Peter, Katrin and Rehli, Michael and Singer, Katrin and Renner-Sattler, Kathrin and Kreutz, Marina (2015) Lactic acid delays the inflammatory response of human monocytes. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 457 (3). pp. 412-418. ISSN 0006-291X, 1090-2104
Full text not available from this repository. (Request a copy)Abstract
Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (ART) as well as the degradation of I kappa B alpha. Consistently, the LPS-induced nuclear accumulation of NF kappa B was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. (C) 2015 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MACROPHAGE DIFFERENTIATION; CELLS; EXPRESSION; GENE; PROLIFERATION; TRANSCRIPTION; GLYCOLYSIS; MOLECULES; INHIBIT; LACTATE; Tumor; Metabolism; Lactic acid; Monocyte; Inflammation; Signal transduction |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Jul 2019 06:10 |
| Last Modified: | 26 Jul 2019 06:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5962 |
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