Prostaglandin signaling (WP5088)

Homo sapiens

Authors

Aria Jadhav , Marvin Martens , Eric Weitz , and Egon Willighagen

Activity

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Cited In

• Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor (2022).
• Investigating Transcriptional Age Acceleration in Inflammatory Skin Diseases.
• Central nervous system and systemic inflammatory networks associated with acute neurological outcomes in COVID-19 (2025).
• Glypican-3 regulated epithelial mesenchymal transformation-related genes in osteosarcoma: based on comprehensive tumor microenvironment profiling (2025).

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Organisms

Homo sapiens

Communities

ONTOX

Annotations

Pathway Ontology

prostaglandin I2 signaling pathway prostaglandin E2 signaling pathway

Cell Type Ontology

macrophage fibroblast plasmacytoid dendritic cell T-helper 17 cell natural killer cell monocyte

Disease Ontology

COVID-19

References

1. Regulation by PGE2 of the production of interleukin-6, macrophage colony stimulating factor, and vascular endothelial growth factor in human synovial fibroblasts. Inoue H, Takamori M, Shimoyama Y, Ishibashi H, Yamamoto S, Koshihara Y. Br J Pharmacol. 2002 May;136(2):287–95. PubMed Europe PMC Scholia
2. Signaling through the prostaglandin I2 receptor IP protects against respiratory syncytial virus-induced illness. Hashimoto K, Graham BS, Geraci MW, FitzGerald GA, Egan K, Zhou W, et al. J Virol. 2004 Oct;78(19):10303–9. PubMed Europe PMC Scholia
3. Prostaglandin E2 induces the expression of functional inhibitory CD94/NKG2A receptors in human CD8+ T lymphocytes by a cAMP-dependent protein kinase A type I pathway. Zeddou M, Greimers R, de Valensart N, Nayjib B, Tasken K, Boniver J, et al. Biochem Pharmacol. 2005 Sep 1;70(5):714–24. PubMed Europe PMC Scholia
4. Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis. Honda T, Segi-Nishida E, Miyachi Y, Narumiya S. J Exp Med. 2006 Feb 20;203(2):325–35. PubMed Europe PMC Scholia
5. Peptidoglycan-induced IL-6 production in RAW 264.7 macrophages is mediated by cyclooxygenase-2, PGE2/PGE4 receptors, protein kinase A, I kappa B kinase, and NF-kappa B. Chen BC, Liao CC, Hsu MJ, Liao YT, Lin CC, Sheu JR, et al. J Immunol. 2006 Jul 1;177(1):681–93. PubMed Europe PMC Scholia
6. Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling. Boniface K, Bak-Jensen KS, Li Y, Blumenschein WM, McGeachy MJ, McClanahan TK, et al. J Exp Med. 2009 Mar 16;206(3):535–48. PubMed Europe PMC Scholia
7. Prostaglandin E2 inhibits IFN-alpha secretion and Th1 costimulation by human plasmacytoid dendritic cells via E-prostanoid 2 and E-prostanoid 4 receptor engagement. Fabricius D, Neubauer M, Mandel B, Schütz C, Viardot A, Vollmer A, et al. J Immunol. 2010 Jan 15;184(2):677–84. PubMed Europe PMC Scholia
8. Prostaglandin I2-IP signaling promotes Th1 differentiation in a mouse model of contact hypersensitivity. Nakajima S, Honda T, Sakata D, Egawa G, Tanizaki H, Otsuka A, et al. J Immunol. 2010 May 15;184(10):5595–603. PubMed Europe PMC Scholia
9. Activation of the EP₄ prostanoid receptor induces prostaglandin E₂ and pro-inflammatory cytokine production in human airway epithelial cells. Li T, Qi J, Cowley EA. Pulm Pharmacol Ther. 2011 Feb;24(1):42–8. PubMed Europe PMC Scholia
10. Tumour-loaded α-type 1-polarized dendritic cells from patients with chronic lymphocytic leukaemia produce a superior NK-, NKT- and CD8+ T cell-attracting chemokine profile. Gustafsson K, Junevik K, Werlenius O, Holmgren S, Karlsson-Parra A, Andersson PO. Scand J Immunol. 2011 Sep;74(3):318–26. PubMed Europe PMC Scholia
11. Prostaglandin E(2) (PGE (2)) suppresses natural killer cell function primarily through the PGE(2) receptor EP4. Holt D, Ma X, Kundu N, Fulton A. Cancer Immunol Immunother. 2011 Nov;60(11):1577–86. PubMed Europe PMC Scholia
12. Inflammation-restraining effects of prostaglandin E2 on natural killer-dendritic cell (NK-DC) interaction are imprinted during DC maturation. Van Elssen CHMJ, Vanderlocht J, Oth T, Senden-Gijsbers BLMG, Germeraad WTV, Bos GMJ. Blood. 2011 Sep 1;118(9):2473–82. PubMed Europe PMC Scholia
13. Prostaglandin I2 signaling drives Th17 differentiation and exacerbates experimental autoimmune encephalomyelitis. Zhou W, Dowell DR, Huckabee MM, Newcomb DC, Boswell MG, Goleniewska K, et al. PLoS One. 2012;7(5):e33518. PubMed Europe PMC Scholia
14. Prostaglandin E₂ promotes Th1 differentiation via synergistic amplification of IL-12 signalling by cAMP and PI3-kinase. Yao C, Hirata T, Soontrapa K, Ma X, Takemori H, Narumiya S. Nat Commun. 2013;4:1685. PubMed Europe PMC Scholia
15. Synovial fibroblasts directly induce Th17 pathogenicity via the cyclooxygenase/prostaglandin E2 pathway, independent of IL-23. Paulissen SMJ, van Hamburg JP, Davelaar N, Asmawidjaja PS, Hazes JMW, Lubberts E. J Immunol. 2013 Aug 1;191(3):1364–72. PubMed Europe PMC Scholia
16. IL-6-mediated induction of matrix metalloproteinase-9 is modulated by JAK-dependent IL-10 expression in macrophages. Kothari P, Pestana R, Mesraoua R, Elchaki R, Khan KMF, Dannenberg AJ, et al. J Immunol. 2014 Jan 1;192(1):349–57. PubMed Europe PMC Scholia
17. Prostaglandin E2 Induces IL-6 and IL-8 Production by the EP Receptors/Akt/NF-κB Pathways in Nasal Polyp-Derived Fibroblasts. Cho JS, Han IH, Lee HR, Lee HM. Allergy Asthma Immunol Res. 2014 Sep;6(5):449–57. PubMed Europe PMC Scholia
18. Prostaglandin E2 inhibits neutrophil extracellular trap formation through production of cyclic AMP. Shishikura K, Horiuchi T, Sakata N, Trinh DA, Shirakawa R, Kimura T, et al. Br J Pharmacol. 2016 Jan;173(2):319–31. PubMed Europe PMC Scholia
19. Macrophages in Tissue Repair, Regeneration, and Fibrosis. Wynn TA, Vannella KM. Immunity. 2016 Mar 15;44(3):450–62. PubMed Europe PMC Scholia
20. The Induction of Pro-IL-1β by Lipopolysaccharide Requires Endogenous Prostaglandin E2 Production. Zasłona Z, Pålsson-McDermott EM, Menon D, Haneklaus M, Flis E, Prendeville H, et al. J Immunol. 2017 May 1;198(9):3558–64. PubMed Europe PMC Scholia
21. Prostaglandin E2 stimulates adaptive IL-22 production and promotes allergic contact dermatitis. Robb CT, McSorley HJ, Lee J, Aoki T, Yu C, Crittenden S, et al. J Allergy Clin Immunol. 2018 Jan;141(1):152–62. PubMed Europe PMC Scholia
22. Prostaglandin I2 suppresses the development of diet-induced nonalcoholic steatohepatitis in mice. Kumei S, Yuhki KI, Kojima F, Kashiwagi H, Imamichi Y, Okumura T, et al. FASEB J. 2018 May;32(5):2354–65. PubMed Europe PMC Scholia
23. T cell-intrinsic prostaglandin E2-EP2/EP4 signaling is critical in pathogenic TH17 cell-driven inflammation. Lee J, Aoki T, Thumkeo D, Siriwach R, Yao C, Narumiya S. J Allergy Clin Immunol. 2019 Feb;143(2):631–43. PubMed Europe PMC Scholia
24. Prostaglandin-cytokine crosstalk in chronic inflammation. Yao C, Narumiya S. Br J Pharmacol. 2019 Feb;176(3):337–54. PubMed Europe PMC Scholia
25. Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC. Siu KL, Yuen KS, Castaño-Rodriguez C, Ye ZW, Yeung ML, Fung SY, et al. FASEB J. 2019 Aug;33(8):8865–77. PubMed Europe PMC Scholia
26. COVID-19: consider cytokine storm syndromes and immunosuppression. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. Lancet. 2020 Mar 28;395(10229):1033–4. PubMed Europe PMC Scholia
27. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Xiong Y, Liu Y, Cao L, Wang D, Guo M, Jiang A, et al. Emerg Microbes Infect. 2020 Dec;9(1):761–70. PubMed Europe PMC Scholia
28. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Liao M, Liu Y, Yuan J, Wen Y, Xu G, Zhao J, et al. Nat Med. 2020 Jun;26(6):842–4. PubMed Europe PMC Scholia
29. Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients. Zhou Z, Ren L, Zhang L, Zhong J, Xiao Y, Jia Z, et al. Cell Host Microbe. 2020 Jun 10;27(6):883-890.e2. PubMed Europe PMC Scholia
30. Non-steroidal anti-inflammatory drugs, prostaglandins, and COVID-19. Robb CT, Goepp M, Rossi AG, Yao C. Br J Pharmacol. 2020 Nov;177(21):4899–920. PubMed Europe PMC Scholia