Glucocorticoid hormones in immunomodulating effect of defensins

Defensins are a family of antimicrobial cationic peptides localized mainly in neutrophile granulocytes. The defensins are known to display corticostatic activity by means of suppression of stress- and ACTH-induced rise in corticosterone level in the blood. The present study examines influence of defensin fractions with different corticostatic activity on suppressor functions of T-lymphocytes. It was shown that corticostatic effects of defensins are revealed under an increased level of glucocorticoids in the blood after hydrocortisone application. Defensins were found to limit the inhibitory action of glucocorticoids on the suppressor functions of T-lymphocytes. After adrenalectomy this phenomenon was not observed.     

Ganglioside GM3 derivatives and their immunomodulating effect

The derivatives of ganglioside GM3-NeuLacCer. NeuLacSph and NeuAcLacSphAc-were obtained and their immunomodulating properties studied. These substances are shown to inhibit lymphocyte blast-transformation independently of their ceramide structure. On the contrary, the stimulation by the above GM3-derivatives of Con A-induced T-suppressor activity depends significantly on the structure of their ceramide moiety.     

Characteristics of immunomodulating effect of histamine in inbred strain mice]

The activity of 5'-nucleotidase of peritoneal exudate in subcutaneous injection of histamine in a dose of 1.0-100 microliters was studied in mice of different lines (CBA, C57, B1/6, Balb/c, NFS/n, NFR/n). There were interline differences in the influence of histamine on this metabolic index.     

Properties of retinoids

Retinoids are unstable compounds being readily oxidized and/or isomerized to altered compounds, especially in the presence of oxidants including air, light, and excessive heat. They are labile toward strong acids and solvents that have dissolved oxygen or peroxides. In this review, procedures for handling and storage of retinoids and biological samples containing them have been described. The physical and chemical properties of retinoids have been reported. Simplified procedures for derivatizations and purification, and methods for quantitation of retinoids have been presented.     

Antiinflammatory and immunomodulating properties of fungal metabolites

We discuss current information on the ability of extracts and isolated metabolites from mushrooms to modulate immune responses. This can result in a more enhanced innate and acquired disease resistance. The major immunomodulating effects of these active substances derived from mushrooms include mitogenicity and activation of immune effector cells, such as lymphocytes, macrophages, and natural killer cells, resulting in the production of cytokines, including interleukins (ILs), tumor necrosis factor alpha (TNF)-alpha, and interferon gamma (INF)-gamma. In particular, the ability of selective mushroom extracts to modulate the differentiation capacity of CD4(+) T cells to mature into T(H)1 and/or T(H)2 subsets will be discussed. As a consequence these extracts will have profound effects in particular diseases, like chronic autoimmune T(H)1-mediated or allergic T(H)2-mediated diseases. Immunosuppressive effects by mushroom components have also been observed. The therapeutic effects of mushrooms, such as anticancer activity, suppression of autoimmune diseases, and allergy have been associated with their immunomodulating effects. However, further studies are needed to determine the molecular mechanisms of the immunomodulating effects of mushrooms metabolites both individually and in complex mixtures, for example, extracts.     

Separation, structure characterization, conformation and immunomodulating effect of a hyperbranched heteroglycan from Radix Astragali

A water soluble polysaccharide (RAP) was isolated and purified from Radix Astragali and its structure was elucidated by monosaccharide composition, partial acid hydrolysis and methylation analysis, and further supported by FT-IR, GC-MS and ¹H and ¹³C NMR spectra, SEM and AFM microscopy. Its average molecular weight was 1334 kDa. It was composed of Rha, Ara, Glc, Gal and GalA in a molar ratio of 0.03:1.00:0.27:0.36:0.30. The backbone consisted of 1,2,4-linked Rhap, α-1,4-linked Glcp, α-1,4-linked GalAp6Me, β-1,3,6-linked Galp, with branched at O-4 of the 1,2,4-linked Rhap and O-3 or O-4 of β-1,3,6-linked Galp. The side chains mainly consisted of α-T-Araf and α-1,5-linked Araf with O-3 as branching points, having trace Glc and Gal. The terminal residues were T-linked Araf, T-linked Glcp and T-linked Galp. Morphology analysis showed that RAP took random coil feature. RAP exhibited significant immunomodulating effects by stimulating the proliferation of human peripheral blood mononuclear cells and enhancing its interleukin production.     

Kinetics of human alcohol dehydrogenase with ring-oxidized retinoids: effect of Tween 80

Human alcohol dehydrogenases (ADH1 and ADH4) actively use retinoids oxidized at the cyclohexenyl ring (4-oxo-, 4-hydroxy-, and 3,4-didehydro-retinoids), which are functional compounds in several cells and tissues (i.e., in human skin). Remarkably, activities with 4-oxo-retinal and 4-hydroxy-retinol (kcat = 2050 min(-1) for ADH4) are the highest among retinoids, similar to those of the best aliphatic alcohols. Thus, ADH1 and ADH4 provide a metabolic pathway for the synthesis of the corresponding retinoic acids. Tween 80, a widely used detergent in the retinoid activity assay, behaves as a competitive inhibitor. The Km values for all-trans-retinol (2-3 microM), estimated in the absence of detergent, are 10-fold lower than those obtained at the usual 0.02% Tween 80. This suggests a contribution of ADH to retinoid metabolism more relevant than previously expected. However, Tween 80 stabilizes retinoids in water solution and provides a reliable and reproducible assay, suitable for comparing different ADHs and different retinoid substrates.     

Infrared spectroscopy of retinoids

The Fourier transform infrared spectra of 15 purified retinoids were compared. Retinoids with conjugated C = O groups revealed the presence of a band between 1730 and 1630 cm-1 X A characteristic of retinoids is the presence of a band between 1650 and 1620 cm-1 due to C = C stretching where three to four conjugated C = O and C = C bonds were present or between 1610 and 1555 cm-1 where more conjugated unsaturations were present. The presence of cis double bonds was confirmed by a band at 1380 cm-1 while unsubstituted trans double bonds gave absorbances at 990 to 955 cm-1. Epoxy rings, which are present in some retinoids, resulted in bands at 1250, 880, and 790 cm-1 while a furan structure was confirmed by bands at 1175, 1083, and 1065 cm-1.     

The immunomodulating properties of translam]

Effect of translam--beta-1,3;1,6-D-glucan on some of naturally occurring host protective mechanisms was investigated. It was shown that translam has potent biological activity: it has preventive effect on experimental bacterial infections, it stimulates absorbtion and digestion activity of mononuclear phagocytes, it effects on humoral and cell immunity. Translam had mitogenic activity.     

Antitussive and immunomodulating activities of instant coffee arabinogalactan-protein

A low molecular mass arabinogalactan-protein (AGP) composed of galactose and arabinose with a low protein content, isolated from the instant coffee powder of Coffea arabica beans, has been tested on antitussive (in vivo) and immunomodulating (ex vivo) activities. The results of antitussive tests revealed a significant dose dependant cough-suppressive effect of coffee AGP. It was observed 30 or 60 min after AGP administration and its efficacy lasted during the entire experiment course. Immunological tests showed that AGP affected some mediators of immunocompetent cells of immune system as TNF-α, IFN-γ and IL-2 cytokines. It seems that coffee AGP is a good inductor of both pro-inflammatory cytokines TNF-α and IFN-γ, however, less potent in TNF-α induction in comparison with that of β-d-glucan. Evident induction of TNF-α, IL-2 and IFN-γ cytokines, pro-TH1 polarization supports our conclusion about bio-immunological efficacy of AGP with an emphasis on the cellular immunity.     

The effect of retinoids, carotenoids and phenolics on chromosomal instability of bovine papillomavirus DNA-carrying cells

Antioxidants were found to protect against the genotoxic effects of chemical and physical mutagenic and clastogenic agents. This study focused on the capacity of antioxidants to reduce an intrinsic and persistent chromosome instability. As a model system, strains of C127 cells, which were transformed by bovine papillomavirus (BPV) DNA and which carry BPV DNA varying from 20 to 160 copies, were used. Transformed cells of 10 different strains showed a persistently high incidence of mitotic irregularities detectable at anaphase and telophase (27.3-58.9%), an elevated frequency of cells with micronuclei (6.6-34.7%), and a broad spectrum of nuclear sizes, as measured by image analysis. A 3-day exposure to retinoic acid, retinol, beta-carotene, canthaxanthin, ascorbic acid and ellagic acid greatly reduced the degree of chromosome instability, whereas catechin, eugenol and pyrogallol showed a smaller inhibitory effect, and curcumin had no detectable effect on the frequency of mitotic irregularities. After withdrawal of retinoic acid treatment, the high levels of chromosome instability reappeared. The possibility that the protective effect of the retinoids and carotenoids examined in the model system points to their beneficial administration to human cells with an intrinsic or acquired chromosome instability is discussed.     

The immunomodulating properties of staphylotoxin]

The action of native staphylotoxin has been tested on T lymphocytes obtained from 21 healthy human donors. As revealed in this investigation, toxic action affects Fc-receptors to IgG, IgM and IgA. The dose-dependent effect of the preparation suggests its direct contacts with Fc-receptors of lymphocytic membranes. High doses of the toxin suppress the expression of Fc-receptors 6- to 12-fold, low doses of the toxin are capable of stimulating the expression of Fc gamma-receptors.     

Synergistic effect of vitamin D derivatives and retinoids on C2C12 skeletal muscle cells

The response of C2C12 myoblasts to 1 nM 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], two vitamin D analogues (KH 1060 and EB 1089, which are 20-epi-22-oxa and 22,24-diene-analogues, respectively), 100 nM retinoids (9-cis retinoic acid, all-trans retinoic acid) and to combination treatments, after 72 h incubation, was studied. The incubation with 1,25(OH)2D3 was ineffective on either cell proliferation or [3H]thymidine incorporation (expressed as DPM per cell) or protein content per cell. On the contrary, all the other treatments inhibited cell proliferation, this inhibition being synergistic when the vitamin D derivatives were combined with 9-cis or all-trans retinoic acid, and increased [3H]thymidine incorporation and protein content per cell. The levels of the VDR protein remarkably increased in comparison with control cells, except for the incubation with 9-cis retinoic acid. This increase was particularly accentuated in C2C12 cells treated with KH 1060 and 9-cis retinoic acid in combination. These results, taken together, suggest a role for vitamin D derivatives and retinoids on C2C12 cells.     

Hepatic metabolism of retinoids and disease associations

The liver is the most important tissue site in the body for uptake of postprandial retinoid, as well as for retinoid storage. Within the liver, both hepatocytes and hepatic stellate cells (HSCs) are importantly involved in retinoid metabolism. Hepatocytes play an indispensable role in uptake and processing of dietary retinoid into the liver, and in synthesis and secretion of retinol-binding protein (RBP), which is required for mobilizing hepatic retinoid stores. HSCs are the central cellular site for retinoid storage in the healthy animal, accounting for as much as 50-60% of the total retinoid present in the entire body. The liver is also an important target organ for retinoid actions. Retinoic acid is synthesized in the liver and can interact with retinoid receptors which control expression of a large number of genes involved in hepatic processes. Altered retinoid metabolism and the accompanying dysregulation of retinoid signaling in the liver contribute to hepatic disease. This is related to HSCs, which contribute significantly to the development of hepatic disease when they undergo a process of cellular activation. HSC activation results in the loss of HSC retinoid stores and changes in extracellular matrix deposition leading to the onset of liver fibrosis. An association between hepatic disease progression and decreased hepatic retinoid storage has been demonstrated. In this review article, we summarize the essential role of the liver in retinoid metabolism and consider briefly associations between hepatic retinoid metabolism and disease. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism.     

Synthetic retinoids in dermatology

The potential of vitamin A, or retinol, in the treatment of a variety of skin diseases has long been recognized, but because of serious toxic effects this substance generally could not be used. The recent development and marketing of two relatively nontoxic synthetic analogues, which are known as retinoids, has made it possible to treat some of the diseases that are resistant to standard forms of therapy. Isotretinoin is very effective in cystic and conglobate acne, while etretinate is especially useful in the more severe forms of psoriasis. Good results have also been obtained in other disorders of keratinization. Vitamin A and its derivatives apparently have an antineoplastic effect as well and may come to be used in both the prevention and the treatment of epithelial cancer. In many of these diseases the retinoids act by enhancing the normal differentiation and proliferation of epidermal tissues, but the exact mechanisms are not well understood. Their influence on the intracellular polyamines that control the synthesis of nucleic acids and proteins may be an important factor. Although the retinoids have few serious systemic effects, they are teratogenic, and because they persist in the body their use in women of childbearing potential is limited.     

Solubility of retinoids in water

Spectrophotometric and radioactive techniques were used to measure the water solubility of retinaldehyde, retinol (vitamin A), and retinoic acid under physiological conditions. Hydration decreases the molar extinction coefficient of these substances and shifts their absorption peak bathochromically (10 nm for retinal and approximately 1 nm for the rest). We find their solubility to be about 0.1 microM at room temperature, pH 7.3 (with experimental values being 0.11 microM for retinaldehyde, 0.06 microM for retinol, and 0.21 microM for retinoic acid). To prevent oxidative degradation of retinol, which is the most labile retinoid, our argon-saturated buffer solutions contained physiological levels of ascorbate or alpha-tocopherol. To the best of our knowledge, water solubility of these compounds has not yet been previously reported. Although the measured solubilities are relatively low, they are significant and may account for the movement of retinoids through the aqueous phase as observed by others during exchange with binding proteins and during intervesicular transfer in the absence of binding proteins. Diffusion of uncomplexed retinoids through the aqueous phase can be a major pathway for transport over subcellular distances.     

Interaction of fatty acids,acyl-CoA derivatives and retinoids with microsomal membranes: effect of cytosolic proteins

This paper reviews characteristics of microsomal membrane structure; long chain fatty acids, acyl CoA derivatives, retinoids and the microsomal formation of acyl CoA derivatives and retinyl esters. It is analyzed how the movement of these molecules at the intracellular level is affected by their respective binding proteins (Fatty acid binding protein, acyl CoA binding protein and cellular retinol binding protein). Studies with model systems using these hydrophobic ligands and the lipid-binding or transfer proteins are also described. This topic is of interest especially because in the esterification of retinol the three substrates and the three binding proteins may interact. (Mol Cell Biochem20: 89–94, 1993)Abbreviations FABP(s) Fatty Acid Binding Protein(s) - CRBP Cellular Retinol Binding Protein - ACBP Acyl-CoA-Binding Protein