PubMed · 7395491
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
J Jákó. Problems caused by immunodeficiencies.. https://doi.org/10.3109/00016488009127126
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
A series of naphthalene derivatives with a variety of substituents at the 2-position was prepared in order to evaluate their suppressive effect on immunoglobulin E (IgE) antibody production by human peripheral blood mononuclear cells provoked with anti-CD40 antibody (alpha-CD40), interleukin-4 (IL-4), and interleukin-10 (IL-10). Compounds having a 1,4-phenylene spacer moiety tethered between the 2-naphthyl nucleus and anthranilic acid suppressed IgE antibody production in vitro in preference to that of IgG antibody without affecting cell viability. Deletion of the anthranilic acid moiety diminished the inhibitory activities. Changing the 2-naphthyl to a 1-naphthyl or phenyl nucleus led to no change in the potency, indicating that the aromatic group at this position is indispensable for the inhibitory activities. On the other hand, changing the 1,4-phenylene spacer to a 1,3-phenylene one resulted in reduced potency. Similarly, inhibitory activities were lost when the CO2H moiety at the 2-position was moved to the 3- or 4-position on the terminal benzene. These observations suggest that the conformation around the anthranilic acid moiety affects the inhibitory activities toward IgE biosynthesis. 2-(4-(2-Naphthyloxy)benzamido)benzoic acid (29) seemed to be a more potent inhibitor of IgE production than of IgG production. Insertion of a methylene between the inter-phenylene and the amide moiety resulted in 2-((4-(2-naphthyloxy)phenyl)acetamido)benzoic acid (31), which provided a stronger inhibition of both IgE and IgG production, although the selectivity toward IgE was lower than that of 29. Introduction of a benzyl group at the 6-position on the naphthalene ring considerably increased the inhibitory activity toward IgE production with an IC50 of 8.3 nM (36). The potency of 31 and 36 was retained when hydrocortisone or lipopolysaccharide was used instead of alpha-CD40 and IL-10 as costimulatory factors with IL-4, implying that these compounds may interfere with signal transduction between IL-4/IL-4 receptor cognition and genetic transcription that induce class-switching of immunoglobulin in B cells. These novel naphthalene derivatives are thus excellent candidates for further investigation with a view toward a therapeutic remedy against IgE-mediated allergic diseases.
A polyclonal antibody, R2, was raised against a fusion protein consisting of a portion of plant hsp90 fused to the trpE protein of Escherichia coli. This antibody was found to be specific towards plant hsp90, showing little or no cross-reactivity with mouse and human hsp90 proteins. The R2 antibody identified an 83 kDa protein as the hsp90 homologue in cytosolic extracts of several dicot and monocot plants. Two-dimensional gel electrophoresis indicated that at least two different isoforms of hsp90 are expressed in Brassica napus seedlings. An examination of the native state of hsp90 by non-denaturing gel electrophoresis showed that this protein exists as a monomer, dimer and as a high-molecular-mass complex of ca. 680 kDa in cell extracts of spinach cotyledons and leaves, B. napus seedlings and wheat germ. Native gel analysis and cross-linking studies of purified hsp90 showed that plant hsp90 exists predominantly as a monomer. When 35S-labelled B. napus cytosolic extracts were immunoprecipitated with the R2 antiserum, hsp90 and two additional proteins with approximate molecular masses of 49 and 45 kDa were detected in the immunoprecipitates. These results are consistent with the idea that hsp90:protein heterocomplexes exist in plant cells.
Understanding the extent to which genetic factors influence the immune response is important in the development of subunit vaccines. Associations with HLA gene polymorphisms appear insufficient to explain the range of variation in immune responses to vaccines and to infections by major pathogens. In this study of Gambian twins we report that regulation of the immune response to a variety of antigens from Plasmodium falciparum and Mycobacterium tuberculosis is controlled by factors which are encoded by genes that lie both within and outside the major histocompatibility complex (MHC). We define the relative contribution of these genes, which varies for different antigens. The cumulative genetic contribution of non-MHC genes to the total phenotypic variance exceeds that of the MHC-encoded genes.