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LPS induces inflammatory chemokines via TLR-4 signalling and enhances the Warburg Effect in THP-1 cells


Autoři: Philemon Ubanako aff001;  Ntombikayise Xelwa aff001;  Monde Ntwasa aff002
Působiště autorů: School of Molecular & Cell Biology, University of the Witwatersrand, Johannesburg, Republic of South Africa aff001;  Department of Life & Consumer Sciences, University of South Africa, Florida, Johannesburg, Republic of South Africa aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222614

Souhrn

The Warburg Effect has emerged as a potential drug target because, in some cancer cell lines, it is sufficient to subvert it in order to kill cancer cells. It has also been shown that the Warburg Effect occurs in innate immune cells upon infection. Innate immune cells play critical roles in the tumour microenvironment but the Warburg Effect is not fully understood in monocytes. Furthermore, it is important to understand the impact of infections on key players in the tumour microenvironment because inflammatory conditions often precede carcinogenesis and mutated oncogenes induce inflammation. We investigated the metabolic programme in the acute monocytic leukaemia cell line, THP-1 in the presence and absence of lipopolysaccharide, mimicking bacterial infections. We found that stimulation of THP-1 cells by LPS induces a subset of pro-inflammatory chemokines and enhances the Warburg Effect. Surprisingly, perturbation of the Warburg Effect in these cells does not lead to cell death in contrast to what was observed in non-myeloid cancer cell lines in a previous study. These findings indicate that the Warburg Effect and inflammation are activated by bacterial lipopolysaccharide and may have a profound influence on the microenvironment.

Klíčová slova:

Cell cycle and cell division – Cytokines – Chemokines – Monocytes – Pyruvate – Warburg effect – Cell metabolism – Polymyxins


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