PMID- 30894323 OWN - NLM STAT- MEDLINE DCOM- 20200521 LR - 20200521 IS - 1873-4596 (Electronic) IS - 0891-5849 (Linking) VI - 135 DP - 2019 May 1 TI - Differential induction of nuclear factor-like 2 signature genes with toll-like receptor stimulation. PG - 245-250 LID - S0891-5849(18)32341-4 [pii] LID - 10.1016/j.freeradbiomed.2019.03.018 [doi] AB - Inflammation is associated with production of reactive oxygen species (ROS) and results in the induction of thioredoxin (TXN) and peroxiredoxins (PRDXs) and activation of nuclear factor-like 2 (Nrf2). In this study we have used the mouse RAW 264.7 macrophage and the human THP-1 monocyte cell line to investigate the pattern of expression of three Nrf2 target genes, PRDX1, TXN reductase (TXNRD1) and heme oxygenase (HMOX1), by activation of different Toll-like receptors (TLRs). We found that, while the TLR4 agonist lipopolysaccharide (LPS) induces all three genes, the pattern of induction with agonists for TLR1/2, TLR3, TLR2/6 and TLR7/8 differs depending on the gene and the cell line. In all cases, the extent of induction was HMOX1>TXNRD1>PRDX1. Since LPS was a good inducer of all genes in both cell lines, we studied the mechanisms mediating LPS induction of the three genes using mouse RAW 264.7 cells. To assess the role of ROS we used the antioxidant N-acetylcysteine (NAC). Only LPS induction of HMOX1 was inhibited by NAC while that of TXNRD1 and PRDX1 was unaffected. These three genes were also induced by phorbol myristate acetate (PMA), a ROS-inducer acting by activation of protein kinase C (PKC). The protein kinase inhibitor staurosporine inhibited the induction of all three genes by PMA but only that of HMOX1 by LPS. This indicates that activation of these genes by inflammatory agents is regulated by different mechanisms involving either ROS or protein kinases, or both. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Ingram, Sonia AU - Ingram S AD - Brighton and Sussex Medical School, Falmer, BN1 9PS, United Kingdom. FAU - Mengozzi, Manuela AU - Mengozzi M AD - Brighton and Sussex Medical School, Falmer, BN1 9PS, United Kingdom. FAU - Sacre, Sandra AU - Sacre S AD - Brighton and Sussex Medical School, Falmer, BN1 9PS, United Kingdom. FAU - Mullen, Lisa AU - Mullen L AD - Brighton and Sussex Medical School, Falmer, BN1 9PS, United Kingdom. FAU - Ghezzi, Pietro AU - Ghezzi P AD - Brighton and Sussex Medical School, Falmer, BN1 9PS, United Kingdom. Electronic address: p.ghezzi@bsms.ac.uk. LA - eng PT - Journal Article DEP - 20190317 PL - United States TA - Free Radic Biol Med JT - Free radical biology & medicine JID - 8709159 RN - 0 (Lipopolysaccharides) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Proteins) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, mouse) RN - 0 (Reactive Oxygen Species) RN - 0 (TLR3 protein, mouse) RN - 0 (Tlr2 protein, mouse) RN - 0 (Tlr4 protein, mouse) RN - 0 (Tlr7 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 3) RN - 0 (Toll-Like Receptor 4) RN - 0 (Toll-Like Receptor 7) RN - EC 1.11.1.15 (Peroxiredoxins) RN - EC 1.11.1.15 (Prdx1 protein, mouse) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.14.14.18 (Hmox1 protein, mouse) RN - EC 1.8.1.9 (Thioredoxin Reductase 1) RN - EC 1.8.1.9 (Txnrd1 protein, mouse) RN - EC 2.7.11.13 (Protein Kinase C) RN - H88EPA0A3N (Staurosporine) SB - IM MH - Animals MH - Gene Expression Regulation/drug effects MH - Heme Oxygenase-1/genetics MH - Inflammation/*genetics/metabolism/pathology MH - Lipopolysaccharides/pharmacology MH - Membrane Glycoproteins/genetics MH - Membrane Proteins/genetics MH - Mice MH - NF-E2-Related Factor 2/*genetics MH - Peroxiredoxins/*genetics MH - Protein Kinase C/antagonists & inhibitors/genetics MH - RAW 264.7 Cells MH - Reactive Oxygen Species/metabolism MH - Staurosporine/pharmacology MH - Thioredoxin Reductase 1/*genetics MH - Toll-Like Receptor 2/genetics MH - Toll-Like Receptor 3/genetics MH - Toll-Like Receptor 4/genetics MH - Toll-Like Receptor 7/genetics OTO - NOTNLM OT - Antioxidant OT - Inflammation OT - Nrf2 OT - Peroxiredoxin OT - Thioredoxin OT - Toll-like receptors EDAT- 2019/03/22 06:00 MHDA- 2020/05/22 06:00 CRDT- 2019/03/22 06:00 PHST- 2018/10/26 00:00 [received] PHST- 2019/03/11 00:00 [revised] PHST- 2019/03/13 00:00 [accepted] PHST- 2019/03/22 06:00 [pubmed] PHST- 2020/05/22 06:00 [medline] PHST- 2019/03/22 06:00 [entrez] AID - S0891-5849(18)32341-4 [pii] AID - 10.1016/j.freeradbiomed.2019.03.018 [doi] PST - ppublish SO - Free Radic Biol Med. 2019 May 1;135:245-250. doi: 10.1016/j.freeradbiomed.2019.03.018. Epub 2019 Mar 17.