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Abstract: Background. The immune response to Helicobacter pylori importantly determines the outcome of infection as well as the success of eradication therapy. We demonstrate the role of a cysteine protease cathepsin X in the immune response to H. pylori infection. Materials and methods. We analysed how the inhibition of cathepsin X influenced the immune response in experiments when THP-1 cells or dendritic cells isolated from patients were stimulated with 48 strains of H. pylori isolated from gastric biopsy samples of patients which had problems with the eradication of bacteria. Results. The experiments, performed with the help of a flow cytometer, showed that the expression of Toll-like receptors (TLRs), especially TLR-4 molecules, on the membranes of THP-1 cells or dendritic cells was higher when we stimulated cells with H. pylori together with inhibitor of cathepsin X 2F12 compared to THP-1 cells or dendritic cells stimulated with H. pylori only, and also in comparison with negative control samples. We also demonstrated that when we inhibited the action of cathepsin X in THP-1 cells, the concentrations of pro-inflammatory cytokines were lower than when THP-1 cell were stimulated with H. pylori only. Conclusions. We demonstrated that inhibition of cathepsin X influences the internalization of TLR-2 and TLR-4. TLR-2 and TLR-4 redistribution to intra-cytoplasmic compartments is hampered if cathepsin X is blocked. The beginning of a successful immune response against H. pylori in the case of cathepsin X inhibition is delayed.
Keywords: cathepsin X, macrophage, dendritic cells
Published in DiRROS: 22.03.2024; Views: 73; Downloads: 40
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Abstract: Tumor vaccines have several potential advantages over standard anticancer regirrcents. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tccmor aaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which imrrtune tolerance exists. That is why the population of tumor-specific lymphocytes is represented by a small number of low-affinity T-lymphocytes that induce weak antitumor immune response. Simultaneously, tumors evolve many mechanisms to actively evade immune system,what makes them poorly immunogenic or even tolerogenic. Novel irrtmunotherapeutic strategies are directed toward breaking immune tolerance to tumor antigens, enhancing immunogenicity of tumor vaccines and overcoming mechanisms of tumor escape. There are several approaches, unfortunately, all of them still far away from an ideal tumor vaccine that would reject a tumor. Difficulties in the activation of antitumor immune response by tumor vaccines have led to the development of alternative immunotherapeutic strategies that directly focus on effector mechanisms of immune system (adoptive tumor-specific T-lymphocyte transfer and tumor specific monoclonal antibodies).
Published in DiRROS: 15.02.2024; Views: 126; Downloads: 31
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Abstract: Flow cytometry has been introduced as the most reliable method for the analysis of lymphocyte subsets. The advantage of flow cytometry is that it enables application of virtually all monoclonal antibodies (native cells), a quantitative estimation of different lymphoid cells, and that cell can be simultaneously analysed for multiple marker expression. The usage of flow cytometers requiers considerable knowledge of physics and its technical application. Moreover, several problems arise from the complexity of the biolocal systems investigated.
Published in DiRROS: 19.01.2024; Views: 142; Downloads: 35
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Published in DiRROS: 31.03.2020; Views: 1272; Downloads: 386
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