Levels Of DP Research Articles

Inhibitors of dipeptidyl peptidase IV/CD26 suppress activation of human MBP-specific CD4+ T cell clones

The ectoenzyme dipeptidyl peptidase IV (DP IV, EC 3.4.14.5, CD26) has been shown to play a crucial role in T cell activation. Specific inhibitors of DP IV suppress DNA synthesis as well as cytokine production (IL-2, IL-10, IL-12, IFN- γ) of stimulated human and mouse T cells suggesting a potential application of these effectors in transplantations and autoimmune diseases. In the present study, we have examined the expression of DP IV/CD26 on six myelin basic protein (MBP)(87–99)-specific, CD4+ T cell clones (TCC) derived from patients with multiple sclerosis (MS) as well as the biological effects of the two synthetic DP IV inhibitors Lys[Z(NO 2)]-thiazolidide and Lys[Z(NO 2)]-pyrrolidide on the function of these cells. All TCC expressed high levels of DP IV/CD26, as shown by flow cytometry and by enzymatic DP IV assay. Enzymatic activity of resting TCC was found to be three to fourfold higher than on resting peripheral blood T cells and close to that of T cells 48 h after PHA stimulation. The DP IV inhibitors suppress DNA synthesis and IFN- γ, IL-4, and TNF- α production of the antigen-stimulated TCC. These data suggest that CD26 plays a role in regulation of activation of autoreactive TCC. Further in-vivo investigations, first in experimental models, will clarify, whether the inhibition of the enzymatic activity of DP IV could be a useful tool for therapeutic interventions in MS or other autoimmune diseases.

CD26 is involved in regulation of cytokine production in natural killer cells.

Dipeptidyl peptidase IV (DP IV, CD26) is a postproline cleaving enzyme which catalyses the degradation of polypeptides from the N-terminal part. DP IV is expressed on the surface of cells from several tissues. High levels of DP IV activity were found in the brush border membrane of the intestinal epithelium, in the proximal tubulus of the kidney, and in the serum [1,2]. In the immune system, DP IV was observed to be expressed on activated T cells, on activated NK cells, and on activated B lymphocytes [3,4]. DP IV was characterised as a key enzyme in the regulation of activation and proliferation of T lymphocytes. The mitogen- and antigen-induced DNA synthesis was found to be inhibited by specific DP IV inhibitors [5]. Earlier we described the expression of DP IV/CD26 on activated NK cells using enzymatic and immunologic techniques. Moreover, evidence was presented that DP IV is involved in the regulation of DNA synthesis and cell cycle progression, but not in that of the natural cytotoxic activity of NK cells against K 562 cells. The mechanisms of regulation of the DNA synthesis are unclear as yet. In T lymphocytes it could be shown that DP IV inhibitors specifically regulate the cytokine production of these cells and by that means affect the autocrine growth regulation [6]. It was shown that both resting and activated NK cells are capable of cytokine production [7,8]. These cytokines seem to play a role in regulation of NK cell activation as well as in their effector functions [9]. Other authors postulated a link between CD26 expression and apoptosis [10].KeywordsNatural Killer CellHuman Immunodeficiency Virus TypeActivate Natural Killer CellBrush Border MembraneDipeptidyl PeptidaseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Effects of Skin Fermentation Time on the Phenols, Anthocyanins, Ellagic Acid Sediment, and Sensory Characteristics of a RedVitis rotundifoliaWine

Noble muscadine grapes (<i>Vitis rotundifolia</i>) were harvested at two stages of maturity (optimum, based on full color and flavor development and pH below 3.3, and 14 days later) and either pressed immediately for a blush wine or fermented on the skins for two, four, or six days. Red wines from more mature grapes had greater color intensity and higher levels of anthocyanins, total phenols, and non-polymeric phenols. Wines from the more mature grapes had higher levels of the 3,5-diglucosides of peonidin (Pn) and malvidin (Mv), and lower levels of delphinidin (Dp), cyanidin (Cy), and petunidin (Pt). Maximum color and anthocyanin extraction occurred within four days of skin fermentation with the optimum maturity fruit, but continued through day six with later maturity fruit. However, wines fermented on the skins for four or six days had less muscadine aroma intensity and were more astringent. Skin fermentation time had little effect on the distribution of anthocyanins, although the immediate press wines had lower levels of Dp and Mv and higher levels of Cy and Pn. Total, non-polymeric and polymeric phenol levels increased with increasing skin fermentation time, but the polymeric phenol levels and anthocyanin polymerization were generally low in all wines.

Distribution of desmosomal proteins in F9 embryonal carcinoma cells and epithelial cell derivatives.

In diverse epithelia, cytoskeletal keratin intermediate filaments (IFs) associated with the cytoplasmic face of intercellular junctional desmosomes. The processes underlying desmosome formation and keratin IF interactions remain unclear. We have examined F9 embryonal carcinoma (EC) cell differentiation as a model for embryonic development of epithelial surface desmosomes. As determined by immunofluorescence microscopy and biochemical protein techniques, F9 EC cells, which lack surface desmosomes and keratin IFs, express the desmosomal proteins desmoplakins I and II (DP I/II), desmoglein I (DG I) and plakoglobin (PK). DP I/II are present at low level and are relatively soluble in buffer containing Triton X-100. Immunofluorescence localizes DP I/II to the juxtanuclear, centrosomal region. Species of DG I and PK are detected in both the Triton X-100-soluble and -insoluble protein fractions. DG I appears dispersed throughout the cell while PK resides at cell-cell boundaries. In epithelial cell cultures induced by retinoic acid (RA) treatment, each of the desmosomal proteins is organized into punctate desmosome-like structures with the appearance of simple epithelial K8/K18 IFs. The steady-state levels of DP I/II and PK increase with a partitioning of the majority of the desmosomal components into the insoluble fraction. In epithelial cells which lack distinct surface desmosomes, an intracellular association of keratin bundles with DP I/II is observed, suggesting that keratin filaments may facilitate the translocation of these desmosomal components to the cell surface. Parietal endoderm-like cells, derived by treatment with RA and dibutyryl cAMP, are analogous to F9 EC cells in that the cells express desmosomal components and do not display surface desmosomes. Moreover, K8 and K18 do not form distinct filaments, and the protein and RNA levels of K8 are low relative to epithelial cells induced by RA alone. The F9 system appears to be a relevant model for studies of desmosome assembly and the potential interactions of desmosomal proteins and keratin IFs in embryonic epithelial cell types.

Increases in HLA-DQ, DP, DR, and Transferrin Receptors on Alveolar Macrophages in Sarcoidosis and Allergic Alveolitis Compared with Fibrosing Alveolitis

We have used flow cytometric methods to detect and quantify HLA-DR, DQ, and DP antigens and transferrin receptors on alveolar macrophages in lavage samples from 36 patients with granulomatous lung diseases (extrinsic allergic alveolitis [EAA], n = 13; sarcoidosis, n = 23), and 12 patients having fibrosing alveolitis (FA) (cryptogenic fibrosing alveolitis, n = 3; FA and scleroderma, n = 8; FA and primary biliary cirrhosis, n = 1). HLA-DR, DQ, and DP antigens were expressed on the majority of alveolar macrophages in all the patients, and the percentages of positive cells were similar to those in control subjects without lung disease. However, the amounts expressed were higher in those with EAA and sarcoidosis than in the FA group or control subjects, the most significant differences being in HLA-DQ and HLA-DP expression. Transferrin receptor expression was also higher in the granulomatous lung diseases. In sarcoidosis, higher levels of HLA-DQ correlated with lower lung function measurements (Dco p less than 0.025, FVC p less than 0.025, FEV1 p less than 0.005), suggesting this may be a marker of disease activity. HLA-DP levels also showed a trend (p less than 0.1) of inverse correlation with lung function. Levels of HLA-DQ (p less than 0.005) and HLA-DP (p less than 0.001) correlated more closely than HLA-DR with numbers of lymphocytes in the lavage fluids, and HLA-DQ levels correlated with increasing proportions of lymphocytes in proliferation (p less than 0.05). We suggest that high levels of HLA-DQ and DP on alveolar macrophages may be more relevant than HLA-DR to the enhanced antigen-presenting function of these cells in sarcoidosis, and possibly also in EAA.

High rate of HLA class II mRNA synthesis in rheumatoid arthritis joints and its persistence in culture: down-regulation by recombinant interleukin 2.

The expression of HLA class II mRNA was investigated in the joints of patients with active rheumatoid arthritis (RA) in order to evaluate patterns of synthesis. Northern hybridization analysis showed that HLA class II gene transcripts in RA joints were of the correct sizes, and subsequent analyses were performed by slot blotting. All active RA samples expressed high levels of HLA-DR, DP, and DQ mRNA with DP and DQ less than DR. Synovial fluid or membrane cells, chiefly a mixture of T cells and macrophages, were placed in culture, in the absence of any stimulation. The levels of mRNA remained at a high level in vitro. The half of HLA-DR mRNA in joint cells was very brief (approximately 30 min), indicating that prolonged synthesis was due to restimulation of the cells. The effect of lymphokines on HLA class II regulation on joint cell was assessed. Gamma interferon was capable of augmenting HLA-DR to some extent, but paradoxically interleukin 2 at concentrations optimal for stimulating T cells, diminished HLA-DR expression.

Gamma interferon induces detectable serological and functional expression of DR and DP but not DQ antigens on cultured amniotic fluid cells.

Cultured amniotic fluid cells, which are used for HLA typing studies for the prenatal diagnosis of HLA linked diseases and for prenatal determination of paternity, usually contain mixtures of fibroblastic and epithelioid cells. Cells of both types lack constitutive expression of HLA class II antigens, but these can be induced by pretreatment with gamma interferon. Both serological and functional studies indicate that detectable levels of DR and DP but not DQ antigens can be thereby induced. DR and DP cannot, however, be induced on chorionic villus cells.

Performance Properties of Cottons at Two Levels of Durable-Press and Conditioned Wrinkle-Recovery Angles

Polymerization-crosslinking reagents such as N-methylolacrylamide, N-methylol- methacrylamide, and N-methylolpolyethyleneurea (dp = 3) (NMP-2) and conven tional crosslinking agents such as dimethylolethyleneurea, dimethyloldihydroxyethyl eneurea, and formaldehyde were used to treat cotton twill fabrics. A concentration study with these reagents was carried out, and physical and chemical properties of the finished fabrics were compared. Strength and abrasion properties of treated fabrics at two levels of DP and conditioned WRA were also determined. The results indicated that the experimental reagents capable of undergoing polymerization as well as crosslinking within the cellulose substrate afford a superior balance of strength and abrasion properties. NMP-2 appears to be most stable to loss of formaldehyde among the polymer-forming reagents studied and most sensitive to loss of breaking strength from scorching following treatment with chlorine bleach.

Temperature-stress-induced Production of Abscisic Acid and Dihydrophaseic Acid in Warm- and Coolseason Crops1

Abstract Abscisic acid (ABA) metabolism of 6-week-old seedlings of cool- and warm-season crops was determined after a 24-hr exposure to supra- and sub-optimal temperatures. Plants were grown at 25°C and then exposed to 10, 25, or 40°C. After a 24-hr exposure, free (FABA) and hydrolyzable (HABA) abscisic acid and dihydrophaseic acid (DPA) were measured in the plant tops by gas chromatography. Warm-season crops, exposed to 10°C exhibited elevated levels of FABA, HABA and DP A compared to those plants exposed to 25 or 40°C. Among cool-season crops, only peas had higher FABA and HABA levels at 40°C than at 10 or 25°C, while beets had lower levels of HABA at 25°C than at 10 or 40°C. DPA existed at much higher concentrations than FABA and HABA in all plants. The increases in ABA and DPA in warm-season crops exposed to 10°C are attributed to low temperature stress.