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Caspase inhibitors and regulation of the IL-1 family cytokines
 Brabcová, Eva ; Stříž, Ilja (advisor) ; Holáň, Vladimír (referee)
Proinflammatory cytokines from IL-1 family play a key role in immune and immunopathological reactions and are involved also in initial phases of rejection mechanisms. One of their multiple functions is the induction of chemokines attracting immune cells into the site of injury. The aim of our study was to assess the effect of proinflammatory cytokines on the chemokine release and mRNA induction in epithelial cell lines of renal and lung origin. Furthermore, we tested the effect of caspase-1 inhibitors isolated from Streptomyces nodus (manumycin, asukamycin, MM273) on the release of IL-1 beta and IL-18 from human macrophages. These cytokines are cleaved into their active form by caspase-1 and inihibtion of the enzyme activity might be a perspective therapeutical approach to reduce inflammatory reaction. In our experimental model, we used cell line derived from renal adenocarcinoma (RA), A549 cell line (alveolar type II-like cells), and THP-1 monocyte/macrophage cell line. Chemokine mRNA induction was evaluated by an oligoarray and chemokine and cytokine levels were measured by Luminex or ELISA technology. Our data have showed that both epithelial cell lines produced constitutively mainly CXC chemokines attracting neutrophils (CXCL5/ENA-78, CXCL8/IL-8) and some of the CC chemokines characteristic for the...
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