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Role of IL-34 in the pathogenesis of autoimmune rheumatic diseases
Reichlová, Petra ; Andrés Cerezo, Lucie (advisor) ; Brdička, Tomáš (referee)
Interleukin-34 (IL-34) is a cytokine described in 2008 using proteomic analysis. As IL-34 does not share any sequence similarity with other interleukins, it fell into the group so-called "orphan" cytokines. IL-34 binds to three receptors: CSF-1R, syndecan-1 and PTP-ζ. These interactions influence signal pathways which lead to proliferation, differenciation of monocytes or to an increased expression of other cytokines. Up-regulated expression of IL-34 has been observed in many autoimmune rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, Sjögrenʼs syndrome or systemic scleroderma. These findings indicate that IL- 34 may be involved in the pathogenesis of these diseases and may become one of the diagnostic markers or even the target of medical therapy in the future. Key words: interleukin-34, cytokine, autoimmune rheumatic diseases, rheumatoid arthritis, systemic scleroderma, systemic lupus erythematosus, Sjögrenʼs syndrome
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The role of S100 proteins in the pathogenesis of rheumatic diseases
Andrés Cerezo, Lucie ; Šenolt, Ladislav (advisor) ; Hrnčíř, Zbyněk (referee) ; Horák, Pavel (referee)
Introduction: Recent findings and better understanding to the pathogenesis of rheumatic diseases contributed to the development of biological therapies targeting cytokines and immune cells. Several S100 proteins exert cytokine-like effects and participate in the regulation of the inflammatory process. The aim of this work was to study the role of selected S100 proteins in the activity and in the pathogenesis of the rheumatic diseases. Results: Our data show for the first time an association of S100A4 proteinwith RA disease activity and decrease of the bioactive form, but not the total amount of S100A4, after aplication of tumour necrosis factor (TNF) blocking biologic therapy in patients with RA. We demonstrated that in vitro S100A4 acts as a potent pro-inflammatory mediator inducing production of TNFα, interleukin (IL)-1β and IL-6 in PBMCs via Toll-like receptor 4 (TLR-4), transcription factor NFκB and tyrosine kinases erk1/2 and p38. Moreover, S100A4 can play an important role in the pathogenesis of inflammatory myopathies. S100A4 is present in the inflammatory infiltrate of the affected muscles and in the regenerating muscles and may act as a cytokine-like factor indirectly promoting muscle fiber damage by stimulating mononuclear cells to increase the synthesis of pro-inflammatory cytokines. We...
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The role of S100A11 protein (calgizzarin) in rheumatoid arthritis pathogenesis
Navrátilová, Adéla ; Andrés Cerezo, Lucie (advisor) ; Štěpánek, Ondřej (referee)
Rheumatoid arthritis (RA) is a systemic connective tissue autoimmune disease which is characterized by persistent inflammation of the synovial tissue, joint destruction and visceral organs and vessels damage. The RA joint environment contains pro-inflammatory molecules and immune cells. Small calcium-binding proteins of the S100 family are also known to be involved in the inflammatory process of RA, and some of them have been studied in our laboratory. One member of this family, S100A11 (calgizzarin), is well described in oncological diseases but its role in autoimmune diseases has not yet been described. Neutrophil extracellular traps (NETs), which are a potential source of autoantigens and immunoactive molecules, also contribute to the chronic inflammatory process in RA. The aim of our study was to investigate S100A11 with the focus on its role in the processes of inflammation and tissue destruction and to assess its possible association with NETs. Using in vitro experiments and molecular methods (reverse transcription, quantitative polymerase chain reaction (qPCR) and multiplex assay) we have shown that S100A11 exerts its pro-inflammatory effect on mononuclear cells via toll-like receptor (TLR)-4, however there was not any significant effect of S100A11 on the production of pro-inflammatory...
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The role of S100 proteins in the pathogenesis of rheumatic diseases
Andrés Cerezo, Lucie ; Šenolt, Ladislav (advisor) ; Hrnčíř, Zbyněk (referee) ; Horák, Pavel (referee)
Introduction: Recent findings and better understanding to the pathogenesis of rheumatic diseases contributed to the development of biological therapies targeting cytokines and immune cells. Several S100 proteins exert cytokine-like effects and participate in the regulation of the inflammatory process. The aim of this work was to study the role of selected S100 proteins in the activity and in the pathogenesis of the rheumatic diseases. Results: Our data show for the first time an association of S100A4 proteinwith RA disease activity and decrease of the bioactive form, but not the total amount of S100A4, after aplication of tumour necrosis factor (TNF) blocking biologic therapy in patients with RA. We demonstrated that in vitro S100A4 acts as a potent pro-inflammatory mediator inducing production of TNFα, interleukin (IL)-1β and IL-6 in PBMCs via Toll-like receptor 4 (TLR-4), transcription factor NFκB and tyrosine kinases erk1/2 and p38. Moreover, S100A4 can play an important role in the pathogenesis of inflammatory myopathies. S100A4 is present in the inflammatory infiltrate of the affected muscles and in the regenerating muscles and may act as a cytokine-like factor indirectly promoting muscle fiber damage by stimulating mononuclear cells to increase the synthesis of pro-inflammatory cytokines. We...
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