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Orientia tsutsugamushi Infection Induces $CD4^+$ T Cell Activation via Human Dendritic Cell Activity

  • Chu, Hyuk;Park, Sung-Moo;Cheon, In Su;Park, Mi-Yeoun;Shim, Byoung-Shik;Gil, Byoung-Cheol;Jeung, Woon Hee;Hwang, Kyu-Jam;Song, Ki-Duk;Hong, Kee-Jong;Song, Manki;Jeong, Hang-Jin;Han, Seung Hyun;Yun, Cheol-Heui
    • Journal of Microbiology and Biotechnology
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    • v.23 no.8
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    • pp.1159-1166
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    • 2013
  • Orientia tsutsugamushi, a gram-negative bacterium, causes severe acute febrile illness in humans. Despite this danger, the route of infection, infectivity, and protective mechanisms of the host's immune response to O. tsutsugamushi are unclear. Dendritic cells (DCs) are one of the most important cell types in bridging the innate and adaptive immune responses. In this study, we observed that O. tsutsugamushi infects and replicates in monocyte-derived DCs (MODCs). During infection and replication, the expressions of the cytokines IL-12 and TNF-${\alpha}$, as well as the co-stimulatory molecules CD80, CD83, CD86, and CD40, were increased in MODCs. When O. tsutsugamushi-treated MODCs were co-cultured with autologous $CD4^+$ T cells, they enhanced production of IFN-${\gamma}$, a major Th1 cytokine. Collectively, our results show that O. tsutsugamushi can replicate in MODCs and can simultaneously induce MODC maturation and increase proinflammatory cytokine levels in MODCs that subsequently activate $CD4^+$ T cells.

Surface-Displayed Porcine IFN-λ3 in Lactobacillus plantarum Inhibits Porcine Enteric Coronavirus Infection of Porcine Intestinal Epithelial Cells

  • Liu, Yong-Shi;Liu, Qiong;Jiang, Yan-Long;Yang, Wen-Tao;Huang, Hai-Bin;Shi, Chun-Wei;Yang, Gui-Lian;Wang, Chun-Feng
    • Journal of Microbiology and Biotechnology
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    • v.30 no.4
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    • pp.515-525
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    • 2020
  • Interferon (IFN)-λ plays an essential role in mucosal cells which exhibit strong antiviral activity. Lactobacillus plantarum (L. plantarum) has substantial application potential in the food and medical industries because of its probiotic properties. Alphacoronaviruses, especially porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), cause high morbidity and mortality in piglets resulting in economic loss. Co-infection by these two viruses is becoming increasingly frequent. Therefore, it is particularly important to develop a new drug to prevent diarrhea infected with mixed viruses in piglets. In this study, we first constructed an anchored expression vector with CWA (C-terminal cell wall anchor) on L. plantarum. Second, we constructed two recombinant L. plantarum strains that anchored IFN-λ3 via pgsA (N-terminal transmembrane anchor) and CWA. Third, we demonstrated that both recombinant strains possess strong antiviral effects against coronavirus infection in the intestinal porcine epithelial cell line J2 (IPEC-J2). However, recombinant L. plantarum with the CWA anchor exhibited a more powerful antiviral effect than recombinant L. plantarum with pgsA. Consistent with this finding, Lb.plantarum-pSIP-409-IFN-λ3-CWA enhanced the expression levels of IFN-stimulated genes (ISGs) (ISG15, OASL, and Mx1) in IPEC-J2 cells more than did recombinant Lb.plantarum-pSIP-409-pgsA'-IFN-λ3. Our study verifies that recombinant L. plantarum inhibits PEDV and TGEV infection in IPEC-J2 cells, which may offer great potential for use as a novel oral antiviral agent in therapeutic applications for combating porcine epidemic diarrhea and transmissible gastroenteritis. This study is the first to show that recombinant L. plantarum suppresses PEDV and TGEV infection of IPEC-J2 cells.

Effects of Glucuronic Acid Derivertives Isolated from Xylan an Antioxidative Defense System and Muscle Fatigue Recovery after Aerobic Exercise (Xylan으로부터 단리한 Glucuronic Acid의 유산소 운동 후 항산화 작총 및 근피로 회복효과)

  • 최향미;이수천;류승필;이인구;주길재;이순재
    • Journal of Nutrition and Health
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    • v.34 no.8
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    • pp.872-880
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    • 2001
  • The purpose of this study was to investigate the effects of glucuronic acid on antioxidative defense system and recovery of muscle fatigue in rat artier aerobic exercise. Sprague-Dawley male rats weighing 150 $\pm$ 10g were randomly assigned to one normal(N) group and three exercise training groups. Exercise training groups were classified into glucuronic acid free intubation group(T group), 250mg glucuronic acid/kg bw intubation group(TU group), and 500 mg glucuronic acid/kg bw intubation group(2TU group) according to glucuronic acid supplementation level. The glucuronic acids were administered to rats by oral intubation before exercise training. The experimental rats in exercise training groups(T, TU and 2TU) were exercised on glucuronic acid supplementation or rats in normal group were confined in cage for 4 weeks. And rats were sacrificed with an overdose of pentobarbital injection just after running. Liver xanthine oxidase(XOD) activities were not significantly different among four groups. The activity of superoxide dismutase(SOD) in T group was no significant difference from N group, but those of TU and 2TU groups were increased by 9% and 18%, respectively, compared with that of T group. Liver glutathione peroxidase(GSHpx) activites of T and TU groups showed a similar tendency to that of normal group, but increase 17% in 2TU group compared with normal group. The ratio of GSH/GSSG in liver of T group was lower than that of normal group, but those of TU and 2TU groups were a similar tendency to that of normal group. Contents of thiobarbituric acid reactive substance(TBARS) in T group was increased by 47%, compared with that of normal group but those of TU group and 2TU group were lower 27% and 35%, respectively, compared with that of T group. The contents of glycogen in soleus muscle significantly lower in all three trained exercise groups than that of normal group, but there were no significant differences among the trained exercise groups. Contents of hepatic glycogen in T group were decreased 27% compared with those of normal group while those of TU and 2TU groups were the same as normal group levels. The contents of serum lactic acid in T group were increased 240% of normal group, but hose of TU and 2TU groups were decreased 38%, 39%, respectively, by glucuronic acid supplementations, compared with that of T group. In conclusion, the effects of glucuronic acids in exercise training rats would appear to reduce peroxidation of tissue as an antioxidative defense mechanism and promote recovery of muscle fatigue.

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Apios americana Medik Extract Alleviates Lung Inflammation in Influenza Virus H1N1- and Endotoxin-Induced Acute Lung Injury

  • Sohn, Sung-Hwa;Lee, Sang-Yeon;Cui, Jun;Jang, Ho Hee;Kang, Tae-Hoon;Kim, Jong-Keun;Kim, In-Kyoung;Lee, Deuk-Ki;Choi, Seulgi;Yoon, Il-Sub;Chung, Ji-Woo;Nam, Jae-Hwan
    • Journal of Microbiology and Biotechnology
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    • v.25 no.12
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    • pp.2146-2152
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    • 2015
  • Apios americana Medik (hereinafter Apios) has been reported to treat diseases, including cancer, hypertension, obesity, and diabetes. The therapeutic effect of Apios is likely to be associated with its anti-inflammatory activity. This study was conducted to evaluate the protective effects of Apios in animal models of acute lung injury induced by lipopolysaccharide (LPS) or pandemic H1N1 2009 influenza A virus (H1N1). Mice were exposed to LPS or H1N1 for 2-4 days to induce acute lung injury. The treatment groups were administered Apios extracts via oral injection for 8 weeks before LPS treatment or H1N1 infection. To investigate the effects of Apios, we assessed the mice for in vivo effects of Apios on immune cell infiltration and the level of pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. After induction of acute lung injury, the numbers of neutrophils and total cells were lower in the Apios-treated groups than in the non-Apios-treated LPS and H1N1 groups. The Apios groups tended to have lower levels of tumor necrosis factor-a and interleukin-6 in BAL fluid. In addition, the histopathological changes in the lungs were markedly reduced in the Apios-treated groups. These data suggest that Apios treatment reduces LPS- and H1N1-induced lung inflammation. These protective effects of Apios suggest that it may have therapeutic potential in acute lung injury.

Transbilayer Effects of n-Alkanols on the Fluidity of Model Membranes of Total Lipids Extracted from Synaptosomal Plasma Membrane Vesicles (n-Alkanols가 소의 대뇌피질 Synaptosomal Plasma Membrane Vesicles로부터 추출 제제한 총지질 인공세포막 이중층간에 형성된 비대칭적 유동성에 미치는 비대칭적 영향)

  • Yun, Il;Kang, Jung-Sook
    • The Korean Journal of Pharmacology
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    • v.28 no.2
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    • pp.191-199
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    • 1992
  • Selective quenching of 1,6-diphenyl-1,3,5-hexatriene (DPH) by trinitrophenyl groups was utilized to examine the transbilayer fluidity asymmetry of model membranes of total lipids (SPMVTL) extracted from synaptosomal plasma membrane vesicles (SPMV). The polarization (P), anisotropy (r), limiting anisotropy $(r_{\infty})$, and order parameter (S) of DPH in the inner monolayer were 0.031, 0.025, 0.033, and 0.070, respectively, greater than calculated for the outer monolayer of SPMVTL. Selective quenching of DPH by trinitrophenyl groups was also utilized to examine the effects of n-alkanols on the individual monolayer structure of SPMVTL. n-Alkanols fluidized the hydrocarbon region of bulk SPMVTL, and the potencies of n-alkanols up to 1-nonanol increased with carbon chain length. It appears that the potencies in bilayer fluidization increase by 1 order of magnitude as the carbon chain length increases by two carbon atoms. The cut-off phenomenon was reached at 1-decanol, where further increase in hydrocarbon length resulted in a decrease in pharmacological activity. The n-alkanols had greater fluidizing effects on the outer monolayer as compared to the inner monolayer of SPMVTL, even though these selective effects tended to become weaker as carbon chain length increased. Thus, it has been proven that n-alkanols exhibit selective rather than nonselective fluidizing effects within transbilayer domains of SPMVTL.

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Induction of Heme Oxygenase-1 by Traditional Herb Mix Extract Improves MKN-74 Cell Survival and Reduces Stomach Bleeding in Rats by Ethanol and Aspirin in vivo

  • Kang, Young-Jin;Moon, Hyung-Suk;Kim, Hye-Jung;Seo, Han-Geuk;Lee, Jae-Heun;Chang, Ki-Churl
    • The Korean Journal of Physiology and Pharmacology
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    • v.11 no.2
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    • pp.65-70
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    • 2007
  • Chinese herb medicines have traditionally been used to treat or alleviate the symptom of various diseases. The rationale for use of certain herbs to certain disorder is now getting unveiled by modern technology. In the present study, we investigated whether herb mix extract(HMX), which is alleged to be useful for gastric ulcer, protects stomach from oxidative stress. Rats were allowed to normal diet with and without HMX (1, 5, 10 mg/kg) for 30 days. To induce gastric ulcer, ethanol (75%, 1.5 ml) or acidified aspirin (100 mg/kg in 0.2 N HCl) was administered by oral route in 24 h-fasted rats and examined the gastric ulceration(bleeding) by measuring the size 1 h after the treatment. Results indicated the area of gastric bleeding was significantly less in HMX fed rats than in normal diet fed ones, and it was dependent on the duration and amount of HMX. To investigate the underlying mechanism by which HMX protects stomach from oxidative stress, expression of enzymes like heme oxygenase (HO), cyclooxygenase (COX), and inducible nitric oxide (iNOS) were investigated in MKN-74 cells, where aspirin or H. pylori was introduced. The results were compared with RAW 264.7 cells to check if there's cell specificities exist. The expression of HO-1 but not COX-2, iNOS was significantly increased by HMX. Furthermore, HO-1 inhibitor, SnPP IX reduced the HO-1 activity and reversed the survival rate in HMX-treated MKN-74 cells. There's no difference between RAW 264.7 cells and MKN-74 cells. We, thus, concluded that HMX is beneficial for protection from oxidative injury, and induction of HO-1 by HMX in gastric cells is, at least, responsible for protection from oxidative stress such as ethanol, aspirin and possibly H. pylori infection.

Oxytocin produces thermal analgesia via vasopressin-1a receptor by modulating TRPV1 and potassium conductance in the dorsal root ganglion neurons

  • Han, Rafael Taeho;Kim, Han-Byul;Kim, Young-Beom;Choi, Kyungmin;Park, Gi Yeon;Lee, Pa Reum;Lee, JaeHee;Kim, Hye young;Park, Chul-Kyu;Kang, Youngnam;Oh, Seog Bae;Na, Heung Sik
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.2
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    • pp.173-182
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    • 2018
  • Recent studies have provided several lines of evidence that peripheral administration of oxytocin induces analgesia in human and rodents. However, the exact underlying mechanism of analgesia still remains elusive. In the present study, we aimed to identify which receptor could mediate the analgesic effect of intraperitoneal injection of oxytocin and its cellular mechanisms in thermal pain behavior. We found that oxytocin-induced analgesia could be reversed by $d(CH_2)_5[Tyr(Me)^2,Dab^5]$ AVP, a vasopressin-1a (V1a) receptor antagonist, but not by $desGly-NH_2-d(CH_2)_5[D-Tyr^2,Thr^4]OVT$, an oxytocin receptor antagonist. Single cell RT-PCR analysis revealed that V1a receptor, compared to oxytocin, vasopressin-1b and vasopressin-2 receptors, was more profoundly expressed in dorsal root ganglion (DRG) neurons and the expression of V1a receptor was predominant in transient receptor potential vanilloid 1 (TRPV1)-expressing DRG neurons. Fura-2 based calcium imaging experiments showed that capsaicin-induced calcium transient was significantly inhibited by oxytocin and that such inhibition was reversed by V1a receptor antagonist. Additionally, whole cell patch clamp recording demonstrated that oxytocin significantly increased potassium conductance via V1a receptor in DRG neurons. Taken together, our findings suggest that analgesic effects produced by peripheral administration of oxytocin were attributable to the activation of V1a receptor, resulting in reduction of TRPV1 activity and enhancement of potassium conductance in DRG neurons.

Immunomodulatory Effects of Aureobasidium pullulans SM-2001 Exopolymers on Cyclophosphamide-Treated Mice

  • Yoon, Hyun-Soo;Kim, Joo-Wan;Cho, Hyung-Rae;Moon, Seung-Bae;Shin, Hyun-Dong;Yang, Kun-Ju;Lee, Hyeung-Sik;Kwon, Young-Sam;Ku, Sae-Kwang
    • Journal of Microbiology and Biotechnology
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    • v.20 no.2
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    • pp.438-445
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    • 2010
  • The immunomodulatory effects of Aureohasidium pullulans SM-2001 exopolymers containing $\beta$-1,3/1,6-glucan were evaluated in cyclophosphamide (CPA)-treated mice. To induce immunosuppression, 150 and 110 mg/kg of CPA were intraperitoneally injected 3 days and 1 day, respectively, before beginning administration of the test material. Exopolymers were delivered subcutaneously or orally, four times, in a volume of 10 ml/kg at 12-h intervals beginning 24 h after the second CPA treatment. Changes in thymus and spleen weights, splenic amounts of tumor necrosis factor (TNF)-$\alpha$, interleukin (IL)-$1{\beta}$, and IL-10, and numbers of CD3+, CD4+, CD8+, and TNF-$\alpha+$ thymus and spleen cells were monitored in CPA-treated mice. As a result of CPA treatment, dramatic decreases in the number of CD3+, CD4+, CD8+, and TNF-$\alpha+$ cells were detected in the thymus and spleen, along with decreases in thymus and spleen weights. In addition, splenic TNF-$\alpha$, IL-$1{\beta}$, and IL-10 contents were also decreased on observation with flow cytometry. However, oral and subcutaneous treatments with exopolymers effectively reduced the immunosuppressive changes induced by CPA. Therefore, it is concluded that exopolymers of A. pullulans SM-2001 can effectively prevent immunosuppression through, at least partially, the recruitment of T cells and TNF-$\alpha+$ cells or enhancement of their activity, and can provide an effective component of prevention or treatment regimens for immunosuppression related to cancer, sepsis, and high-dose chemotherapy or radiotherapy.

Effects of Various Nootropic Candidates on the Impaired Acquisition of Ethanol-treated Rats in Step-through Test (에탄올 급성 투여로 유발된 학습획득 손상에 미치는 수종 뇌기능개선 후보 물질의 작용)

  • Lee Soon-Chul;Kim Eun-Joo;You Kwan-Hee;Kang Jong-Seong;Moon Yang-Sun
    • Journal of Ginseng Research
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    • v.23 no.2 s.54
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    • pp.115-121
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    • 1999
  • Effects of single and repeated administration of various nootropic candidates were examined on impaired acquisition by single oral administration of 3 g/kg ethanol (EtOH) in step through test. The inhibitory effect of EtOH on acquisition was significantly reduced by single picrotoxin, but not affected by diazepam, acetyl-L-carnitine and apomorphine. Single or repeated red ginseng total saponin and deprenyl, single piracetam, repeated N-methyl-D-glucamine, but not single or repeated protopanaxadiol, protopanaxatriol and centrophenoxine significantly ameliorated the impairment of acquisition by EtOH. On the other hand, the inhibitory effect of repeated red ginseng total saponin but not that of repeated N-methyl-D-Glucamine, was significantly blocked by pretreatment of $\alpha$-methyl-$\rho$-tyrosine, a inhibitor of catecholamine synthesis. Whereas, the inhibitory effect of repeated deprenyl on EtOH amnesia was exaggerated by $\alpha$-methyl-$\rho$-tyrosine. These results suggest that the amelioration processes of drugs on ethanol amnesia involve complex mechanism between the central GABAergic and dopaminergic neuronal activity in memory and learning, although the effects of repeated drugs administration are not yet clear.

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Anti-metastatic Effect on Cancer cell and Immune System Activation by Orally Administered Boyanghwano-tang (보양환오탕(補陽還五湯) 경구투여 후 면역 활성화에 의한 암 전이 억제 효과)

  • Kim, Jin-Hwan;Hwang, Deok-Sang;Lee, Jin-Moo;Lee, Chang-Hoon;Lee, Kyung-Sub;Jang, Jun-Bok
    • The Journal of Korean Obstetrics and Gynecology
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    • v.27 no.2
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    • pp.46-58
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    • 2014
  • Objectives: This study was designed to investigate intestinal immune system activation and anti-metastatic effect on cancer cells by orally administered extracts of Boyanghwano-tang. Methods: To observe immunomodulating effects of Boyanghwano-tang on Peyer's patch cells, we measured cytokines GM-CSF, IL-4. In addition to observing effects of Boyanghwano-tang on hematopoiesis, we measured proliferation of bone marrow cells mediated by Peyer's patch cells in vitro. IgA induction activated in intestinal content and serum was measured to observe the effect of orally administered Boyanghwano-tang on mucosal immune system. After administering ovalbumin (OVA) with Boyanghwano-tang, Proliferation of Peyer's patch cell was measured to investigate gut immunostimulatory effect. Anti-metastatic experiments were conducted in vivo mouse model by using colon 26-M3.1 carcinoma cell. Results: The amounts of GM-CSF and IL-4 in the culture supernatant of Peyer's patch cells were significantly increased compared to the control group. The proliferation of bone marrow cell was significantly up-regualted with Boyanghwano-tang. These results indicate that oral administration of Boyanghwano-tang enhances the secretion of hematopoietic growth factors such as GM-CSF and IL-4 from Peyer's patch cells, and these cytokines also act on modulator of bone marrow cell proliferation. After orally administering OVA with Boyanghwano-tang, IgA induction and Proliferation of peyer's patch cell was up-regulated with Boyanghwano-tang. These results means orally administered Boyanghwano-tang activates intestinal immune system and has an inhibitory effect on tumor metastasis. In addition, We found that orally administered Boyanghwano-tang significantly inhibited tumor metastasis in vivo. Conclusions: Orally administered Boyanghwano-tang appears to have considerable activity on the anti-metastasis by activation of immune system.