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Potent Activity (potent + activity)
Selected AbstractsSynthesis and bioactivity evaluation of 3-hydroxy-3-(phenylethynyl)indol-2-one analoguesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 2 2009Gang Chen A series of propargylic alcohol was synthesized by the addition of phenylacetylene to isatin and its N-substituted derivatives for the first time. This reaction involves activation of zinc reagent via coordination with carbonyl substrates that behave "ligand like." The bioactivities on protective effect on the apoptosis of PC12 cells induced by H2O2 and cytotoxicity against lung cancer A549 and P388 cell line of these compounds were investigated, and several compounds showed potent activities. J. Heterocyclic Chem., 46, 217 (2009). [source] Plasma-soluble Fas (APO-1, CD95) and soluble Fas ligand in immune thrombocytopenic purpuraEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2000Chie Yoshimura Abstract: We investigated the levels of various cytokines and soluble factors in ITP patients, in order to determine the influence of these factors on the pathogenesis of ITP. We found increases in IL-2, IL-6, IFN-,, and M-CSF levels in ITP patients compared with those in healthy individuals. On lymphocyte phenotype analysis, we found no clear difference in total T cell population (CD2+ CD19, cells) or cytotoxic T cell frequency (CD8+ CD11b, cells) between these two groups. The frequency of helper/inducer T cells (CD4+ CD8, cells) was decreased in ITP patients. There was a significant increase in activated T cells (CD3+ HLA-DR+ cells) in ITP patients. Furthermore, frequencies of NK cells of potent activity (CD16+ CD56+ cells) were significantly elevated in ITP patients. Seventeen of the 54 ITP patients (31.5%) had elevated levels of sFas, and 11 of the 54 patients (20.4%) of sFasL. In addition, a significant increase of sFasL was observed in sFas-positive ITP patients, and in these patients the sFasL level was correlated with that of sFas (r=0.687, p<0.01). We found significant increases in IL-2 and sIL-2R levels in sFas-positive ITP patients. For other factors examined, however, there were no differences in level between sFas-positive and-negative ITP patients. Percentages of activated T cells (CD3+ and HLA-DR+ cells) and NK cells (CD16+ and CD56+ cells) were significantly higher in sFas-positive ITP patients than in sFas-negative ITP patients. These findings suggests that the pathogenesis of ITP includes alteration of the Fas/FasL pathway. [source] Novel polysialogangliosides of skate brainFEBS JOURNAL, Issue 16 2000Structural determination of tetra, hexasialogangliosides with a NeuAc-GalNAc linkage, penta The gangliosides in the brain of a cartilaginous fish, skate (Bathyraja smirnovi), have been isolated and characterized by means of methylation analysis, antibody binding, enzymatic hydrolysis and MALDI-TOF MS. In addition to gangliosides with known structures (GM2, fucosyl-GM1, GD3, GD2, GT3 and GT2), five polysialogangliosides were isolated and characterized as having the following structures. (1) IV3NeuAc, III6NeuAc, II3NeuAc-Gg4Cer; (2) IV3NeuAc2, III6NeuAc, II3NeuAc-Gg4Cer; (3) IV3NeuAc, III6NeuAc, II3NeuAc2 -Gg4Cer; (4) IV3NeuAc, III6NeuAc, II3NeuAc3 -Gg4Cer; and (5) IV3NeuAc2, III6NeuAc, II3NeuAc3 -Gg4Cer. These structures are ,hybrid-type' which comprise combinations of ,-series and either a, b or c-series structures. Three gangliosides (2), (4) and (5), were novel. The main features of the ganglioside composition of skate brain were an abundance of gangliotriaosyl species, a lack of gangliotetraosyl species (except fucosyl-GM1), and an abundance of hybrid-types. These characteristics closely resemble those in shark brain which we reported previously [Nakamura, K., Tamai, Y. & Kasama, T. (1997) Neurochem. Int.30, 593,604]. Two of the hybrid-type gangliosides (1) and (4), were examined for their neuritogenic activity toward cultured neuronal cells (Neuro-2A), and were found to have more potent activity than nonhybrid-type gangliosides such as GM1. [source] Crystal Structure of an EMAP-II-Like Cytokine Released from a Human tRNA SynthetaseHELVETICA CHIMICA ACTA, Issue 4 2003Xiang-Lei Yang Aminoacyl-tRNA synthetases catalyze the first step of protein synthesis by aminoacylation of tRNAs. Remarkably, biological fragments of two human enzymes , tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase , are active cytokines produced by proteolysis or alternative splicing. One is a C-terminal fragment of TyrRS (C-TyrRS) that has potent activity for chemotaxis of leukocytes and monocytes and for stimulating production of other cytokines. Significantly, the cytokine activity of C-TyrRS is absent in the context of the full-length native protein. Unknown is the mechanism by which domain-release from the dimeric native protein activates the cytokine. Here, the crystal structure of C-TyrRS is presented at 2.2,Å resolution. This structure is similar to that of endothelial monocyte-activating protein II (EMAP-II), with critical residues of a heptapeptide element important for chemotaxis activity exposed on the first strand of a , -barrel of the monomeric unit. In contrast, the same residues of C-TyrRS are buried in an operational model for native TyrRS. Importantly, C-TyrRS is shown here to be monomeric when released from dimeric native TyrRS. Further analysis suggests that the critical residues are exposed when tRNA is bound. Thus, tRNA binding to native TyrRS may be an additional or alternative way to activate cytokine signaling. [source] Antibody response against NY-ESO-1 in CHP-NY-ESO-1 vaccinated patientsINTERNATIONAL JOURNAL OF CANCER, Issue 10 2007Ryohei Kawabata Abstract NY-ESO-1 specific humoral responses are frequently observed in patients with various types of NY-ESO-1 antigen expressing tumors. In a large proportion of NY-ESO-1 antibody-positive patients of NY-ESO-1-specific CD8 T-cells can also be detected suggesting that monitoring of the NY-ESO-1 specific humoral immune response may be a relevant and more practical surrogate for estimating the overall immune response against NY-ESO-1 in clinical vaccine studies. We have immunized 9 cancer patients with full length NY-ESO-1 protein formulated with cholesterol-bearing hydrophobized pullulan (CHP-NY-ESO-1) and investigated the humoral immune responses against NY-ESO-1. Seven patients were NY-ESO-1 antibody-negative and 2 patients were positive prior to vaccination. Vaccination with CHP-NY-ESO-1 resulted in the induction or increase of NY-ESO-1 antibody responses in all 9 patients immunized. Epitope analysis revealed 5 regions in the NY-ESO-1 protein molecule that were recognized by antibodies induced after vaccination. The 5 regions were also recognized by antibodies present in nonvaccinated, NY-ESO-1 antibody-positive cancer patients. A peptide spanning amino acids 91,108 was recognized in 6 out of 9 vaccinated patients and in 8 out of 9 nonvaccinated, sero-positive patients, being the most dominant antigenic epitope in NY-ESO-1 for antibody recognition in cancer patients. In conclusion, we showed that CHP-NY-ESO-1 protein vaccination had a potent activity for inducing humoral immune responses against NY-ESO-1 antigen in cancer patients. The antigenic epitopes recognized by antibodies in the vaccinated patients were similar to those recognized in cancer patients with spontaneous humoral immunity against NY-ESO-1. © 2007 Wiley-Liss, Inc. [source] An effective iodide formulation for killing Bacillus and Geobacillus spores over a wide temperature rangeJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2004N. Kida Abstract Aims:, To develop a sporicidal reagent which shows potent activity against bacterial spores not only at ambient temperatures but also at low temperatures. Methods and Results:, Suspension tests on spores of Bacillus and Geobacillus were conducted with the reagent based on a previously reported agent (N. Kida, Y. Mochizuki and F. Taguchi, Microbiology and Immunology 2003; 47: 279,283). The modified reagent (tentatively designated as the KMT reagent) was composed of 50 mmol l,1 EDTA-2Na, 50 mmol l,1 ferric chloride hexahydrate (FeCl3·6H2O), 50 mmol l,1 potassium iodide (KI) and 50% ethanol in 0·85% NaCl solution at pH 0·3. The KMT reagent showed significant sporicidal activity against three species of Bacillus and Geobacillus spores over a wide range of temperature. The KMT reagent had many practical advantages, i.e. activity was much less affected by organic substances than was sodium hypochlorite, it did not generate any harmful gas and it was stable for a long period at ambient temperatures. The mechanism(s) of sporicidal activity of the KMT reagent was considered to be based on active iodine species penetrating the spores with enhanced permeability of the spore cortex by a synergistic effect of acid, ethanol and generated active oxygen. Conclusions:, The data suggest that the KMT reagent shows potent sporicidal activity over a wide range temperatures and possesses many advantages for practical applications. Significance and Impact of the Study:, The results indicate development of a highly applicable sporicidal reagent against Bacillus and Geobacillus spores. [source] Treatment of invasive candidiasis with echinocandinsMYCOSES, Issue 6 2009Andreas Glöckner Summary Blood stream infections by Candida spp. represent the majority of invasive fungal infections in intensive care patients. The high crude mortality of invasive candidiasis remained essentially unchanged during the last two decades despite new treatment options that became available. The echinocandins, the latest class of antifungals introduced since 2001, exhibit potent activity against clinically relevant fungi including most Candida spp. In several randomised multicentre phase III trials, anidulafungin, caspofungin and micafungin showed convincing efficacy when compared with standard treatment regimens. In all trials, echinocandins were at least non-inferior to standard treatments. Anidulafungin was shown to be superior to fluconazole. Echinocandins have a favourable tolerability profile and exhibit a minimal potential for drug interactions since their pharmacokinetics is independent of renal and , largely , hepatic function. As a result of these properties, echinocandins are appropriate drugs of choice for invasive candidiasis in intensive care where many patients experience organ failure and receive multiple drugs with complex interactions. [source] Antimicrobial and cytotoxic activities of Malaysian endophytesPHYTOTHERAPY RESEARCH, Issue 5 2010Kalavathy Ramasamy Abstract Endophytes, which are receiving increasing attention, have been found to be potential sources of bioactive metabolites following the discovery of paclitaxel producing endophytic fungi. In the present study, a total of 348 endophytes were isolated from different parts of 24 Malaysian medicinal plants. Three selected endophytes (HAB10R12, HAB11R3 and HAB21F25) were investigated for their antimicrobial and cytotoxic activities. For antimicrobial activity, HAB10R12 and HAB11R3 were found to be most active against bacteria and fungi, respectively. Their antimicrobial effects were comparable to, if not better than, a number of current commercial antibacterial and antifungal agents. Both HAB10R12 and HAB21F25 were found to be potential anticancer drug candidates, having potent activity against MCF-7 and HCT116 cell lines and warrant further investigation. Copyright © 2009 John Wiley & Sons, Ltd. [source] Antiviral activity and constituent of Ardisia chinensis benth against coxsackie B3 virusPHYTOTHERAPY RESEARCH, Issue 8 2006Miaoxian Su Abstract Ardisia chinensis Benth is a medicinal plant traditionally used in the area of Yao minority in Southern China. The in vitro antiviral activities of extracts and fractions from Ardisia chinensis were tested by the cytopathic effect (CPE) reduction assay in the present study. As a result, both the aqueous extract and the 95% ethanol extract of Ardisia chinensis showed in vitro antiviral activity against Coxsackie B3 (Cox B3) virus to different extents, and the aqueous extract possessed more potent activity than the ethanol extract. Bioassay-guided fractionation revealed that the antiviral activity of Ardisia chinensis was attributed mainly to its high polar fractions, and finally identified to be a polysaccharide. The Ardisia chinensis polysaccharide (ACP) fractionated from the aqueous extract exhibited a significant antiviral effect against Cox B3 with a 50% inhibitory concentration (IC50) of 3.9 µg/mL and a selective index (SI) over 256. Preliminary characterization indicated that ACP is a neutral polysaccharide in which d -glucose is the major component. The average molecular weights of ACP were determined to be 40037 Da (Mw), 28297 Da (Mn) and 33758 Da (Mp) by gel permeation chromatography. Copyright © 2006 John Wiley & Sons, Ltd. [source] Trypsin inhibitory effect of wedelolactone and demethylwedelolactonePHYTOTHERAPY RESEARCH, Issue 4 2003Samiulla D. Syed Abstract Wedelolactone (WL) and demethylwedelolactone (DWL) isolated from Eclipta alba were tested in the trypsin inhibition bioassay (in vitro). Both compounds showed potent activity. IC50 values of WL and DWL were found to be 2.9 and 3.0 µg/mL respectively. Copyright © 2003 John Wiley & Sons, Ltd. [source] Activity of Zanthoxylum clava-herculis extracts against multi-drug resistant methicillin-resistant Staphylococcus aureus (mdr-MRSA)PHYTOTHERAPY RESEARCH, Issue 3 2003Simon Gibbons Abstract In a continuing search for compounds with antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA) possessing multidrug ef,ux systems, we have demonstrated activity associated with extracts from Southern prickly ash bark, Zanthoxylum clava-herculis. Bioassay-guided isolation of an alkaloid extract led to the characterization of the benzo[c]phenanthridine alkaloid chelerythrine as the major active principle. This compound exhibited potent activity against strains of MRSA, which were highly resistant to clinically useful antibiotics via multidrug ef,ux mechanisms. Copyright © 2003 John Wiley & Sons, Ltd. [source] Comparative activity and stability under salinity conditions of different antimicrobial peptides isolated from aquatic animalsAQUACULTURE RESEARCH, Issue 16 2009Sara Emelie Löfgren Abstract This study reports the in vitro activity of six antimicrobial peptides (AMPs) produced by aquatic animals (most marine invertebrates): tachyplesin (Tach), magainin (Mag), clavanin (Clav), penaeidin (Pen), mytilin (Myt) and antilipopolysaccharide factor (ALF) against marine vibrios, filamentous fungi and yeast. Their stability under salinity conditions and seawater was also examined. The results showed that Mag, Myt and especially Tach and ALF (minimum inhibitory concentration<1.5 ,M) had a potent activity against all tested vibrio species, whereas Clav and Pen were ineffective (up to 50 ,M). With respect to the antifungal activity, each AMP had a different potency according to the fungal species. In general terms, Tach was the most potent peptide, followed by Mag. Interestingly, Tach, Myt and ALF had a significant effect on the filamentous fungus Fusarium solani that could be pathogenic to marine organisms. All AMPs had a tendency to decrease or lose their activity at high salinity (>225 mM NaCl). Tach and Myt were the most stable peptides, maintaining significant activity under seawater salinity (450 mM). Curiously, all peptides lost their effect under seawater conditions. The results suggest that Tach, ALF and Myt are the most promising candidates for potential therapeutic use in farmed-marine species, because all have a significant and broad antimicrobial activity maintained at high salinity. [source] Synthesis and Antibacterial Activity of Novel 4,- O -Carbamoyl Erythromycin-A DerivativesARCHIV DER PHARMAZIE, Issue 8 2010Yunkun Qi Abstract Novel 4,- O -carbamoyl erythromycin-A derivatives were designed, synthesized, and evaluated for their in-vitro antibacterial activities. All of the 4,- O -carbamoyl derivatives showed excellent activity against erythromycin-susceptible Staphylococcus aureus ATCC25923, Streptococcus pyogenes, and Streptococcus pneumoniae ATCC49619. Most of the 4,- O -arylalkylcarbamoyl derivatives displayed potent activity against erythromycin-resistant S. pneumoniae encoded by the mef gene and greatly improved activity against erythromycin-resistant S. pneumoniae encoded by the erm gene or the erm and mef genes. In particular, the 4,- O -arylalkyl derivatives 4c,4e and 4g were found to possess the most potent activity against all the tested erythromycin-susceptible strains, which were comparable to those of erythromycin, clarithromycin, or azithromycin. 4,- O -Arylalkyl derivatives 4e and 4g were the most effective against erythromycin-resistant S. pneumoniae encoded by the mef gene (0.25 and 0.25,µg/mL). 4,- O -Arylalkyl derivatives 4a and 4b exhibited significantly improved activity against erythromycin-resistant S. pneumoniae encoded by the erm gene. In contrast, the 4,- O -alkylcarbamoyl derivatives hardly showed improved activity against all the tested erythromycin-resistant strains. [source] Synthesis and in-vitro Cytotoxicity of Poly-functionalized 4-(2-Arylthiazol-4-yl)-4H -chromenesARCHIV DER PHARMAZIE, Issue 7 2010Majid Mahmoodi Abstract A new series of 4-aryl-4H -chromenes bearing a 2-arylthiazol-4-yl moiety at the 4-position were prepared as potential cytotoxic agents. The in-vitro cytotoxic activity of the synthesized 4-aryl-4H -chromenes was investigated in comparison with etoposide, a well-known anticancer drug, using MTT colorimetric assay. Among them, the 2-(2-chlorophenyl)thiazol-4-yl analog 4b showed the most potent activity against nasopharyngeal epidermoid carcinoma KB, medulloblastoma DAOY, and astrocytoma 1321N1, and compound 4d bearing a 2-(4-chlorophenyl)thiazol-4-yl moiety at the 4-position of the chromene ring exhibited the best inhibitory activity against breast cancer cells MCF-7, lung cancer cells A549, and colon adenocarcinoma cells SW480 with IC50 values less than 5 ,M. The ability of compound 4b to induce apoptosis was confirmed in a nuclear morphological assay by DAPI staining in the KB and MCF-7 cells. [source] 6-Substituted Indolo[1,2- c]quinazolines as New Antimicrobial AgentsARCHIV DER PHARMAZIE, Issue 9 2009Rondla Rohini Abstract A series of 2- o -arylidineaminophenylindoles and their cyclic derivatives (indolo[1,2- c]quinazolines) were synthesized. The reactions occurred under relatively mild conditions and afforded the desired product in good yields. Molecular structures of the synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, MS spectra, and elemental analyses. Furthermore, all the final products were screened for in-vitro antibacterial activity against three Gram-positive and three Gram-negative bacteria and also tested for their inhibitory action against three strains of fungi. Compound IIc showed potent activity against all the bacterial (except S. typhimurium) and fungal strains. Especially, compounds IIi and IIj which have isoquinolyl and pyridyl substituents displayed potent antibacterial as well as antifungal activities compared to those of the respective standard drugs Ampicillin and Ketoconazole. [source] Synthesis and Anti-Inflammatory Activity of Novel (4-Hydroxyphenyl)(2,4-dimethoxyphenyl) Methanone DerivativesARCHIV DER PHARMAZIE, Issue 8 2009Kambappa Vinaya Abstract In the scope of the research program aiming to perform the synthesis and pharmacological evaluation of novel possible anti-inflammatory compounds, in this manuscript, we report the synthesis of novel carboxamide 9a - d and thioamide 10a - d derivatives from the benzophenone and piperidine nucleus. Variation in the functional group at the N -terminal of piperidine led to two sets of compounds, bearing the carboxamide and thioamide, respectively. The characterization of this new class of compounds was performed with 1H-NMR, LC-MS, IR, and elemental analysis. The newly synthesized compounds were screened for their anti-inflammatory activity by carrageenan-induced foot pad oedema assay and were compared with a standard drug. All the compounds exhibited anti-inflammatory activity at the dose of 30 mg/kg p.o. with varying degree from 52 to 67% inhibition of oedema. The compounds 9d and 10d with dichloro and fluoro substitution showed more potent activity at 30 mg/kg p.o. than the standard drug. [source] Design, Synthesis, and Biological Evaluation of Prenylated Chalcones as Vasorelaxant AgentsARCHIV DER PHARMAZIE, Issue 7 2009Xiaowu Dong Abstract Five prenylated chalcones and one allylated chalcone were prepared according to the analysis based on support vector machine (SVM) classification model. Most of the synthesized chalcones showed potent vasorelaxant activities through evaluation in aortic rings with the endothelium pre-contracted by phenylephrine (PE), indicating that the experimental activities were in good agreement with the theoretical ones. Structure-activity relationship of these compounds showed that the substituent pattern and number of hydroxyl groups were crucial for their vasorelaxant activities and that the replacement of prenyl group with allyl group retained the potent activity. [source] Structure of the ligand-binding domain of rat VDR in complex with the nonsecosteroidal vitamin D3 analogue YR301ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 11 2008Shinji Kakuda Vitamin D receptor (VDR) is a ligand-inducible hormone receptor that mediates 1,,25(OH)2D3 action, regulating calcium and phosphate metabolism, induces potent cell differentiation activity and has immunosuppressive effects. Analogues of 1,,25(OH)2D3 have been used clinically for some years. However, the risk of potential side effects limits the use of these substances. LG190178 is a novel nonsecosteroidal ligand for VDR. (2S)-3-[4-(3-{4-[(2R)-2-hydroxy-3,3-dimethylbutoxy]-3-methylphenyl}pentan-3-yl)-2-methylphenoxy] propane-1,2-diol (YR301) is the only one of the four evaluated stereoisomers of LG190178 to have strong activity. To understand the strong activity of YR301, the crystal structure of YR301 complexed with the rat VDR ligand-binding domain (VDR LBD) was solved at 2.0,Å resolution and compared with the structure of the VDR LBD,1,,25(OH)2D3 complex. YR301 and 1,,25(OH)2D3 share the same position and the diethylmethyl group occupies a similar space to the C and D rings of 1,,25(OH)2D3. YR301 has two characteristic hydroxyl groups which contribute to its potent activity. The first is 2,-OH, which forms hydrogen bonds to the NE2 atoms of both His301 and His393. The other is 2-OH, which interacts with Ser233,OG and Arg270,NH1. These two hydroxyl groups of YR301 correspond exactly to 25-OH and 1-OH, respectively, of 1,,25(OH)2D3. The terminal hydroxyl group (3-OH) of YR301 is directly hydrogen bonded to Arg270 and also interacts indirectly with Tyr232,OH and the backbone NH of Asp144 via water molecules. Additional derivatization of the terminal hydroxyl group using the positions of the water molecules might be useful for the design of more potent compounds. [source] Triptolide abrogates oncogene FIP1L1-PDGFR, addiction and induces apoptosis in hypereosinophilic syndromeCANCER SCIENCE, Issue 11 2009Yanli Jin The pathogenesis of hypereosinophilic syndrome (HES) in some patients is highly dependent on FIP1-Like-1 (FIP1L1),platelet-derived growth factor receptor alpha (PDGFR,), which can generate sustained activation signaling to maintain a cell malignant phenotype. HES usually shows good response to the tyrosine kinase inhibitor imatinib, but mutations in FIP1L1-PDGFR, (e.g. T674I) can confer acquired resistance to imatinib. An alternative therapeutic strategy other than with tyrosine kinase inhibitors is needed to overcome acquired drug resistance. We hypothesized that switching off the crucial chimeric oncoprotein FIP1L1-PDGFR, on which HES cells depend, should have deleterious effects on the cancer cells. We used low concentrations of triptolide, a transcription inhibitor, to shut down the expression of FIP1L1-PDGFR,. EOL-1 cells and BaF3 cells expressing wild-type or T674I FIP1L1-PDGFR, were treated with triptolide, and signaling pathways, cell cycling, and apoptosis were analyzed by RT-PCR, immunoblotting, and flow cytometry, respectively. The results revealed that at nanomolar concentrations triptolide decreased the levels of mRNA and protein of FIP1L1-PDGFR, and the growth of the neoplastic cells, regardless of the mutational status of PDGFR,. Triptolide also downregulated the signaling molecules Stat3, Akt, and Erk1/2, which are downstream from PDGFR,, and induced G1 cell-cycle arrest. Triptolide time- and dose-dependently induced apoptosis by decreasing the anti-apoptotic proteins Mcl-1 and Bcl-XL,triggering the intrinsic apoptotic pathway. In conclusion, triptolide has potent activity against malignant cells in HES bearing FIP1L1-PDGFR,, regardless of its mutational status that confer acquired resistance to imatinib. Our results suggest that triptolide may be a promising agent in the treatment of HES. (Cancer Sci 2009; 00: 000,000) [source] Strong immunostimulation in murine immune cells by Lactobacillus rhamnosus GG DNA containing novel oligodeoxynucleotide patternCELLULAR MICROBIOLOGY, Issue 3 2005Iliyan D. Iliev Summary Whole cells, cell wall components and some soluble factors from Lactobacillus rhamnosus GG (LGG) are known to invoke immune responses as they interact with animal and human immune cells. In the present study, we found that chromosomal DNA from LGG is a potent inducer of splenic B cell proliferation, CD86/CD69 expression and cytokine production in mice. In the genomic DNA of LGG we discovered TTTCGTTT oligodeoxynucleotide (ODN) ID35, which has a potent activity in a number of immunostimulatory assays. Phosphorothioate backbone is not required for the activity of ID35. The ODN ID35 showed levels of activity comparable with those induced by the murine prototype ODN 1826 in B cell proliferation, CD86/CD69 expression, interleukin (IL)-6, IL-12, IL-18, interferon gamma (IFN-,) and tumour necrosis factor alpha (TNF-,) mRNA expression and IFN-,/IL-12p70 protein production assays. Additionally, ID35 appeared to be equally active in both murine and human immune cells. These stimulatory effects are due to TTTCGTTT motif located in the 5, end of ID35. In this study we demonstrate for a first time that, DNA from LGG is a factor of immunobiotic activity. Furthermore, ODN ID35 is the first ODN, with such a strong immunostimulatory activity to be found in immunobiotic bacterial DNA. [source] | ||||||||||||||||