Doerpinghaus, Michael and Brieger, Anne and Panichkina, Olga and Rink, Lothar and Haase, Hajo (2016) Lead ions abrogate lipopolysaccharide-induced nitric monoxide toxicity by reducing the expression of STAT1 and iNOS. JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, 37. pp. 117-124. ISSN 0946-672X,
Full text not available from this repository. (Request a copy)Abstract
Lead is a widespread environmental pollutant and the highly poisonous metal compromises multiple organs in the body. Among other tissues and cells, lead ions (Pb2+) can affect macrophages and microglia cells. The present study observed a concentration-dependent protection of BV-2 microglia and RAW 264.7 macrophages by Pb2+ against lipopolysaccharide (LPS)-induced toxicity. Both cell lines are potent producers of two substances that have previously been shown to mediate cytotoxic effects of LPS. These are the pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha and nitric monoxide (NO), which creates nitrosative stress, hampering the distribution of invading pathogens and tumor cells. While the expression of TNF-alpha. was unaffected by Pb2+, the production of NO was significantly inhibited. Moreover, blocking NO synthesis by low molecular weight inhibitors prevented LPS-mediated toxicity, confirming the role of NO in these events. Pb2+ exposure led to a downregulation of LPS-induced expression of the transcription factor STAT1, which is involved in iNOS transcription. Moreover, iNOS mRNA and protein levels were reduced in the presence of Pb2+, explaining the reduced formation of NO and a subsequent increase of cellular viability in vitro. In vivo, the effect might limit collateral damage caused by excessive NO production, but also impair the efficiency of NO as a central mediator of the defense against various pathogens. (C) 2016 Elsevier GmbH. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OXIDE SYNTHASE GENE; OXIDATIVE STRESS; MOUSE MACROPHAGES; IMMUNE FUNCTION; TNF-ALPHA; APOPTOSIS; EXPOSURE; CELLS; VITRO; MICE; Lead; LPS toxicity; Macrophages; Nitric monoxide; TNF; Microglia |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Dec 2019 11:53 |
| Last Modified: | 13 Dec 2019 11:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2658 |
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