Glycolysis and the Pentose Phosphate Pathway Promote LPS-Induced NOX2 Oxidase- and IFN-β-Dependent Inflammation in Macrophages
Macrophages undergo a metabolic switch from oxidative phosphorylation to glycolysis when exposed to gram-negative bacterial lipopolysaccharide (LPS), which modulates antibacterial host defence mechanisms. Here, we show that LPS treatment of macrophages increased the classical oxidative burst respons...
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2022-07-01T00:00:00Z.
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| LEADER | 00000 am a22000003u 4500 | ||
|---|---|---|---|
| 001 | doaj_83b0f2bd21c8471894b47e8cff871b29 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Jonathan R. Erlich |e author |
| 700 | 1 | 0 | |a Eunice E. To |e author |
| 700 | 1 | 0 | |a Raymond Luong |e author |
| 700 | 1 | 0 | |a Felicia Liong |e author |
| 700 | 1 | 0 | |a Stella Liong |e author |
| 700 | 1 | 0 | |a Osezua Oseghale |e author |
| 700 | 1 | 0 | |a Mark A. Miles |e author |
| 700 | 1 | 0 | |a Steven Bozinovski |e author |
| 700 | 1 | 0 | |a Robert D. Brooks |e author |
| 700 | 1 | 0 | |a Ross Vlahos |e author |
| 700 | 1 | 0 | |a Stanley Chan |e author |
| 700 | 1 | 0 | |a John J. O'Leary |e author |
| 700 | 1 | 0 | |a Doug A. Brooks |e author |
| 700 | 1 | 0 | |a Stavros Selemidis |e author |
| 245 | 0 | 0 | |a Glycolysis and the Pentose Phosphate Pathway Promote LPS-Induced NOX2 Oxidase- and IFN-β-Dependent Inflammation in Macrophages |
| 260 | |b MDPI AG, |c 2022-07-01T00:00:00Z. | ||
| 500 | |a 10.3390/antiox11081488 | ||
| 500 | |a 2076-3921 | ||
| 520 | |a Macrophages undergo a metabolic switch from oxidative phosphorylation to glycolysis when exposed to gram-negative bacterial lipopolysaccharide (LPS), which modulates antibacterial host defence mechanisms. Here, we show that LPS treatment of macrophages increased the classical oxidative burst response via the NADPH oxidase (NOX) 2 enzyme, which was blocked by 2-deoxyglucose (2-DG) inhibition of glycolysis. The inhibition of the pentose phosphate pathway with 6-aminonicotinamide (6-AN) also suppressed the LPS-induced increase in NOX2 activity and was associated with a significant reduction in the mRNA expression of NOX2 and its organizer protein p47phox. Notably, the LPS-dependent enhancement in NOX2 oxidase activity was independent of both succinate and mitochondrial reactive oxygen species (ROS) production. LPS also increased type I IFN-β expression, which was suppressed by 2-DG and 6-AN and, therefore, is dependent on glycolysis and the pentose phosphate pathway. The type I IFN-β response to LPS was also inhibited by apocynin pre-treatment, suggesting that NOX2-derived ROS promotes the TLR4-induced response to LPS. Moreover, recombinant IFN-β increased NOX2 oxidase-dependent ROS production, as well as NOX2 and p47phox expression. Our findings identify a previously undescribed molecular mechanism where both glycolysis and the pentose phosphate pathway are required to promote LPS-induced inflammation in macrophages. | ||
| 546 | |a EN | ||
| 690 | |a inflammation | ||
| 690 | |a macrophages | ||
| 690 | |a NADPH oxidase | ||
| 690 | |a NOX2 | ||
| 690 | |a LPS | ||
| 690 | |a glycolysis | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Antioxidants, Vol 11, Iss 8, p 1488 (2022) | |
| 787 | 0 | |n https://www.mdpi.com/2076-3921/11/8/1488 | |
| 787 | 0 | |n https://doaj.org/toc/2076-3921 | |
| 856 | 4 | 1 | |u https://doaj.org/article/83b0f2bd21c8471894b47e8cff871b29 |z Connect to this object online. |