Various allergic responses are thought to result from the unbalanced development of T(H)1 and T(H... more Various allergic responses are thought to result from the unbalanced development of T(H)1 and T(H)2 pathways and, subsequently, the overproduction of IgE. Therefore the modulation of T(H)1 and T(H)2 responses is a rational strategy for the treatment of allergic diseases. The present study was performed to investigate the immune-modulating activities of PG102 preparations from Actinidia arguta in ovalbumin-sensitized murine models. Two preparations from A arguta, PG102T and PG102E, were chosen for animal experimentation on the basis of their ability to regulate the production of IgE in U266B1 cells. The changes in splenic levels of cytokines and plasma levels of immunoglobulin isotypes were examined. The effects of PG102 on subcellular composition (CD4(+)IL-4(+) or CD19(+)IgE(+) cells), IgE production in B cells, and selective transcription factors were analyzed. Oral administration of PG102T and PG102E significantly decreased the level of selective T(H)2 cytokines, whereas it increased the level of T(H)1 cytokines. The differential effects of PG102T and PG102E on T(H)1 and T(H)2 cytokines were accompanied by a decrease in the plasma levels of IgE and IgG1 and by an increase in the plasma level of IgG2a. The percentages of both IL-4-producing T cells and IgE-producing B cells were decreased. The concentration of IgE produced within B cells also appeared to be reduced. Finally, PG102T and PG102E downregulated the level of GATA-binding protein 3, while inducing that of T-box transcription factor and nuclear factor of activated T cells c2. PG102T and PG102E have great potential as orally active immune modulators for the therapy of various allergic diseases.
Journal of The American Society for Mass Spectrometry, 2006
We report the electron capture dissociation (ECD) mass spectrometry of the third generation polya... more We report the electron capture dissociation (ECD) mass spectrometry of the third generation polyamidoamine (PAMAM) dendrimer that contains amide functionalities. The dendrimer was chosen because it offers a unique opportunity to understand the ECD behavior of the amide functionality in a framework other than peptides/proteins. In this study, PAMAM ECD was found to exhibit a fragmentation pattern strikingly different from that of ordinary peptide/protein ECD. Specifically, ECD of multiply protonated PAMAM ions gave rise to significant b •,y cleavages as well as S,E dissociations but, unexpectedly, only minor c,z • fragmentations are observed. In an effort to account for the unexpectedly different fragmentation pattern, a comparative ECD experiment on the poly(propylene imine) dendrimer in which the amide bond moiety is not available and density functional theory calculations (B3LYP/6-311+G(d)) investigations on the model system of a charge-solvated single-repeat unit were carried out. On the basis of these results, we discuss here possible implications of intramolecular charge-solvation, energy barriers in dissociation reactions, and macromolecular properties of the dendritic molecule for understanding the reaction pathway of PAMAM ECD.
Various allergic responses are thought to result from the unbalanced development of T(H)1 and T(H... more Various allergic responses are thought to result from the unbalanced development of T(H)1 and T(H)2 pathways and, subsequently, the overproduction of IgE. Therefore the modulation of T(H)1 and T(H)2 responses is a rational strategy for the treatment of allergic diseases. The present study was performed to investigate the immune-modulating activities of PG102 preparations from Actinidia arguta in ovalbumin-sensitized murine models. Two preparations from A arguta, PG102T and PG102E, were chosen for animal experimentation on the basis of their ability to regulate the production of IgE in U266B1 cells. The changes in splenic levels of cytokines and plasma levels of immunoglobulin isotypes were examined. The effects of PG102 on subcellular composition (CD4(+)IL-4(+) or CD19(+)IgE(+) cells), IgE production in B cells, and selective transcription factors were analyzed. Oral administration of PG102T and PG102E significantly decreased the level of selective T(H)2 cytokines, whereas it increased the level of T(H)1 cytokines. The differential effects of PG102T and PG102E on T(H)1 and T(H)2 cytokines were accompanied by a decrease in the plasma levels of IgE and IgG1 and by an increase in the plasma level of IgG2a. The percentages of both IL-4-producing T cells and IgE-producing B cells were decreased. The concentration of IgE produced within B cells also appeared to be reduced. Finally, PG102T and PG102E downregulated the level of GATA-binding protein 3, while inducing that of T-box transcription factor and nuclear factor of activated T cells c2. PG102T and PG102E have great potential as orally active immune modulators for the therapy of various allergic diseases.
Journal of The American Society for Mass Spectrometry, 2006
We report the electron capture dissociation (ECD) mass spectrometry of the third generation polya... more We report the electron capture dissociation (ECD) mass spectrometry of the third generation polyamidoamine (PAMAM) dendrimer that contains amide functionalities. The dendrimer was chosen because it offers a unique opportunity to understand the ECD behavior of the amide functionality in a framework other than peptides/proteins. In this study, PAMAM ECD was found to exhibit a fragmentation pattern strikingly different from that of ordinary peptide/protein ECD. Specifically, ECD of multiply protonated PAMAM ions gave rise to significant b •,y cleavages as well as S,E dissociations but, unexpectedly, only minor c,z • fragmentations are observed. In an effort to account for the unexpectedly different fragmentation pattern, a comparative ECD experiment on the poly(propylene imine) dendrimer in which the amide bond moiety is not available and density functional theory calculations (B3LYP/6-311+G(d)) investigations on the model system of a charge-solvated single-repeat unit were carried out. On the basis of these results, we discuss here possible implications of intramolecular charge-solvation, energy barriers in dissociation reactions, and macromolecular properties of the dendritic molecule for understanding the reaction pathway of PAMAM ECD.
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