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LPS-induced Expression (LPS-induce + expression)
Selected AbstractsCactus-independent nuclear translocation of Drosophila RELISHJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2001William D. Cornwell Abstract Insects can effectively and rapidly clear microbial infections by a variety of innate immune responses including the production of antimicrobial peptides. Induction of these antimicrobial peptides in Drosophila has been well established to involve NF-,B elements. We present evidence here for a molecular mechanism of Lipopolysaccharide (LPS)-induced signaling involving Drosophila NF-,B, RELISH, in Drosophila S2 cells. We demonstrate that LPS induces a rapid processing event within the RELISH protein releasing the C-terminal ankyrin-repeats from the N-terminal Rel homology domain (RHD). Examination of the cellular localization of RELISH reveals that the timing of this processing coincides with the nuclear translocation of the RHD and the retention of the ankyrin-repeats within the cytoplasm. Both the processing and the nuclear translocation immediately precede the expression of antibacterial peptide genes cecropin A1, attacin, and diptericin. Over-expression of the RHD but not full-length RELISH results in an increase in the promoter activity of the cecropin A1 gene in the absence of LPS. Furthermore, the LPS-induced expression of these antibacterial peptides is greatly reduced when RELISH expression is depleted via RNA-mediated interference. In addition, loss of cactus expression via RNAi revealed that RELISH activation and nuclear translocation is not dependent on the presence of cactus. Taken together, these results suggest that this signaling mechanism involving the processing of RELISH followed by nuclear translocation of the RHD is central to the induction of at least part of the antimicrobial response in Drosophila, and is largely independent of cactus regulation. J. Cell. Biochem. 82: 22,37, 2001. © 2001 Wiley-Liss, Inc. [source] Melatonin inhibits lipopolysaccharide-induced CC chemokine subfamily gene expression in human peripheral blood mononuclear cells in a microarray analysisJOURNAL OF PINEAL RESEARCH, Issue 2 2007Hae Jeong Park Abstract:, Melatonin possesses a number of important biologic activities including oncostatic, anti-oxidant, and immunostimulatory actions. This study was designed to assess the effects of melatonin on inflammation-related gene expression in lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs), using CombiMatrix 2K Human Inflammation chip. After pretreatment with melatonin (100 ,m) for 4 hr, cells were incubated with LPS (1 ,g/mL) for 24 hr. We compared gene expression profiles between LPS-treated, melatonin-treated, LSP/melatonin-treated, and control groups. LPS induced the upregulation of 95 genes, compared with controls. Melatonin pretreatment in LPS-stimulated PBMCs suppressed the expression of 23 genes more than twofold. Interestingly, melatonin showed a suppressive effect on the expression of CC chemokine subfamily genes, including CCL2/MCP1, CCL3/MIP1,, CCL4/MIP1,, CCL5/RANTES, CCL8/MCP2, CCL20/MDC, and CCL22/MIP3,, in LPS-stimulated PBMCs. This result was confirmed by reverse transcriptase polymerase chain reaction. Among the CC chemokine subfamily genes, particularly, the expression of CCL2 and CCL5 was markedly downregulated by melatonin in LPS-stimulated PBMCs. The secretion levels of CCL2 and CCL5 were measured using enzyme-linked immunosorbent assay. Stimulation of PBMCs by LPS induced the secretion of CCL2 (2334.3 ± 161.4 pg/mL, mean ± S.E.M.), whereas melatonin pretreatment (153.0 ± 3.8 pg/mL) inhibited the LPS-induced secretion of CCL2. Melatonin pretreatment (2696.2 ± 385.3 pg/mL) also inhibited the LPS-induced secretion of CCL5 (4679.6 ± 107.5 pg/mL). Taken together, these results suggest that melatonin may have a suppressive effect on LPS-induced expression of CC chemokine genes, especially CCL2 and CCL5, which may explain its beneficial effects in the treatment of various inflammatory conditions. [source] Effects of statins on adhesion molecule expression in endothelial cellsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2003Y. Dimitrova Summary.,Background:,Inhibitors of HMG-CoA reductase are widely used to prevent atherosclerosis progression. The expression of adhesion molecules on activated endothelial cells (EC) is an important step in the initiation and progression of atherosclerosis. Objectives:,We investigated whether adhesion molecule expression on activated EC is influenced by simvastatin, fluvastatin and pravastatin and, if so, by which mechanisms. Methods:,Human EC from umbilical veins or saphenous veins were pretreated overnight with statins with or without mevalonate, and also for simvastatin or fluvastatin with the isoprenoid intermediates, farnesyl pyrophosphate (FPP), or geranylgeranyl pyrophosphate (GGPP). After 4,6 h activation with tumor necrosis factor (TNF)-, or lipopolysaccharide (LPS), surface adhesion molecule expression was evaluated by ELISA and by flow cytometry. The same experiments were performed with selective inhibitors of geranylgeranyltransferase (GGTI-286) and farnesyltransferase (FTI-277). Results:,Pretreatment with simvastatin, fluvastatin or pravastatin potentiated the TNF-, and LPS-induced expression of E-selectin and VCAM-1, and mevalonate reversed the potentiating effect of these statins. GGPP also reversed the potentiating effect of simvastatin or fluvastatin on adhesion molecule expression, while FPP only partially reversed this effect. Furthermore, GGTI-286, but not FTI-277, mimicked the effect of simvastatin by increasing the TNF-,-mediated overexpression of E-selectin. Conclusions:,Statins increase E-selectin- and VCAM-1-induced expression on vascular endothelial cells stimulated with TNF-, or LPS. The inhibition of geranylgeranylated proteins could contribute to this effect. [source] Selenium attenuates pro-inflammatory gene expression in macrophagesMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 11 2008Hema Vunta Abstract Selenium (Se) is an important element required for the optimal functioning of the immune system. Particularly in macrophages, which play a pivotal role in immune regulation, Se acts as a major antioxidant in the form of selenoproteins to mitigate the cytotoxic effects of reactive oxygen species. Here we describe the role of Se as an anti-inflammatory agent and its effect on the macrophage signal transduction pathways elicited by bacterial endotoxin, LPS. Our studies demonstrate that supplementation of Se to macrophages (Se-deficient) leads to a significant decrease in the LPS-induced expression of two important pro-inflammatory genes, cyclooxygenase-2 (COX-2) and tumor necrosis factor-, (TNF-,) via the inhibition of MAP kinase pathways. Furthermore, Se-deficiency in mice exacerbated the LPS-mediated infiltration of macrophages into the lungs suggesting that Se status is a crucial host factor that regulates inflammation. In summary, our results indicate that Se plays an important role as an anti-inflammatory agent by tightly regulating the expression of pro-inflammatory genes in immune cells. [source] ORIGINAL ARTICLE: TNF, Gene Silencing Reduced Lipopolysaccharide-Promoted Proliferation of Endometriotic Stromal CellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2009Ayako Miyamoto Problem, We previously reported that lipopolysaccharide (LPS)-promoted endometriotic stromal cell (ESC) proliferation by inducing TNF, production. The aim of this study was to investigate the efficacy of TNF, gene silencing on LPS-treated ESCs. Method of study, Endometriotic stromal cells (ESCs) and endometrial stromal cells (ESCs) (EMSCs) were obtained from ovarian chocolate cysts and uterine myoma, respectively. Using PCR array, LPS-induced gene expression profiling after transfection of TNF, siRNA into ESCs was performed. Down-regulated genes by TNF, silencing were examined using real-time RT-PCR. Effect of TNF, silencing was examined using ELISA and BrdU incorporation, respectively. Results, In PCR array, TNF, silencing in ESCs repressed LPS-induced expression of cIAP2 and IL-8, NF,B pathway responsive genes. After adding LPS, the levels of cIAP2 and IL-8 expression in ESCs were higher compared with those in EMSCs. TNF, silencing attenuated the LPS-induced ESC proliferation. Conclusion, Tumor necrosis factor , may be involved in cell proliferation of endometriotic tissues. [source] | |||||||||||||