamma}{\delta}$T cell development are largely unknown. Methods: To clarify the role of the IL-7 receptor in proliferation and survival of ${\gamma}{\delta}$T cells, we introduced the TCR ${\gamma}{\delta}$ transgene, $V_{{\gamma}2}/V{\delta}_5$, into IL-7R ${\alpha}$-deficient mice, and investigated the development of ${\gamma}{\delta}$T cells. Results: We found that $V_{{\gamma}2}/V{\delta}_5$ transgene restored ${\gamma}{\delta}$T cells in the epithelium of the small intestine (IEL) but not in the thymus and the spleen. Further addition of a bcl-2 transgene resulted in partial recovery of ${\gamma}{\delta}$T cells in the thymus and the spleen of these mice. Conclusion: Taken together, this study revealed that the IL-7R ${\alpha}$ is indispensable for proliferation and survival mainly in thymic ${\gamma}{\delta}$T cell development.

• The Journal of Korean Medicine
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• v.22 no.1
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• pp.63-77
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• 2001

Objectives : In acute stage of CVA, many patients experience Bugibultong as a symptom. Daesiho-tang is one of the most useful prescriptions for constipated stroke patients. This study investigated the effects of Daesiho-tang extracts on hypoxic E18 cortical neuroblast. Methods : To evaluate the effect of Daesiho-tang extracts on enuronal death caused by hypocia the neuronal viability and protein expressions of NMDA receptor subunits, ${\alpha}CaMK$ II PDE2 PSD95 densin-180, $eEF-l{\alpha}$ and GFAP were investigated. Results : We guessed that Daesiho-tang extracts worked to protect against cell damage through effecting on the protein expression of PSD(post synatpic density), especially increase of ${\alpha}CaMK$ II, $eEF-l{\alpha}$ PDE2, PSD95 and densin-180 Conclusions : According to the above results, it is supposed that Daesiho-tang is clinically applicable to stroke patients in the acute stage.

• Journal of Life Science
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• v.23 no.5
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• pp.650-656
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• 2013

Endothelial protein C receptor (EPCR) plays a pivotal role in augmenting Protein C activation through the thrombin-thrombomodulin complex. EPCR activity is markedly changed by ectodomain cleavage and released as the soluble protein (sEPCR). EPCR shedding is mediated by tumor necrosis factor-${\alpha}$ converting enzyme (TACE). Lycopene found in tomatoes and tomato products has anti-oxidant, anti- cancer and anti-inflammatory effects. However, little is known about the effects of lycopene on EPCR shedding. We investigated this issue by monitoring the effects of lycopene on the phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and on the cecal ligation and puncture (CLP)-mediated EPCR shedding. Data showed that lycopene potently inhibited the PMA, TNF-${\alpha}$, IL-$1{\beta}$ and CLP-induced EPCR shedding by suppressing TACE expression. Furthermore, lycopene reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2 and c-Jun N-terminal kinase (JNK). Given these results, lycopene should be viewed as a candidate therapeutic agent for the treatment of various severe vascular inflammatory diseases via inhibition of the EPCR shedding.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.527-538
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• 2019

Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.20 no.4
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• pp.334-340
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• 1998

Stimulatory effects of epidermal growth factor (EGF) and transforming growth $factor-{\alpha}$($TGF-{\alpha}$) on the growth of squamous cancer cell lines established from human oral cancer tissue with moderate differentiation were studied in vitro. After culturing in serum-free media for 24 hours, growth factors-EGF only, $TGF-{\alpha}$ only and EGF, $TGF-{\alpha}$ together-were added to the media and numbers of cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and compared with the control at 96, 144 hours. Each of EGF and $TGF-{\alpha}$ showed statistically significant stimulatory effects on the growth of cells respectively. Dose-dependent relationship of the stimulatory effects were not clearly demonstrated. The effects of EGF were higher than those of $TGF-{\alpha}$ and combinative administration showed higher effects than those of single uses. In conclusion, EGF may play an important and major role in differentiation and growth of human oral squamous cancer cells. $TGF-{\alpha}$, produced from cells activated by EGF, also can stimulate the cell growth and could be an alternative ligand for EGF receptor.

• Korean Journal of Veterinary Research
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• v.33 no.2
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• pp.211-216
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• 1993

To elucidate the action of the cholinergic and ${\alpha}_2$-adrenergic nerve on the isolated ileal smooth muscle of the dog, effect a of electrical field stimulation were investigated on the pretreatment of the physostigmine; cholinestrase inhibitor, yohimbine; ${\alpha}_2$-adrenoceptor blocker, atropine ; cholinergic receptor blocker and phentolamine; non-selective $\alpha$-adrenoceptor blocker from physiograph. 1. The contractile response induced by electrical field stimulation was the frequency (2-40 Hz)-dependent manner. 2. The contractile response induced by electrical field stimulation was markedly increased by the pretreatment of physostigmine$(1{\mu}M)$; cholinestrase inhibitor. 3. The contractile response induced by electrical field stimulation was increased by the pretreatment of yohimbine$(1{\mu}M)$; ${\alpha}_2$-adrenoceptor blocker. These finding suggest that it was powerful excitatory action by cholinergic nerve and inhibitory action by ${\alpha}_2$-adrenergic nerve on ileal smooth muscle of the dog.

• Molecules and Cells
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• v.39 no.2
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• pp.87-95
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• 2016

Sirt1 is the most prominent and extensively studied member of sirtuins, the family of mammalian class III histone deacetylases heavily implicated in health span and longevity. Although primarily a nuclear protein, Sirt1's deacetylation of Peroxisome proliferator-activated receptor Gamma Coactivator-$1{\alpha}$ (PGC-$1{\alpha}$) has been extensively implicated in metabolic control and mitochondrial biogenesis, which was proposed to partially underlie Sirt1's role in caloric restriction and impacts on longevity. The notion of Sirt1's regulation of PGC-$1{\alpha}$ activity and its role in mitochondrial biogenesis has, however, been controversial. Interestingly, Sirt1 also appears to be important for the turnover of defective mitochondria by mitophagy. I discuss here evidences for Sirt1's regulation of mitochondrial biogenesis and turnover, in relation to PGC-$1{\alpha}$ deacetylation and various aspects of cellular physiology and disease.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.347-354
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• 2014

Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for $hER{\alpha}$ and $hER{\beta}$ with $IC_{50}$ values of $1.20{\times}10^{-7}$ g/ml and $1.00{\times}10^{-7}$ g/ml, respectively. LNE induced $17{\beta}$-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on $hER{\alpha}$ and ${\beta}$ than other fractions. Our results indicate that LNE had higher binding affinities for $hER{\beta}$ than $hER{\alpha}$, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.