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NFKB1 Glucocorticoid receptor Transcription factor AP-1 Glucocorticoid receptor Prostaglandin G/H synthase 2 Annexin A1 Cytosolic phospholipase A2 Annexin A1 Prostaglandin G/H synthase 1 Prostaglandin G/H synthase 2 Prostaglandin G/H synthase 1 Prostaglandin G/H synthase 2 Thromboxane-A synthase Prostacyclin synthase Prostaglandin E synthase Prostaglandin- H2 D-isomerase Aldo-keto reductase family 1 member C3 Aldo-keto reductase family 1 member C3 Carbonyl reductase [NADPH] 1 Glucocorticoid receptor Glucocorticoid receptor Glucocorticoid receptor Heat shock protein HSP 90-alpha Heat shock 70 kDa protein 1A/1B Peptidyl-prolyl cis-trans isomerase FKBP4 Peptidyl-prolyl cis-trans isomerase FKBP4 Heat shock protein HSP 90-alpha Heat shock 70 kDa protein 1A/1B Arachidonic acid Rimexolone Rimexolone O2 Prostaglandin G2 Prostaglandin H2 H2O Thromboxane A2 Prostaglandin I2 Prostaglandin E2 Prostaglandin D2 NADPH 11-Epi-PGF2a NADP Prostaglandin F2a NADPH NADP PC(18:0/20:4(5Z,8Z,11Z,14Z)) H2O LysoPC(18:0/0:0) Rimexolone Rimexolone Heme Heme Glutathione Rimexolone Rimexolone Acceptor Reduced acceptor Activator Protein 1 NF-kB C/EBP Prostaglandin Synthase G/H 2 Promoter Annexin-1 Linoleic Acid Metabolism Eicosanoids Calcium Heme Heme Heme Heme Glucocorticoid receptor-rimexolone complex binds to the promoter for Annexin-1 (A1) and upregulates the transcription of it. Glucocorticoid receptor-rimexolone complex inhibits transcription factors NF-kB and Activator Protein 1 (AP-1) from synthesizing prostaglandin G/H synthase 2 (COX-2). Lower concentrations of prostaglanding I2 reduces vasodilation so the swelling of inflammation decreases. Prostaglandin I2 is apart of the hyperalgesia response so it's decrease results in a reduced pain sensitivity. Lower concentrations of prostaglandin D2 decreases the activity of platelet aggregation as well as reducing vasodilation Nucleus Lower concentrations of prostaglandin E2 have similar effects fo PGI2 as it's reduction decreases vasodilation and pain sensitivity. Lower concentrations of prostagladin F2a decreases the amount of bronchoconstriction allowing air to flow more easily. Rimexolone readily crosses the cell membrane since they are highly lipophillic. Cytosol Phospholipase A2 is inhibited by Annexin-1 as it binds to the Ca2+ which is needed by phospholipase A2 to function. This inhibition reduces the amount of arachidonic acid that is cleaved from phospholipids. Lower concentrations of prostaglandin G/H synthase 2 result in the synthesis of prostaglandin G2 and H2 to be reduced. The reduction lowers the amount of prostanoids being produced which have varying effects on decreasing inflammation and immune response. As rimexolone binds to the glucocorticoid receptor, the chaperone proteins fall off. Glucocorticoid receptor-rimexolone complex translocates into the nucleus. Thromboxane A2 is responsible for activation of new platelets as well as platelet aggravation. Decreased levels of thromboxane A2 will decrease levels of platelet activity. Endoplasmic Reticulum Prostaglandin G/H Synthase 2 exits the nucleus through nuclear pores into the cell cytosol. Uvea Cell
Endoplasmic Reticulum Nucleus NFKB1 Unknown JUN Unknown PTGS2 ANXA1 PLA2G4A ANXA1 PTGS1 PTGS2 PTGS1 PTGS2 TBXAS1 PTGIS PTGES PTGDS AKR1C3 AKR1C3 CBR1 Unknown Unknown Unknown HSP90AA1 HSPA1A FKBP4 FKBP4 HSP90AA1 HSPA1A Arachidonic acid Rimexolone Rimexolone Oxygen Prostaglandin G2 Prostaglandin H2 Water Thromboxane A2 Prostaglandin I2 Prostaglandin E2 Prostaglandin D2 NADPH 11-Epi-PGF2a NADP Prostaglandin F2a NADPH NADP PC(18:0/20:4(5Z,8Z,11Z,14Z)) Water LysoPC(18:0/0:0) Rimexolone Rimexolone Rimexolone Rimexolone Acceptor Reduced acceptor Activator Protein 1 NF-kB C/EBP Prostaglandin Synthase G/H 2 Promoter Annexin-1 Linoleic Acid Metabolism Eicosanoids
NFKB1 JUN PTGS2 ANXA1 PLA2G4A ANXA1 PTGS1 PTGS2 PTGS1 PTGS2 TBXAS1 PTGIS PTGES PTGDS AKR1C3 AKR1C3 CBR1 HSP90AA1 HSPA1A FKBP4 FKBP4 HSP90AA1 HSPA1A 20:4 Rimexol Rimexol O2 PGG2 PGH2 H2O ThrmbA2 PrstgI2 PGE2 ProglD2 NADPH EiPGF2a NADP PGF2a NADPH NADP Lecithi H2O LPC18:0 Rimexol Rimexol Heme Heme GSH Rimexol Rimexol Accepto RA AP-1 NF-kB C/EBP COX-2 P Annex-1 Li Ac M Eicos Ca2+ Heme Heme Heme Heme Glucocorticoid receptor-rimexolone complex binds to the promoter for Annexin-1 (A1) and upregulates the transcription of it. Glucocorticoid receptor-rimexolone complex inhibits transcription factors NF-kB and Activator Protein 1 (AP-1) from synthesizing prostaglandin G/H synthase 2 (COX-2). Lower concentrations of prostaglanding I2 reduces vasodilation so the swelling of inflammation decreases. Prostaglandin I2 is apart of the hyperalgesia response so it's decrease results in a reduced pain sensitivity. Lower concentrations of prostaglandin D2 decreases the activity of platelet aggregation as well as reducing vasodilation Nucleus Lower concentrations of prostaglandin E2 have similar effects fo PGI2 as it's reduction decreases vasodilation and pain sensitivity. Lower concentrations of prostagladin F2a decreases the amount of bronchoconstriction allowing air to flow more easily. Rimexolone readily crosses the cell membrane since they are highly lipophillic. Cytosol Phospholipase A2 is inhibited by Annexin-1 as it binds to the Ca2+ which is needed by phospholipase A2 to function. This inhibition reduces the amount of arachidonic acid that is cleaved from phospholipids. Lower concentrations of prostaglandin G/H synthase 2 result in the synthesis of prostaglandin G2 and H2 to be reduced. The reduction lowers the amount of prostanoids being produced which have varying effects on decreasing inflammation and immune response. As rimexolone binds to the glucocorticoid receptor, the chaperone proteins fall off. Glucocorticoid receptor-rimexolone complex translocates into the nucleus. Thromboxane A2 is responsible for activation of new platelets as well as platelet aggravation. Decreased levels of thromboxane A2 will decrease levels of platelet activity. Endoplasmic Reticulum Prostaglandin G/H Synthase 2 exits the nucleus through nuclear pores into the cell cytosol. Uvea Cell
Endoplasmic Reticulum Nucleus NFKB1 JUN PTGS2 ANXA1 PLA2G4A ANXA1 PTGS1 PTGS2 PTGS1 PTGS2 TBXAS1 PTGIS PTGES PTGDS AKR1C3 AKR1C3 CBR1 HSP90AA1 HSPA1A FKBP4 FKBP4 HSP90AA1 HSPA1A 20:4 Rimexol Rimexol O2 PGG2 PGH2 H2O ThrmbA2 PrstgI2 PGE2 ProglD2 NADPH EiPGF2a NADP PGF2a NADPH NADP Lecithi H2O LPC18:0 Rimexol Rimexol Rimexol Rimexol Accepto RA AP-1 NF-kB C/EBP COX-2 P Annex-1 Li Ac M Eicos