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At least 1,009 records · Page 56Linked to original sources
PubMed2003

Polyphenolic antioxidants inhibit peptide presentation by antigen-presenting cells.

Antigen-presenting cells (APC) provide two essential signals, e.g., antigenic peptides as well as costimulatory molecules for T-cell activation. Small molecules of smoke tobacco extracts (SM-STE) inhibited antigen presentation of A20 to OVAp-specific T-cell hybridomas. Pretreatment of A20 but not T hybridomas abrogates the APC function. Viability of APC and levels of MHCII, CD40 and B7 of APC were not affected by this treatment. The active principle, inhibiting APC was reproduced with pure tobacco polyphenols, quercetin and its glycoside, rutin. Antioxidant activity of rutin is relevant since rutin downregulated levels of reactive oxygen species (ROS) in phorbol ester-stimulated A20; moreover, another antioxidant, N-acetyl cysteine (NAC) also inhibited antigen presentation, albeit at a higher concentration. Other types of APC, such as bone marrow-derived mast cells (BMMC), MHCII-transfected fibroblast, and splenocytes are affected by tobacco polyphenols. We propose that polyphenols may affect redox-sensitive signal transduction pathway since APC function of PD 98059, MEK inhibitor-pretreated A20 were similarly abrogated. Taken together, we propose that maintaining appropriate intracellular redox of APC is crucial for its antigen-presenting function.

Acetylcysteine↗
PubMed2004

In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds.

Effective antiviral agents are urgently needed to combat the possible return of severe acute respiratory syndrome (SARS). Commercial antiviral agents and pure chemical compounds extracted from traditional Chinese medicinal herbs were screened against 10 clinical isolates of SARS coronavirus by neutralisation tests with confirmation by plaque reduction assays. Interferon-beta-1a, leukocytic interferon-alpha, ribavirin, lopinavir, rimantadine, baicalin and glycyrrhizin showed antiviral activity. The two interferons were only active if the cell lines were pre-incubated with the drugs 16 h before viral inoculation. Results were confirmed by plaque reduction assays. Antiviral activity varied with the use of different cell lines. Checkerboard assays for synergy were performed showing combinations of interferon beta-1a or leukocytic interferon-alpha with ribavirin are synergistic. Since the clinical and toxicity profiles of these agents are well known, they should be considered either singly or in combination for prophylaxis or treatment of SARS in randomised placebo controlled trials in future epidemics.

Adult↗
PubMed2003

Status of free radicals in Indian monsooned coffee beans gamma-irradiated for disinfestation.

Free radicals in two cultivars of Indian monsooned coffee beans, gamma-irradiated for hygienic and quarantine purposes, were examined by entrapping the small amount of samples in potassium chloride powder in ESR quartz tubes. In contrast to a prominent free radical signal at g = 2.002, observed in spermoderm (silver skin) and cotyledon (whole seed without skin) parts of normal coffee beans, the same was not discernible in monsooned coffee bean parts of both cultivars. The ESR signal was found to be more prominent in the spermoderm than in the whole seed portion of the normal coffee beans. Common practices of roasting and powdering were found to generate quantitatively more free radicals in coffee beans than gamma-irradiation alone. Phenols, contributing maximally to observed free radical signals in coffee beans, were significantly different in normal and monsooned coffee beans. These observations on insignificant free radical population in irradiated monsooned coffee beans may be attributed to their inherent possession of high water activity, favoring decay of free radicals produced. Textural studies with monsooned coffee beans, before and after mild heat treatments, supported these findings.

Chlorogenic Acid↗
PubMed2007

MT1-MMP down-regulates the glucose 6-phosphate transporter expression in marrow stromal cells: a molecular link between pro-MMP-2 activation, chemotaxis, and cell survival.

Bone marrow-derived stromal cells (BMSC) are avidly recruited by experimental vascularizing tumors, which implies that they must respond to tumor-derived growth factor cues. In fact, BMSC chemotaxis and cell survival are regulated, in part, by the membrane type-1 matrix metalloproteinase (MT1-MMP), an MMP also involved in pro-MMP-2 activation and in degradation of the extracellular matrix (ECM). Given that impaired chemotaxis was recently observed in bone marrow cells isolated from a glucose 6-phosphate transporter-deficient (G6PT-/-) mouse model, we sought to investigate the potential MT1-MMP/G6PT signaling axis in BMSC. We show that MT1-MMP-mediated activation of pro-MMP-2 by concanavalin A (ConA) correlated with an increase in the sub-G1 cell cycle phase as well as with cell necrosis, indicative of a decrease in BMSC survival. BMSC isolated from Egr-1-/- mouse or MT1-MMP gene silencing in BMSC with small interfering RNA (siMT1-MMP) antagonized both the ConA-mediated activation of pro-MMP-2 and the induction of cell necrosis. Overexpression of recombinant full-length MT1-MMP triggered necrosis and this was signaled through the cytoplasmic domain of MT1-MMP. ConA inhibited both the gene and protein expression of G6PT, while overexpression of recombinant G6PT inhibited MT1-MMP-mediated pro-MMP-2 activation but could not rescue BMSC from ConA-induced cell necrosis. Cell chemotaxis in response to the tumorigenic growth factor sphingosine 1-phosphate was significantly abrogated in siMT1-MMP BMSC and in chlorogenic acid-treated BMSC. Altogether, we provide evidence for an MT1-MMP/G6PT signaling axis that regulates BMSC survival, ECM degradation, and mobilization. This may lead to optimized clinical applications that use BMSC as a platform for the systemic delivery of therapeutic or anti-cancer recombinant proteins in vivo.

Animals↗
PubMed2004

Polyphenolic antioxidants enhance IgE production.

Epidemiological data showed that total IgE and IL-4 levels in cigarette smokers were elevated, comparable to those in the asthmatics. The etiological agent(s) elevating IgE production are not clear. We evaluate whether tobacco polyphenols potentiate IgE production in a rodent model. Mice were fed with rutin or CGA in drinking water during antigen sensitization, followed by antigenic challenge i.p. in alum. CGA and rutin were also delivered in a bolus intraperitoneally or intranasally along with antigens during immunization. Antigen-specific IgE and IgG responses were measured. Enhancement of total IgE responses via i.p. and drinking routes can be achieved at concentrations as low as 0.1% CGA. Furthermore, IgG1 responses but not IgG2a and IgG2b were augmented, indicating a Th2 type of response by CGA. Moreover, both antigen-specific and serum IgE production can be achieved when CGA and antigenic challenges were delivered intranasally in the absence of alum. In contrast, nicotine does not enhance antigen-specific IgE production, and only marginally affects serum IgE levels. The more polarized Th2 development in CGA-treated mice may account for enhancement of both antigen-specific and total IgE responses. High levels of IL-4 but not IFN-gamma or IL-12, were observed in antigen-challenged mesenteric lymph nodes (MLN) cultures from CGA-treated mice. In contrast, significant levels of IL-4, IL-12, and IFN-gamma were observed in antigen-challenged cultures from nicotine-treated mice. This study shows that tobacco polyphenols, CGA and rutin potentiated IgE production in vivo. Polyphenolic antioxidants enhance Th2 development. We propose that IgE production and T cell dichotomy may be critically influenced by the redox microenvironment. Enhanced Th2 development and IgE production henceforth may counteract more severe Th1-mediated tissue damage triggered by environmental oxidative stress.

Animals↗
PubMed2003

Genes for chlorogenate and hydroxycinnamate catabolism (hca) are linked to functionally related genes in the dca-pca-qui-pob-hca chromosomal cluster of Acinetobacter sp. strain ADP1.

Hydroxycinnamates are ubiquitous in the environment because of their contributions to the structure and defense mechanisms of plants. Additional plant products, many of which are formed in response to stress, support the growth of Acinetobacter sp. strain ADP1 through pathways encoded by genes in the dca-pca-qui-pob chromosomal cluster. In an appropriate genetic background, it was possible to select for an Acinetobacter strain that had lost the ability to grow with caffeate, a commonly occurring hydroxycinnamate. The newly identified mutation was shown to be a deletion in a gene designated hcaC and encoding a ligase required for conversion of commonly occurring hydroxycinnamates (caffeate, ferulate, coumarate, and 3,4-dihydroxyphenylpropionate) to thioesters. Linkage analysis showed that hcaC is linked to pobA. Downstream from hcaC and transcribed in the direction opposite the direction of pobA transcription are open reading frames designated hcaDEFG. Functions of these genes were inferred from sequence comparisons and from the properties of knockout mutants. HcaD corresponded to an acyl coenzyme A (acyl-CoA) dehydrogenase required for conversion of 3,4-dihydroxyphenylpropionyl-CoA to caffeoyl-CoA. HcaE appears to encode a member of a family of outer membrane proteins known as porins. Knockout mutations in hcaF confer no discernible phenotype. Knockout mutations in hcaG indicate that this gene encodes a membrane-associated esterase that hydrolyzes chlorogenate to quinate, which is metabolized in the periplasm, and caffeate, which is metabolized by intracellular enzymes. The chromosomal location of hcaG, between hcaC (required for growth with caffeate) and quiA (required for growth with quinate), provided the essential clue that led to the genetic test of HcaG as the esterase that produces caffeate and quinate from chlorogenate. Thus, in this study, organization within what is now established as the dca-pca-qui-pob-hca chromosomal cluster provided essential information about the function of genes in the environment.

Acinetobacter↗