{"id":5155,"date":"2026-08-23T21:12:08","date_gmt":"2026-08-23T21:12:08","guid":{"rendered":"https:\/\/pge2-hypothesis.com\/?page_id=5155"},"modified":"2026-08-26T05:50:48","modified_gmt":"2026-08-26T05:50:48","slug":"pge2-and-lc-mechanisms","status":"publish","type":"page","link":"https:\/\/pge2-hypothesis.com\/?page_id=5155","title":{"rendered":"PGE2 and LC Mechanisms"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-page\" data-elementor-id=\"5155\" class=\"elementor elementor-5155\">\n\t\t\t\t<div class=\"elementor-element elementor-element-7198573 e-flex e-con-boxed e-con e-parent\" data-id=\"7198573\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-3db12a8 elementor-widget elementor-widget-spacer\" data-id=\"3db12a8\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-fcf1dce elementor-widget elementor-widget-heading\" data-id=\"fcf1dce\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">PGE2 and LC Mechanisms<\/h2>\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-ea9083b e-flex e-con-boxed e-con e-parent\" data-id=\"ea9083b\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-bcf636f elementor-widget elementor-widget-text-editor\" data-id=\"bcf636f\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t\t\t\t\t\t<p><br \/>The following Long COVID mechanisms described in the literature\u00b9\u02d2\u00b2 have direct relationships with PGE2 activity. <br \/>Persistent PGE2 upregulation may promote:<\/p><ul><li><strong>viral persistence and reactivation<\/strong>\u00b3<\/li><li><strong>pro-inflammatory cytokines that stimulate PGE2 production<\/strong> (cytokine storms)\u2074\u207b\u2076<\/li><li><strong>autoantibodies and class switching<\/strong>\u2077\u207b\u2079, and <strong>autoimmunity<\/strong>\u00b9\u2070\u02d2\u00b9\u00b9<\/li><li><strong>thrombotic processes<\/strong>, via EP3\u00b9\u00b2 and via COX-2\u00b9\u00b3\/TXA2 production\u00b9\u2074<\/li><li><strong>microbiome disruption<\/strong>\u00b9\u2075\u207b\u00b9\u2077 and <strong>bacterial translocation<\/strong>\u00b9\u2078<\/li><li><strong>mitochondrial dysfunction<\/strong>\u00b9\u2079\u207b\u00b2\u00b9<\/li><li><strong>endothelial dysfunction<\/strong>\u00b2\u00b2\u02d2\u00b2\u00b3<\/li><li><strong>inhibition of serotonin production and secretion<\/strong>\u00b2\u2074\u02d2\u00b2\u2075<\/li><li><strong>autonomic nervous system dysfunction<\/strong>\u00b2\u2076\u207b\u00b2\u2078<\/li><\/ul><p>This broad involvement suggests that PGE2 may act upstream of multiple pathways contributing to the heterogeneous manifestations of Long COVID and proposedly related syndromes.<\/p><p>Referenties<\/p><p>1\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Peluso, M. J. &amp; Deeks, S. G. Mechanisms of long COVID and the path toward therapeutics.\u00a0<em>Cell<\/em>\u00a0<strong>187<\/strong>, 5500-5529 (2024).\u00a0<a href=\"https:\/\/doi.org\/10.1016\/j.cell.2024.07.054\">https:\/\/doi.org\/10.1016\/j.cell.2024.07.054<\/a><\/p><p>2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Saxena, A. &amp; Mautner, J. A Disease Hidden in Plain Sight: Pathways and Mechanisms of Neurological Complications of Post-acute Sequelae of COVID-19 (NC-PASC).\u00a0<em>Mol Neurobiol<\/em>\u00a0<strong>62<\/strong>, 2530-2547 (2025).\u00a0<a href=\"https:\/\/doi.org\/10.1007\/s12035-024-04421-z\">https:\/\/doi.org\/10.1007\/s12035-024-04421-z<\/a><\/p><p>3\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Sander, W. J., O&#8217;Neill, H. G. &amp; Pohl, C. H. Prostaglandin E2 As a Modulator of Viral Infections.\u00a0<em>Frontiers in Physiology<\/em>\u00a0<strong>8<\/strong>\u00a0(2017).\u00a0<a href=\"https:\/\/doi.org\/10.3389\/fphys.2017.00089\">https:\/\/doi.org\/10.3389\/fphys.2017.00089<\/a><\/p><p>4\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Williams, J. A. &amp; Shacter, E. Regulation of macrophage cytokine production by prostaglandin E2. Distinct roles of cyclooxygenase-1 and -2.\u00a0<em>J Biol Chem<\/em>\u00a0<strong>272<\/strong>, 25693-25699 (1997).\u00a0<a href=\"https:\/\/doi.org\/10.1074\/jbc.272.41.25693\">https:\/\/doi.org\/10.1074\/jbc.272.41.25693<\/a><\/p><p>5\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Arias-Negrete, S., Keller, K. &amp; Chadee, K. 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J.<em>\u00a0et al.<\/em>\u00a0Cytokine-induced Prostaglandin E2 Synthesis and Cyclooxygenase-2 Activity Are Regulated Both by a Nitric Oxide-dependent and -independent Mechanism in Rat Osteoblasts in Vitro *.\u00a0<em>Journal of Biological Chemistry<\/em>\u00a0<strong>274<\/strong>, 1776-1782 (1999).\u00a0<a href=\"https:\/\/doi.org\/https:\/doi.org\/10.1074\/jbc.274.3.1776\">https:\/\/doi.org\/https:\/\/doi.org\/10.1074\/jbc.274.3.1776<\/a><\/p><p>7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Ishihara, Y.<em>\u00a0et al.<\/em>\u00a0Regulation of Immunoglobulin G2 Production by Prostaglandin E&lt;sub&gt;2&lt;\/sub&gt; and Platelet-Activating Factor.\u00a0<em>Infection and Immunity<\/em>\u00a0<strong>68<\/strong>, 1563-1568 (2000).\u00a0<a href=\"https:\/\/doi.org\/doi:10.1128\/iai.68.3.1563-1568.2000\">https:\/\/doi.org\/doi:10.1128\/iai.68.3.1563-1568.2000<\/a><\/p><p>8\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Roper, R. 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The receptor EP3 to PGE2: A rational target to prevent atherothrombosis without inducing bleeding.\u00a0<em>Prostaglandins Other Lipid Mediat<\/em>\u00a0<strong>121<\/strong>, 4-16 (2015).\u00a0<a href=\"https:\/\/doi.org\/10.1016\/j.prostaglandins.2015.10.001\">https:\/\/doi.org\/10.1016\/j.prostaglandins.2015.10.001<\/a><\/p><p>13\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Nam, J., Kwon, B., Yoon, Y. &amp; Choe, J. PGE2 stimulates COX-2 expression via EP2\/4 receptors and acts in synergy with IL-1\u03b2 in human follicular dendritic cell-like cells.\u00a0<em>European Journal of Inflammation<\/em>\u00a0<strong>16<\/strong>, 2058739218796386 (2018).\u00a0<a href=\"https:\/\/doi.org\/10.1177\/2058739218796386\">https:\/\/doi.org\/10.1177\/2058739218796386<\/a><\/p><p>14\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Violi, F., Harenberg, J., Pignatelli, P. &amp; Cammisotto, V. COVID-19 and Long-COVID Thrombosis: From Clinical and Basic Science to Therapeutics.\u00a0<em>Thromb Haemost<\/em>\u00a0<strong>124<\/strong>, 286-296 (2024).\u00a0<a href=\"https:\/\/doi.org\/10.1055\/s-0043-1776713\">https:\/\/doi.org\/10.1055\/s-0043-1776713<\/a><\/p><p>15\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Crittenden, S.<em>\u00a0et al.<\/em>\u00a0Prostaglandin E(2) promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells.\u00a0<em>Sci Adv<\/em>\u00a0<strong>7<\/strong>\u00a0(2021).\u00a0<a href=\"https:\/\/doi.org\/10.1126\/sciadv.abd7954\">https:\/\/doi.org\/10.1126\/sciadv.abd7954<\/a><\/p><p>16\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Grabauskas, G.<em>\u00a0et al.<\/em>\u00a0Prostaglandin E(2), Produced by Mast Cells in Colon Tissues From Patients With Irritable Bowel Syndrome, Contributes to Visceral Hypersensitivity in Mice.\u00a0<em>Gastroenterology<\/em>\u00a0<strong>158<\/strong>, 2195-2207.e2196 (2020).\u00a0<a href=\"https:\/\/doi.org\/10.1053\/j.gastro.2020.02.022\">https:\/\/doi.org\/10.1053\/j.gastro.2020.02.022<\/a><\/p><p>17\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Gao, J., Xiong, T., Grabauskas, G. &amp; Owyang, C. Mucosal Serotonin Reuptake Transporter Expression in Irritable Bowel Syndrome Is Modulated by Gut Microbiota Via Mast Cell&amp;#x2013;Prostaglandin E2.\u00a0<em>Gastroenterology<\/em>\u00a0<strong>162<\/strong>, 1962-1974.e1966 (2022).\u00a0<a href=\"https:\/\/doi.org\/10.1053\/j.gastro.2022.02.016\">https:\/\/doi.org\/10.1053\/j.gastro.2022.02.016<\/a><\/p><p>18\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Choudhry, M. A.<em>\u00a0et al.<\/em>\u00a0PGE2 suppresses intestinal T cell function in thermal injury: a cause of enhanced bacterial translocation.\u00a0<em>Shock<\/em>\u00a0<strong>16<\/strong>, 183-188 (2001).\u00a0<a href=\"https:\/\/doi.org\/10.1097\/00024382-200116030-00003\">https:\/\/doi.org\/10.1097\/00024382-200116030-00003<\/a><\/p><p>19\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Bryson, T. D.<em>\u00a0et al.<\/em>\u00a0Prostaglandin E2 affects mitochondrial function in adult mouse cardiomyocytes and hearts.\u00a0<em>Prostaglandins Leukot Essent Fatty Acids<\/em>\u00a0<strong>201<\/strong>, 102614 (2024).\u00a0<a href=\"https:\/\/doi.org\/10.1016\/j.plefa.2024.102614\">https:\/\/doi.org\/10.1016\/j.plefa.2024.102614<\/a><\/p><p>20\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Morotti, M.<em>\u00a0et al.<\/em>\u00a0PGE(2) inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial\u00a0function.\u00a0<em>Nature<\/em>\u00a0<strong>629<\/strong>, 426-434 (2024).\u00a0<a href=\"https:\/\/doi.org\/10.1038\/s41586-024-07352-w\">https:\/\/doi.org\/10.1038\/s41586-024-07352-w<\/a><\/p><p>21\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Chen, J.<em>\u00a0et al.<\/em>\u00a0Age-induced prostaglandin E2 impairs mitochondrial fitness and increases mortality to influenza infection.\u00a0<em>Nature Communications<\/em>\u00a0<strong>13<\/strong>, 6759 (2022).\u00a0<a href=\"https:\/\/doi.org\/10.1038\/s41467-022-34593-y\">https:\/\/doi.org\/10.1038\/s41467-022-34593-y<\/a><\/p><p>22\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Yin, J.<em>\u00a0et al.<\/em>\u00a0COX-2 mediates PM2.5-induced apoptosis and inflammation in vascular endothelial cells.\u00a0<em>Am J Transl Res<\/em>\u00a0<strong>9<\/strong>, 3967-3976 (2017).<\/p><p>23\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Perrot, C. Y., Herrera, J. L., Fournier-Goss, A. E. &amp; Komatsu, M. Prostaglandin E2 breaks down pericyte-endothelial cell interaction via EP1 and EP4-dependent downregulation of pericyte N-cadherin, connexin-43, and R-Ras.\u00a0<em>Sci Rep<\/em>\u00a0<strong>10<\/strong>, 11186 (2020).\u00a0<a href=\"https:\/\/doi.org\/10.1038\/s41598-020-68019-w\">https:\/\/doi.org\/10.1038\/s41598-020-68019-w<\/a><\/p><p>24\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Singh, A. K.<em>\u00a0et al.<\/em>\u00a0Prostaglandin-mediated inhibition of serotonin signaling controls the affective component of inflammatory pain.\u00a0<em>J Clin Invest<\/em>\u00a0<strong>127<\/strong>, 1370-1374 (2017).\u00a0<a href=\"https:\/\/doi.org\/10.1172\/jci90678\">https:\/\/doi.org\/10.1172\/jci90678<\/a><\/p><p>25\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Nakamura, K., Li, Y. Q., Kaneko, T., Katoh, H. &amp; Negishi, M. Prostaglandin EP3 receptor protein in serotonin and catecholamine cell groups: a double immunofluorescence study in the rat brain.\u00a0<em>Neuroscience<\/em>\u00a0<strong>103<\/strong>, 763-775 (2001).\u00a0<a href=\"https:\/\/doi.org\/10.1016\/s0306-4522(01)00027-6\">https:\/\/doi.org\/10.1016\/s0306-4522(01)00027-6<\/a><\/p><p>26\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Spicuzza, L., Giembycz, M. A., Barnes, P. J. &amp; Belvisi, M. G. Prostaglandin E2 suppression of acetylcholine release from parasympathetic nerves innervating guinea-pig trachea by interacting with prostanoid receptors of the EP3-subtype.\u00a0<em>British Journal of Pharmacology<\/em>\u00a0<strong>123<\/strong>, 1246-1252 (1998).\u00a0<a href=\"https:\/\/doi.org\/https:\/doi.org\/10.1038\/sj.bjp.0701720\">https:\/\/doi.org\/https:\/\/doi.org\/10.1038\/sj.bjp.0701720<\/a><\/p><p>27\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Zhang, Z. H.<em>\u00a0et al.<\/em>\u00a0EP\u2083 receptors mediate PGE\u2082-induced hypothalamic paraventricular nucleus excitation and sympathetic activation.\u00a0<em>Am J Physiol Heart Circ Physiol<\/em>\u00a0<strong>301<\/strong>, H1559-1569 (2011).\u00a0<a href=\"https:\/\/doi.org\/10.1152\/ajpheart.00262.2011\">https:\/\/doi.org\/10.1152\/ajpheart.00262.2011<\/a><\/p><p>28\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Ariumi, H.<em>\u00a0et al.<\/em>\u00a0Roles of the central prostaglandin EP3 receptors in cardiovascular regulation in rats.\u00a0<em>Neurosci Lett<\/em>\u00a0<strong>324<\/strong>, 61-64 (2002).\u00a0<a href=\"https:\/\/doi.org\/10.1016\/s0304-3940(02)00174-x\">https:\/\/doi.org\/10.1016\/s0304-3940(02)00174-x<\/a><\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>PGE2 and LC Mechanisms The following Long COVID mechanisms described in the literature\u00b9\u02d2\u00b2 have direct relationships with PGE2 activity. 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