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ABSTRACT: We investigated the effects of orally administered probiotic bacteria (Lactobacillus species) as allergic immune modulators in ovalbumin (OVA)-sensitized mice. BALB/c mice were intraperitoneally injected with OVA twice at a 2-week interval for allergy sensitization. The mice were then orally administered Lactobacillus casei YIT9029 (L1), L. casei HY7201 (L2), L. brevis HY7401 (L3), or L. plantarum HY20301 (L4) every 2 days for 3 weeks. Total IgE levels significantly decreased in sera of L3-administered mice but increased in the other groups. OVA-specific IgE levels decreased slightly in sera of mice administered L1, L3, and L4 but increased significantly in L2-administered mice. In passive cutaneous anaphylaxis (PCA) using sera from administered mice, only the L3-administered group showed reaction inhibition. High expression of TLR-2 with interferon (IFN)-gamma stimulation on peripheral blood mononuclear cells occurred in L3- or L4-administered mice. Th1 cytokines, including IFN-gamma and interleukin (IL)- 12, increased in splenocytes of L3-administered mice; however, IL-4 decreased in L1- and L4-administered groups; IL-5 decreased in all experimental groups. IL-6 decreased in the L3-administered group; and IL-10 decreased in L1-, L2-, and L3-administered groups. L3 induced antiallergic effects by increasing Th1 cytokines, decreasing Th2 cytokines, and inhibiting the PCA reaction, whereas L2 administration increased allergic effects.
Journal of Microbiology and Biotechnology 05/2013; 23(5):724-30. · 1.38 Impact Factor
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ABSTRACT: Indole-3-carbinol (I3C) and indole[3,2-b] carbazole (ICZ) are major bioactive food components in cruciferous vegetables. Although previous studies have demonstrated the anticancer activity of I3C and ICZ in various types of cancer cells, the manner in which indole compounds regulate migration or related epithelial-to-mesenchymal transitions (EMT) has yet to be determined. In this study, we investigated the effects of I3C and ICZ on migration using breast cancer cells (MCF-7 and MDA-MB231). Pre‑treatment with I3C and ICZ significantly inhibited the migration of breast cancer cells without cytotoxicity, as measured by monolayer scratch assay. In addition, I3C and ICZ decreased vimentin (a mesenchymal marker) and focal adhesion kinase (FAK) mRNA expression, while increasing E-cadherin (an epithelial marker) expression. Matrix metalloproteinase (MMP)-2 and -9 activity was also reduced by I3C and ICZ. Taken together, we propose that I3C and ICZ pre‑treatment inhibits the migration of breast cancer cells through suppression of the EMT process and reduced MMP activity by repressing FAK expression. Our findings suggested that I3C and ICZ are potential compounds for inhibition of breast cancer cell migration.
Molecular Medicine Reports 11/2012; · 0.42 Impact Factor
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ABSTRACT: Cardiac involvement has been reported in as many as 45-55% of patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS), and significant cardiac morbidity is reported in 6-7% of HIV patients. We investigated the inhibitory effects of isothiocyanates (ITCs) on heart dysfunction and mortality by regulating apoptosis in the left ventricle of the heart in a murine AIDS model. Mice were divided into six groups: an uninfected group, an untreated LP-BM5 retrovirus-infected group, and four LP-BM5 retrovirus-infected groups treated with one of four ITCs (sulforaphane [SUL], indolo[3,2-b]carbazole, benzyl isothiocyanate [BITC], or phenethyl isothiocyanate [PEITC]). After 16 weeks, the median survival time of the LP-BM5 retrovirus-infected mice was 87 days, whereas that of the uninfected control group and all ITC treatment groups was over 112 days. SUL, PEITC, and BITC significantly inhibited apoptosis in the left ventricle by increasing the Bcl-2/Bax ratio compared with LP-BM5-infected mice. In addition, SUL and PEITC suppressed inducible nitric oxide synthase (iNOS) expression at both the mRNA and protein levels in the left ventricle of heart tissue infected with the LP-BM5 retrovirus by inactivating cytoplasmic nuclear factor κB (NF-κB). In conclusion, LP-BM5 retrovirus infection was related to survival of murine AIDS mice, and NF-κB-mediated iNOS expression may be an important mediator of left ventricle dysfunction of the heart. Furthermore, certain ITCs may have the potential to improve AIDS-related heart dysfunction due to their inhibition of apoptosis by decreasing iNOS and Bax expression through suppression of NF-κB.
Journal of medicinal food 09/2012; 15(9):781-7. · 1.39 Impact Factor
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ABSTRACT: Pasteurella multocida serogroup D, producing P. multocida toxin (PMT), is a causative pathogen of progressive atrophic rhinitis (PAR) in swine. To evaluate the protective immunity and vaccination efficacy of the truncated form of PMT, a C-terminal form of recombinant PMT (designated PMT2.3; amino acid residues 505 to 1285 of PMT) was expressed in an Escherichia coli expression system, and the humoral and cellular immune responses to PMT2.3 were investigated. PMT2.3 vaccination in mice led to high levels of the anti-PMT antibody with a high neutralizing antibody titer. PMT2.3 also induced a cellular immune response to PMT, as demonstrated by the lymphocyte proliferation assay. Furthermore, strong protection against a homologous challenge with P. multocida was also observed in mice vaccinated with PMT2.3. In PMT2.3 vaccination in swine, high levels of serum antibody titers were observed in offspring from sows vaccinated with PMT2.3. Offspring from sows vaccinated with PMT2.3 or toxoid showed a good growth performance as depicted by mean body weight at the time of sacrifice, as well as in average daily gain in the postweaning period. Low levels of pathological lesions in turbinate atrophy and pneumonia were also observed in these offspring. Therefore, we consider PMT2.3--in the truncated and nontoxic recombinant PMT form--to be an attractive candidate for a subunit vaccine against PAR induced by P. multocida infection.
Clinical and vaccine immunology: CVI 07/2012; 19(9):1526-31. · 2.37 Impact Factor
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ABSTRACT: Oral administration of immunoglobulin in the colostrum or egg yolk has been considered an effective tool for preventing enterobacterial infection via passive immunization. During this process, the transmission and residence of the active immunoglobulin are the most important conditions for successful protection. We investigated the stability of encapsulated colostrum and egg yolk immunoglobulin for the effective transmission of immunoglobulin in the gastrointestinal (GI) tract. First, we measured GI transit time. Contrast media passed through and reached the stomach within 10 min, the small intestine within 3.5 h, and the cecum within 5 h. Both the encapsulated colostrum containing anti-hepatitis A virus (HAV) antibody (IgG) and egg yolk with anti-rotavirus antibody (IgY) showed lower antibody activity than the non-encapsulated colostrum did in the stomach after administration; however, significantly higher antibody activities were observed in the encapsulated groups than in the non-encapsulated groups in the small intestine 3.5 h after the administration. In the large intestine, the antibody activities of the encapsulated groups were maintained or slightly increased in a time-dependent manner; however, the titers of each non-capsulated control were as low as the negative controls. Therefore, this encapsulation is considered a useful tool for the delivery of active antibody through the GI tract.
Journal of immunological methods 06/2012; 384(1-2):143-7. · 2.35 Impact Factor
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ABSTRACT: Bovine spongiform encephalopathy (BSE) is one of the fatal neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs) caused by infectious prion proteins. Genetic variations correlated with susceptibility or resistance to TSE in humans and sheep have not been reported for bovine strains including those from Holstein, Jersey, and Japanese Black cattle. Here, we investigated bovine prion protein gene (PRNP) variations in Hanwoo cattle [Bos (B.) taurus coreanae], a native breed in Korea. We identified mutations and polymorphisms in the coding region of PRNP, determined their frequency, and evaluated their significance. We identified four synonymous polymorphisms and two non-synonymous mutations in PRNP, but found no novel polymorphisms. The sequence and number of octapeptide repeats were completely conserved, and the haplotype frequency of the coding region was similar to that of other B. taurus strains. When we examined the 23-bp and 12-bp insertion/deletion (indel) polymorphisms in the non-coding region of PRNP, Hanwoo cattle had a lower deletion allele and 23-bp del/12-bp del haplotype frequency than healthy and BSE-affected animals of other strains. Thus, Hanwoo are seemingly less susceptible to BSE than other strains due to the 23-bp and 12-bp indel polymorphisms.
Journal of veterinary science (Suwŏn-si, Korea) 06/2012; 13(2):127-37. · 0.89 Impact Factor
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ABSTRACT: An antioxidative compound with effective exercise-enhancing potential was isolated from the ethanolic extract of Pseudosasa japonica leaves. The ethanolic extract was partitioned in the order of hexane, chloroform, ethyl acetate, and water. Of the 4 fractions,
the ethyl acetate-fraction (PJE-E) showed profound scavenging activity on superoxide anion- and ABTs cation radicals. Thin
layer chromatography (TLC) and high performance liquid chromatography (HPLC) were conducted to isolate a compound with antioxidative
activity on exercise endurance capacity from the PJE-E. The structure of the resulting compound was identified as ferulic
acid by 1H/13C nuclear magnetic resonance (NMR). This ferulic acid was orally administered to mice for 18 days and its effect on exercise
endurance capacity was investigated using an adjustablecurrent water pool. Compared to the control group, a 1.8 fold increase
in swimming time was observed in the ferulic acid-administered mice. Results indicate that ferulic acid from P. japonica leaves might contribute to the potent exercise-enhancing effect.
Keywords
Pseudosasa japonica
-antioxidant-exercise endurance capacity-ferulic acid
Food science and biotechnology 04/2012; 19(2):571-574. · 0.49 Impact Factor
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ABSTRACT: In this study, we demonstrate that a bokbunja (Rubus coreanus) ethanol extract (RCE) exhibits the strong histone acetyltransferase (HAT) inhibitory activity, and shows specificity against
the p300 HAT enzyme. RCE specifically inhibited p300 acetyltransferase activities with an IC50 of approximately 70 μg/mL, but did not inhibit other epigenetic enzymes. We found that RCE inhibited agonist-dependent androgen
receptor (AR) acetylation and suppressed androgen-induced AR transcriptional activity. RCE treatment also decreased the enhancement
of AR transcriptional activity caused by p300 overexpression, and combined treatment with RCE potentiated the activity of
the AR antagonist flutamide. Finally, RCE treatment reduced the growth of LNCaP human prostate cancer cells via inhibition
of cyclin D1 and cyclin E expression, and concomitantly induced apoptosis. Collectively, our results suggest that therapeutic
targeting of AR acetylation by HATi could lead to a new class of antagonists for the treatment of prostate cancer.
Keywords
bokbunja
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Rubus coreanus
–histone acetyltransferase–androgen receptor–prostate cancer
Food science and biotechnology 04/2012; 19(6):1503-1511. · 0.49 Impact Factor
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ABSTRACT: Hepatoprotective effects of loquat (Eriobotrya japonica) leaves were investigated in HepG2 cells overexpressing CYP2E1. When compared to cells treated with 200 mM ethanol alone,
a concentration-dependent increase in cell viability was observed in the cells pretreated with 40 and 80 μg/mL of 5% ethanol
extract (EJE) of loquat leaves (23 and 36%, respectively). Also, pretreatment with EJE lead to a decrease in intracellular
reactive oxygen species formation and an increase in hepatic antioxidant activity. These results suggest that EJE attenuates
oxidative stress by improving antioxidative potentials, which contribute to this herb’s protective profile against ethanol-induced
toxicity in vitro.
Keywordsloquat-HepG2/2E1-hepatoprotection-oxidative stress-antioxidation
Food science and biotechnology 04/2012; 19(4):1093-1096. · 0.49 Impact Factor
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ABSTRACT: Manipulating acetylation status of key gene targets is likely to be crucial for effective cancer therapy. In this study, we utilized green tea catechins, epicatechin (EC), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG) to examine the regulation of androgen receptor acetylation in androgen-dependent prostate cancer cells by histone acetyl-transferase (HAT) activity. EC, EGC and EGCG induced prostate cancer cell death, suppressed agonist-dependent androgen receptor (AR) activation and AR-regulated gene transcription. These results demonstrated a similar tendency to HAT inhibitory activities; EGCG>EGC>EC. The strongest HAT inhibitor among them, EGCG (50 µM), downregulated AR acetylation and finally, AR protein translocation to nucleus from the cytoplasmic compartment was effectively inhibited in the presence of the agonist. These results suggest another mechanism to develop effective therapeutics based on green tea catechins.
International Journal of Molecular Medicine 04/2012; 30(1):69-74. · 1.98 Impact Factor
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Donghyuck Bae,
Heejin Seol,
Ho-Geun Yoon,
Ju-Ryun Na,
Kyonyeo Oh,
Chul Yung Choi,
Dong-wook Lee,
Woojin Jun,
Kwang Youl Lee, Jeongmin Lee,
Kwontack Hwang,
Yoo-Hyun Lee,
Sunoh Kim
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ABSTRACT: Chamaecyparis obtusa Sieb. & Zucc., Endlicher (Cupressaceae) forest bathing or aromatherapy has been shown in various studies to have biological functions such as anticancer, antiallergies, antiinflammatory, and antioxidant activity. However, no reports exist on the pharmacological or biological activities of the essential oil of C. obtusa (EOCO) or its effects on central nervous system.
The aggregation and formation of β-amyloid peptides (Aβ) into fibrils are central events in the pathogenesis of Alzheimer's disease (AD), and overproduction and aggregation of Aβ into oligomers have been known to trigger neurotoxicity. In this study, we investigated the effects of inhaled EOCO on cognitive function and neuronal apoptosis in rats intrahippocampally injected with Aβ.
To model AD, 4 μg of aggregated Aβ was injected into the hippocampus. To test the effects of EOCO, behavioral performance in the Morris water maze was tested 4 days after injection. After behavioral testing, brain sections were prepared for TTC staining and TUNEL assay. Results: Inhaled EOCO protected spatial learning and memory from the impairments induced by Aβ(1-40) injection. In addition, the behavioral deficits accompanying Aβ(1-40)-induced AD were attenuated by inhalation of EOCO. Furthermore, acetylcholinesterase (AChE) activity and neuronal apoptosis were significantly inhibited in rats treated with Aβ(1-40) and EOCO compared to rats treated only with Aβ(1-40).
EOCO suppressed both AD-related neuronal cell apoptosis and AD-related dysfunction of the memory system. Thus, the results of this study support EOCO as a candidate drug for the treatment of AD.
Pharmaceutical Biology 04/2012; 50(7):900-10. · 0.88 Impact Factor
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ABSTRACT: We examined the anti-obesity effect of fermented Curcuma longa L. (turmeric) standardised ethanol extract (FTE) in the C57BL/6J ob/ob mouse model. Mice were fed a chow diet containing FTE (0, 200, or 500 mg kg⁻¹ body weight) for 9 weeks.
Supplementation with FTE significantly reduced body weight gain and retroperitoneal and epididymal adipose tissue weights compared to the ob/ob control group. Additionally, total cholesterol and triglyceride levels in serum and liver were significantly decreased in FTE-200 and FTE-500 groups when compared to those of the ob/ob control group, whereas the high-density lipoprotein-cholesterol level was significantly increased. The levels of serum adiponectin as well as mRNA expression of lipases, such as hormone sensitive lipase and adipose triglyceride lipase, were clearly increased. In primary adipocytes of C57BL/6J mice, FTE treatment caused a significant increase glycerol release and hormone sensitive lipase levels and decreased perilipin A levels.
These results suggest that supplementation of FTE has potent anti-obesity effects by controlling body weight, fat mass, serum lipids, and hepatic lipids. Moreover, FTE could be considered a potential resource for the treatment of obesity through its promotion of lipolysis via the protein kinase A pathway.
Journal of the Science of Food and Agriculture 01/2012; 92(9):1833-40. · 1.44 Impact Factor
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ABSTRACT: We examined the biological effect of gallic acid (GA) as a nuclear factor (NF)-κB acetyltransferase inhibitor on microglial-mediated β-amyloid neurotoxicity and restorative effects on the Aβ-induced cognitive dysfunction.
The protective effects of GA on the survival of neuronal cells were assessed with an MTT assay and a co-culture system. For the co-culture experiments, both BV-2 and primary microglia cells were treated with GA prior to Aβ stimulation, and conditioned media were transferred to Neuro-2A cells. The mRNA and protein levels of inflammatory cytokines in both microglia and Neuro-2A cells were assessed with real-time polymerase chain reaction and western blotting. Inhibition of nuclear factor kappa B (NF-κB) acetylation with GA treatment resulted in reduced cytokine production in microglia cells and protection of neuronal cells from Aβ-induced neurotoxicity. Furthermore, we observed a restorative effect of GA on Aβ-induced cognitive dysfunction in mice with Y-maze and passive avoidance tests. Finally, we found that GA treatment efficiently blocked neuronal cell death by downregulating the expression of cytokines and the in vivo levels of NF-κB acetylation.
These results suggest that selective inhibition of NF-κB acetylation by the histone acetyltransferase inhibitor GA is a possible therapeutic approach for alleviating the inflammatory progression of Alzheimer disease.
Molecular Nutrition & Food Research 12/2011; 55(12):1798-808. · 4.30 Impact Factor
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ABSTRACT: The purpose of this study was to determine the effect of isothiocyanates (ITCs) in delaying the progression of the murine immunodeficiency virus to murine AIDS, resulting in increased life span. Furthermore, we investigated the role of ITCs in modulating immune dysfunction caused by LP-BM5 retrovirus infection. Among the tested ITCs, oral administration of sulforaphane (SUL), benzyl isothiocyante (BITC), and phenethyl isothiocyanate (PEITC) showed the inhibition of premature death caused by LP-BM5 retrovirus infection, while indolo[3,2-b] carbazole (ICZ) and indole-3-carbinol (I3C) did not delay the progress of the LP-BM5 retrovirus to murine AIDS. Inhibition of premature death by BITC, PEITC, and SUL could be explained by restoration of the immune system and down regulation of free radicals. Dysfunction of T and B cell mitogenesis caused by retrovirus infection in primary cultured splenocytes has been partially recovered with administration of BITC, PEITC, and SUL. There was a shift from imbalanced cytokine production (increased Th2 and decreased Th1 cell cytokine production) into balanced Th1/Th2 cell secretion of cytokines under administration of these ITCs during the development of murine AIDS. Hepatic vitamin E level was significantly restored by administration of these ITCs, in accordance with reduced hepatic lipid peroxidation levels. This study suggests that certain types of ITCs have beneficial effects in preventing premature death during progression to murine AIDS by restoration of immune dysfunction and removal of excessive free radicals, implying that selective usage of ITCs would be helpful in retarding the progression from HIV infection to AIDS.
Bioscience Biotechnology and Biochemistry 07/2011; 75(7):1234-9. · 1.28 Impact Factor
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ABSTRACT: Histone acetyltransferase (HAT) inhibitors (HATi) isolated from dietary compounds have been shown to suppress inflammatory signaling, which contributes to rheumatoid arthritis. Here, we identified a novel HATi in Punica granatum L. known as delphinidin (DP). DP did not affect the activity of other epigenetic enzymes (histone deacetylase, histone methyltransferase, or sirtuin1). DP specifically inhibited the HAT activities of p300/CBP. It also inhibited p65 acetylation in MH7A cells, a human rheumatoid arthritis synovial cell line. DP-induced hypoacetylation was accompanied by cytosolic accumulation of p65 and nuclear localization of IKBα. Accordingly, DP treatment inhibited TNFα-stimulated increases in NF-κB function and expression of NF-κB target genes in these cells. Importantly, DP suppressed lipopolysaccharide-induced pro-inflammatory cytokine expression in Jurkat T lymphocytes, demonstrating that HATi efficiently suppresses cytokine-mediated immune responses. Together, these results show that the HATi activity of DP counters anti-inflammatory signaling by blocking p65 acetylation and that this compound may be useful in preventing inflammatory arthritis.
Biochemical and Biophysical Research Communications 06/2011; 410(3):581-6. · 2.48 Impact Factor
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ABSTRACT: The diagnosis of acute pyelonephritis (APN) is often difficult, as its clinical and biological manifestations are non-specific in children. If not treated quickly and adequately, however, APN may cause irreversible renal damage, possibly leading to hypertension and chronic renal failure. We were suspecting the diagnostic value of (99m)Tc-dimercaptosuccinic acid (DMSA) scan by experiences and so compared the results of DMSA scan to those of multi-detector row computed tomography (MDCT).
We retrospectively selected and analyzed 81 patients who were diagnosed as APN by MDCT during evaluation of their acute abdomen in emergency room and then received DMSA scan also for the diagnostic work-up of APN after admission. We evaluated the results of imaging studies and compared the diagnostic value of each method by age groups, <2 years (n=45) and ≥2 years (n=36).
Among total 81 patients with MDCT-proven APN. DMSA scan was diagnostic only in 55 children (68%), while the remaining 26 children (32%) showed false negative normal findings. These 26 patients were predominantly male with average age of 21 months and most of them, 19 (73.1%) were <2 years of age.
DMSA scan has obvious limitation compared to MDCT in depicting acute inflammatory lesions of kidney in children with APN, especially in early childhood less than 2 years of age. MDCT showed hidden lesions of APN, those were undetectable through DMSA scan in children.
Korean Journal of Pediatrics 05/2011; 54(5):212-8.
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ABSTRACT: The fatigue-alleviating effects on mice of Rubus coreanus were investigated by using an adjustable-current water pool. The mice were exhaustively exercised for 2 consecutive days, and those administered with the 80% ethanol extract (RCE) of R. coreanus displayed a lower reduction (20%) in swimming time on day 2 than the control group (41% reduction). RCE significantly prevented the depletion of hepatic antioxidants during exercise-induced fatigue. These results suggest that RCE alleviated fatigue by elevating the antioxidative potential.
Bioscience Biotechnology and Biochemistry 02/2011; 75(2):349-51. · 1.28 Impact Factor
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ABSTRACT: The generation of oxygen free radicals and oxidative damage is believed to be involved in the pathogenesis of neurodegenerative disorders. Eriobotrya japonica has been used to treat several diseases in East Asia. In this study, we investigated the protective effect of an E. japonica extract against Aβ peptide-induced oxidative stress. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay demonstrated that the E. japonica extract scavenged approximately 40% of DPPH radicals. Also, treatment of the E. japonica extract inhibited Aβ(1-42)-mediated neuronal cell death. Furthermore, treatment of E. japonica extract efficiently suppressed the increase in intracellular ROS triggered by the Aβ(1-42) peptide. Importantly, mice pre-treated with the E. japonica extract showed restoration of alternation behavior and reversal of Aβ(1-42)-induced memory impairment. Consequently, the E. japonica extract substantially inhibited the increase in lipid peroxidation and restored superoxide dismutase activity. These results suggest that E. japonica protects from oxidative stress and cognitive deficits induced by the Aβ peptide.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 12/2010; 49(4):780-4. · 2.99 Impact Factor
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ABSTRACT: Pasteurella multocida serogroup D strain, which produces P. multocida toxin (PMT), is a widespread and harmful pathogen of respiratory diseases such as pneumonia and progressive atrophic rhinitis (PAR) in swine. Vaccination has been considered the most desirable and effective approach for controlling the diseases caused by toxigenic P. multocida. To investigate the antigenicity and immunogenicity of partial fragments of recombinant PMT, recombinant proteins of the N-terminal (PMT-A), middle (PMT-B), Cterminal (PMT-C), and middle-C-terminal (PMT2.3) regions of PMT were successfully produced in an Escherichia coli expression system. The molecular masses of PMT-A, PMT-B, PMT-C, and PMT2.3 were ca. 53, 55, 35, and 84 kDa, respectively, purified by nickel-nitrilotriacetic acid (Ni-NTA) affinity column chromatography. All the recombinant proteins except for PMT-A showed immune responses to antisera obtained from a swine showing symptoms of PAR. Moreover, high titers of PMT-specific antibodies were raised from mice immunized with each of the recombinant proteins; however, the immunoreactivities of the antibodies to authentic PMT and heat-inactivated whole bacteria were different, respectively. In the protection study, the highest protection against homologous challenge was shown in the case of PMT2.3; relatively poor protections occurred for the other PMT fragments.
Journal of Microbiology and Biotechnology 12/2010; 20(12):1756-63. · 1.38 Impact Factor
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Han-Cheon Kim,
Kyung-Chul Choi,
Hyo-Kyoung Choi,
Hee-Bum Kang,
Mi-Jeong Kim,
Yoo-Hyun Lee,
Ok-Hee Lee, Jeongmin Lee,
Young Jun Kim,
Woojin Jun,
Jae-Wook Jeong,
Ho-Geun Yoon
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ABSTRACT: We identified CREB3 as a novel HDAC3-interacting protein in a yeast two-hybrid screen for HDAC3-interacting proteins. Among all class I HDACs, CREB3 specifically interacts with HDAC3, in vitro and in vivo. HDAC3 efficiently inhibited CREB3-enhanced NF-κB activation, whereas the other class I HDACs did not alter NF-κB-dependent promoter activities or the expression of NF-κB target genes. Importantly, both knock-down of CREB3 and overexpression of HDAC3 suppressed the transcriptional activation of the novel CREB3-regulated gene, CXCR4. Furthermore, CREB3 was shown to bind to the CRE element in the CXCR4 promoter and to activate the transcription of the CXCR4 gene by causing dissociation of HDAC3 and subsequently increasing histone acetylation. Importantly, both the depletion of HDAC3 and the overexpression of CREB3 substantially increased the migration of MDA-MB-231 metastatic breast cancer cells. Taken together, these findings suggest that HDAC3 selectively represses CREB3-mediated transcriptional activation and chemotactic signalling in human metastatic breast cancer cells.
Cellular and Molecular Life Sciences CMLS 10/2010; 67(20):3499-510. · 6.57 Impact Factor
