M Ayoub

University of Freiburg, Freiburg, Baden-Wuerttemberg, Germany

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Publications (6)8.32 Total impact

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    ABSTRACT: Vaccination with the antiallergic drug Histaglobin is used to treat a broad range of human allergic diseases including bronchial asthma, allergic rhinitis, and atopic dermatitis. In order to further elucidate its functional activity, Histaglobin was investigated in an in vivo mouse allergy model. Mice were sensitized with ovalbumin either prior to or after Histaglobin treatment, and its antiallergic potential was evaluated. Ovalbumin-sensitized mice exhibited increased serum levels of IL-4, tumor necrosis factor alpha (TNF-alpha), and an increase of total and ovalbumin-specific IgE; total and ovalbumin-specific IgG levels were also elevated. Subsequent administration (therapeutic treatment) of Histaglobin resulted in a decrease of total and specific serum IgE levels; total and specific IgG1 serum levels were reduced by more than 50% and 45%, respectively; the mice displayed a down-regulation of IL-4 and TNF-alpha serum levels and showed increased levels of IFN-gamma and IgG2a. Mice pretreated with Histaglobin, prior to ovalbumin sensitization (prophylactic treatment), were found to be widely unresponsive to ovalbumin. They exhibited higher serum levels of IFN-gamma and IgG2a (total and specific) compared to saline-treated control mice. The inhibitory effects were still observed 1 month post-immunization. Our data, indicating a Histaglobin-induced modulation of the Th1/Th2 balance in favour of Th1, correspond with the well-known antiallergic activity of Histaglobin observed in patients.
    International Immunopharmacology 05/2003; 3(4):523-39. · 2.42 Impact Factor
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    ABSTRACT: Synthetic lipopeptides based on bacterial lipoprotein are efficient activators for monocytes/macrophages inducing the release of interleukin (IL)-1, IL-6, tumour necrosis factor-alpha (TNF-alpha), reactive oxygen/nitrogen intermediates, and the translocation of nuclear factor kappaB (NFkappaB). In this report we investigate the signal transduction pathways involved in leucocyte activation by the synthetic lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-(R)-cysteinyl-seryl-(lysyl)3-lysine (P3CSK4). We show that P3CSK4 activates mitogen-activated protein (MAP)-kinases ERK1/2 and MAP kinase (MAPK)-kinases MEK1/2 in bone-marrow-derived macrophages (BMDM) and in the macrophage cell line RAW 264.7. Additionally, we could detect differences between the P3CSK4 and lipopolysaccharide (LPS)-induced phosphorylation of MAP kinases: Different levels in phosphorylation were found both in kinetics and dose-response using RAW 264.7 cells or BMDM from BALB/c and LPS responder mice (C57BL/10ScSn) or LPS non-responder mice (C57BL/10ScCr). The lipopeptide activated the MAPK-signalling cascade in both LPS responder and non-responder macrophages, whereas LPS induced the MAPK signalling pathway only in macrophages derived from LPS responder mice. An approximately 70% decrease of lipopeptide induced NFkappaB translocation and an about 50% reduction of nitric oxide (NO) release was observed in the presence of anti-CD14. These data correspond to the reduction of phosphorylation of ERK1/2 after stimulation with P3CSK4 in the presence of anti-CD14 antibodies. Inhibition of MEK1/2 by PD98059 completely reduced the lipopeptide-induced phosphorylation of ERK1/2 indicating that MEK1/2 are solely responsible for the phosphorylation of the downstream-located MAP kinases ERK1/2.
    Immunology 06/2001; 103(1):49-60. · 3.71 Impact Factor
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    ABSTRACT: Lactate dehydrogenase catalyzes the final step in glycolysis, the interconversion of pyruvate and lactate. The tetrameric enzyme is composed of one or two subunits (H and/or M) resulting in five isoenzyme forms: LDH-H4, -H3M1, -H2M2, -H1M3, and -M4. The relative distribution of the LDH isoenzymes is tissue dependent and a significant marker for the diagnosis of hepatoma of the liver, myocardial infarction, muscular dystrophy, and a wide variety of other acute and chronic diseases to be detected by alterations of the LDH isoenzyme pattern in serum. Immunochemical approaches to the routine determination of LDH depend on isoenzyme specific antibodies. Since the H- and M-subunits for human LDH are highly homologous, LDH isoenzyme specific antibodies for immunochemical monitoring are hard to generate. Here we present data on the generation and characterization of LDH isoenzyme-specific mono- and polyclonal antibodies in different species in the presence of lipopeptide adjuvants. Western-Blot and ELISA analysis showed that antisera and monoclonal antibodies recognize their homologous antigens with high specificity and are therefore suitable for immunochemical monitoring of the LDH isoenzymes H4 and M4. In addition, they can be used for the determination of LDH isoenzyme specific activity which is an essential prerequisite for online amperometric immunosensor monitoring.
    European journal of medical research 02/2001; 6(1):10-20. · 1.10 Impact Factor
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    ABSTRACT: Synthetic lipopeptides derived from the N-terminus of bacterial lipoprotein constitute potent macrophage activators and polyclonal B-lymphocyte stimulators. They are also efficient immunoadjuvants in parenteral, oral and nasal immunization either in combination with or after covalent linkage to an antigen. Here we show how alterations in the molecular structure influence their biological properties indicating P3CSK4 as one of the most active members of a lipopentapeptide fatty acid library. This compound resulted in a most pronounced macrophage stimulation as indicated by NO release, activation of NFkappaB translocation, and enhancement of tyrosine protein phosphorylation. Furthermore, P3CSK4 activates/represses an array of at least 140 genes partly involved in signal transduction and regulation of the immune response. Finally we have evidence that P3CSK4 constitutes an effective adjuvant for DNA immunizations, especially increasing weak humoral immune responses. Our findings are of importance for further optimizing both conventional and genetic immunization, and for the development of novel synthetic vaccines.
    International Journal of Immunopharmacology 01/2001; 22(12):1093-102.
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    ABSTRACT: The transcription factor NF-κB is the central regulator for the expression of various genes involved in inflammation, infection and immune response including the genes for IL-1β, TNF-α, IL-6 and leukocyte adhesion molecules. Here, we show that the anti-allergic drug histaglobin down-regulates the release of IL-1β, TNF-α, IL-6 and IL-10 in human peripheral blood mononuclear cell cultures. This down-regulatory effect becomes even more pronounced when the cultures are simultaneously activated with the T-lymphocyte mitogen phytohemagglutinin (PHA) or with the B-lymphocyte and macrophage activator lipopeptide (P3CSK4). We also demonstrate that histaglobin inhibits the nuclear translocation of NF-κB in response to TNF-α or lipopolysaccharide (LPS) in bone marrow-derived macrophages of Balb/c mice. The inhibitory effect of histaglobin on NF-κB activation and cytokine release might be responsible for its anti-allergic effect as demonstrated in clinical studies.
    International Journal of Immunopharmacology 11/2000;
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    ABSTRACT: The bacterial extract OM-89 used for the prevention and treatment of recurrent urinary tract infections constitutes an effective immunostimulant in vitro and in vivo. Here we demonstrate that OM-89 shows mitogenic properties towards murine spleen cell cultures from LPS responder and non-responder mice. In macrophages the extract induces the translocation of NF-kappaB into the cell nucleus and RNI (radical nitrogen intermediates) release, which could be attributed to single fractions of the extract. Our findings on the in vitro immunostimulatory effect of OM-89, as well as its immunogenic and adjuvant properties, are of importance for understanding its therapeutic efficacy as demonstrated in clinical studies.
    European journal of medical research 04/2000; 5(3):101-9. · 1.10 Impact Factor