1. Peracetylated hydroxytyrosol, a new hydroxytyrosol derivate, attenuates LPS-induced inflammatory response in murine peritoneal macrophages via regulation of non-canonical inflammasome, Nrf2/HO1 and JAK/STAT signaling pathways.
- Author
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Montoya, Tatiana, Aparicio-Soto, Marina, Castejón, María Luisa, Rosillo, María Ángeles, Sánchez-Hidalgo, Marina, Begines, Paloma, Fernández-Bolaños, José G., and Alarcón-de-la-Lastra, Catalina
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HYDROXYTYROSOL , *PERITONEAL macrophages , *INFLAMMASOMES , *CELLULAR signal transduction , *ENZYME-linked immunosorbent assay , *PROTEIN metabolism , *ANIMAL experimentation , *CARRIER proteins , *COMPARATIVE studies , *CYTOKINES , *ETHANOL , *INFLAMMATION , *MACROPHAGES , *RESEARCH methodology , *MEDICAL cooperation , *MEMBRANE proteins , *METABOLISM , *MICE , *NITRITES , *NONSTEROIDAL anti-inflammatory agents , *OXIDOREDUCTASES , *PROTEINS , *RESEARCH , *TRANSFERASES , *EVALUATION research , *LIPOPOLYSACCHARIDES , *JANUS kinases , *PHARMACODYNAMICS - Abstract
The present study was designed to investigate the anti-inflammatory effects of a new derivative of hydroxytyrosol (HTy), peracetylated hydroxytyrosol (Per-HTy), compared with its parent, HTy, on lipopolysaccharide (LPS)-stimulated murine macrophages as well as potential signaling pathways involved. In particular, we attempted to characterize the role of the inflammasome underlying Per-HTy possible anti-inflammatory effects. Isolated murine peritoneal macrophages were treated with HTy or its derivative in the presence or absence of LPS (5 μg/ml) for 18 h. Cell viability was determined using sulforhodamine B (SRB) assay. Nitric oxide (NO) production was analyzed by Griess method. Production of pro-inflammatory cytokines was evaluated by enzyme-linked immunosorbent assay (ELISA) and inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway (STAT3), haem oxigenase 1 (HO1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression and mitogen-activated protein kinases (MAPKs) activation was determined by Western blot. Per-HTy significantly reduced the levels of NO and pro-inflammatory cytokines as well as both COX-2 and iNOS expressions. Furthermore, Per-HTy treatment inhibited STAT3 and increased Nrf2 and HO1 protein levels in murine macrophages exposed to LPS. In addition, Per-HTy anti-inflammatory activity was related with an inhibition of non-canonical nucleotide binding domain (NOD)-like receptor (NLRP3) inflammasome pathways by decreasing pro-inflammatory interleukin (IL)-1β and IL-18 cytokine levels as consequence of regulation of cleaved caspase-11 enzyme. These results support that this new HTy derivative may offer a new promising nutraceutical therapeutic strategy in the management of inflammatory-related pathologies. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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