PMID- 28724635 OWN - NLM STAT- MEDLINE DCOM- 20170929 LR - 20240214 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 292 IP - 36 DP - 2017 Sep 8 TI - Heterodimers of the transcriptional factors NFATc3 and FosB mediate tissue factor expression for 15(S)-hydroxyeicosatetraenoic acid-induced monocyte trafficking. PG - 14885-14901 LID - 10.1074/jbc.M117.804344 [doi] AB - Tissue factor (TF) is expressed in vascular and nonvascular tissues and functions in several pathways, including embryonic development, inflammation, and cell migration. Many risk factors for atherosclerosis, including hypertension, diabetes, obesity, and smoking, increase TF expression. To better understand the TF-related mechanisms in atherosclerosis, here we investigated the role of 12/15-lipoxygenase (12/15-LOX) in TF expression. 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), the major product of human 15-LOXs 1 and 2, induced TF expression and activity in a time-dependent manner in the human monocytic cell line THP1. Moreover, TF suppression with neutralizing antibodies blocked 15(S)-HETE-induced monocyte migration. We also found that NADPH- and xanthine oxidase-dependent reactive oxygen species (ROS) production, calcium/calmodulin-dependent protein kinase IV (CaMKIV) activation, and interactions between nuclear factor of activated T cells 3 (NFATc3) and FosB proto-oncogene, AP-1 transcription factor subunit (FosB) are involved in 15(S)-HETE-induced TF expression. Interestingly, NFATc3 first induced the expression of its interaction partner FosB before forming the heterodimeric NFATc3-FosB transcription factor complex, which bound the proximal AP-1 site in the TF gene promoter and activated TF expression. We also observed that macrophages from 12/15-LOX(-/-) mice exhibit diminished migratory response to monocyte chemotactic protein 1 (MCP-1) and lipopolysaccharide compared with WT mouse macrophages. Similarly, compared with WT macrophages, monocytes from 12/15-LOX(-/-) mice displayed diminished trafficking, which was rescued by prior treatment with 12(S)-HETE, in a peritonitis model. These observations indicate that 15(S)-HETE-induced monocyte/macrophage migration and trafficking require ROS-mediated CaMKIV activation leading to formation of NFATc3 and FosB heterodimer, which binds and activates the TF promoter. CI - (c) 2017 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Kotla, Sivareddy AU - Kotla S AD - From the Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163 and. FAU - Singh, Nikhlesh K AU - Singh NK AD - From the Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163 and. FAU - Kirchhofer, Daniel AU - Kirchhofer D AD - Department of Early Discovery Biochemistry, Genentech Inc., South San Francisco, California 94080. FAU - Rao, Gadiparthi N AU - Rao GN AD - From the Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163 and. LA - eng GR - R01 HL064165/HL/NHLBI NIH HHS/United States GR - R01 HL103575/HL/NHLBI NIH HHS/United States PT - Journal Article DEP - 20170719 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (12-15-lipoxygenase) RN - 0 (FOSB protein, human) RN - 0 (Hydroxyeicosatetraenoic Acids) RN - 0 (MAS1 protein, human) RN - 0 (NFATC Transcription Factors) RN - 0 (NFATC3 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (Reactive Oxygen Species) RN - 9035-58-9 (Thromboplastin) RN - EC 1.13.11.31 (Arachidonate 12-Lipoxygenase) RN - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase) SB - IM EIN - J Biol Chem. 2022 Apr;298(4):101812. PMID: 35303608 MH - Animals MH - Arachidonate 12-Lipoxygenase/deficiency/genetics/*metabolism MH - Arachidonate 15-Lipoxygenase/deficiency/genetics/*metabolism MH - Cell Movement/*drug effects MH - Cells, Cultured MH - Humans MH - Hydroxyeicosatetraenoic Acids/*pharmacology MH - Macrophages/drug effects/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Monocytes/cytology/*drug effects/metabolism MH - NFATC Transcription Factors/*metabolism MH - Proto-Oncogene Mas MH - Proto-Oncogene Proteins c-fos/*metabolism MH - Reactive Oxygen Species/metabolism MH - Thromboplastin/*genetics/metabolism MH - Time Factors PMC - PMC5592668 OTO - NOTNLM OT - gene expression OT - migration OT - monocyte OT - signal transduction OT - trafficking COIS- The authors declare that they have no conflicts of interest with the contents of this article EDAT- 2017/07/21 06:00 MHDA- 2017/09/30 06:00 PMCR- 2018/09/08 CRDT- 2017/07/21 06:00 PHST- 2017/06/26 00:00 [received] PHST- 2017/07/14 00:00 [revised] PHST- 2017/07/21 06:00 [pubmed] PHST- 2017/09/30 06:00 [medline] PHST- 2017/07/21 06:00 [entrez] PHST- 2018/09/08 00:00 [pmc-release] AID - S0021-9258(20)34312-X [pii] AID - M117.804344 [pii] AID - 10.1074/jbc.M117.804344 [doi] PST - ppublish SO - J Biol Chem. 2017 Sep 8;292(36):14885-14901. doi: 10.1074/jbc.M117.804344. Epub 2017 Jul 19.