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THP-1 Macrophages (thp-1 + macrophage)
Selected Abstracts8-isoprostane increases scavenger receptor A and matrix metalloproteinase activity in THP-1 macrophages, resulting in long-lived foam cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2004H. Scholz Abstract Background, Oxidative stress is a key factor in atherogenesis, in which it is closely associated with the inflammation and formation of bioactive lipids. Although 8-isoprostane is regarded as a reliable marker of oxidative stress in vivo, the pathogenic role of this F2 -isoprostane in atherogenesis is far from clear. Based on the important role of foam cells in the initiation and progression of atherosclerosis we hereby examined the ability of 8-isoprostane to modulate oxidized (ox)LDL-induced foam cell formation and the function of these cells, particularly focusing on the effect on matrix degradation. Methods and results, 8-isoprostane (10 µM) augmented the oxLDL-induced (20 µg mL,1) lipid accumulation of THP-1 macrophages evaluated by Oil-Red-O staining and lipid mass quantification (colourimetric assay). Additionally, 8-isoprostane induced the expression of the scavenger receptor A type 1 (MSR-1) [mRNA and protein level], assessed by RT-PCR and Western blotting, respectively. Moreover, 8-isoprostane counteracted the oxLDL-induced apoptosis of these cells, involving both mitochondrial-protective and caspase-suppressive mechanisms. Along with these changes, 8-isoprostane increased the oxLDL-induced gene expression of matrix metalloproteinase (MMP)-9 and its endogenous inhibitor [i.e. tissue inhibitor of MMP (TIMP)-1] accompanied by enhanced total MMP activity. Conclusions, We show that 8-isoprostane increases foam cell formation at least partly by enhancing MSR-1 expression and by inhibiting apoptosis of these cells, inducing long-lived foam cells with enhanced matrix degrading capacity. Our findings further support a role for 8-isoprostane not only as a marker of oxidative stress in patients with atherosclerotic disorders, but also as a mediator in atherogenesis and plaque destabilization. [source] Ascochlorin suppresses oxLDL-induced MMP-9 expression by inhibiting the MEK/ERK signaling pathway in human THP-1 macrophagesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2007Jeong Han Kang Abstract The critical initiating event in atherogenesis involves the invasion of monocytes through the endothelial walls of arteries and the transformation of monocytes from macrophages into foam cells. Human THP-1 monocytic cells can be induced to differentiate into macrophages by phorbol myristate acetate (PMA) and can then be converted into foam cells by exposure to oxidized low-density lipoprotein (oxLDL). Also, during a chronic inflammatory response, monocytes/macrophages produce the 92-kDa matrix metalloproteinase-9 (MMP-9) that may contribute to the extravasation, migration, and tissue remolding capacities of the phagocytic cells. Here, we investigate the effect of ascochlorin (ASC), a prenylphenol antiviral compound from the fungus Ascochyta viciae, on oxLDL-induced MMP-9 expression and activity in human THP-1 macrophages. ASC reduced oxLDL-induced MMP-9 expression and activity in a time-dependent and dose-dependent manner. Also, an analysis of MMP-9 activity using pharmacologic inhibitors showed that ASC inhibits MMP-9 activity via the extracellular signal-regulated kinase 1 and kinase 2 pathways. Our results suggest that ASC may be useful as a potent clinical antiatherogenic agent, a topic of considerable interest in the biological chemistry of chemotherapeutic agents. J. Cell. Biochem. 102: 506,514, 2007. © 2007 Wiley-Liss, Inc. [source] Activation of NF-KB signalling and TNF,-expression in THP-1 macrophages by TiAlV- and polyethylene-wear particlesJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2005Bernd Baumann Abstract Wear particles are believed to induce periprosthetic inflammation which contributes to periprosthetic osteolysis. TNF, plays a pivotal role in the pathogenesis of this process. The molecular mechanisms leading to the development of periprosthetic inflammation with upregulated TNF, expression in monocytic cells in response to different wear particles have yet to be defined. In this study we evaluated the effects of polyethylene- and TiAlV-particles on activation of NF-kB signalling pathways and TNF, biosynthesis and release in monocytic cells with respect to periprosthetic osteoclastogenesis. THP-1 monocytic cells were differentiated to macrophage-like cells and exposed to LPS-detoxified polyethylene and prosthesis-derived TiAlV-particles. TNF, release was analyzed in culture supernatant by ELISA. NF-kB activation was examined by electrophoretic mobility shift assay (EMSA), and NF-kB target promoter activities including transactivation of the TNF, promoter were determined by luciferase reporter gene assays. Differentiated THP-1 macrophages were exposed to increasing numbers of particles for 0, 60, 180 and 360 min. Both, polyethylene- and TiAlV-particles induced a significant activation of both NF-kB and TNF, promoters at 180 min. A significant TNF, release was detected after 360 min exposure to polyethylene- and TiAlV-particles in a dose dependent manner. In comparison, LPS induced a much greater activation of NF-kB and TNF, promoters, and TNF, secretion into the supernatant was strongly induced. These results provide evidence that induction of the NF-kB signal transduction pathway in macrophages plays a major role in initiating and mediating the inflammatory response leading to periprosthetic osteolysis. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] | ||||||||||