Prostaglandin signaling (Homo sapiens)

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15721193162312513232714, 18FibroblastsLegendNK cellsGene/ProteinProtection against viral infectionDecreased recruitment of CCR2 expressing monocytes and macrophagesDecreased platelet activationHuman plasmacytoid dendritic cellspro-IL1BcAMPIRF7Ca2+ effluxProstaglandin E2 receptorProstaglandin E2Prostaglandin E receptor 4IFNA1VEGFAIL6Prostaglandin E receptor 4CSF1COX2Prostaglandin E2MMP9IL17AIL6IL8IL1BTh17 cellsProstaglandin E2 receptorCCL2CXCL1MacrophageAREGVEGFATGFB1M2 MacrophageTissue repair, potential lung fibrosisProstaglandin E2 receptorProstaglandin E receptor 4NET formationProstaglandin E2 receptorProstaglandin E receptor 4PKAT cell activation and proliferationTh17 cellsIL17AIL17FAHR Inflammatory Th17 cell expansion22IFNGIL12AProstaglandin E receptor 4Natural killer cells antigen CD94NK and CD8+ T cell cytolytic activity6, 20CXCL9CXCL10NK cell migration28261617, 29cAMPcAMPNFKB1Cytokine storm, hyperinflammation (postive feedback loop)IL1BProstaglandin I2IFNA1IL1BIL6TNF5TNFCCL24Th17 cells11Th1 cellsIL17AIFNGIP-activated cAMP12IFN signalingProstaglandin E synthaseCOX2Prostaglandin E2IL6IL8TNFIL1ACCL2CXCL10CCL3IL1BNF-kB signalingEpithelial cells, monocytes, and macrophages10FibroblastsProstaglandin E receptor 4Prostaglandin E2 receptor9, 24, 308IL6 signalingASCNLRP3pro-CASP1Macrophages and monocytesInflammasome activationCCR2Monocytes and neutrophilsMonocyte and macrophage functionsNeutrophil extracellular trap (NET) releasePI3K3CD28T cell function22Myeloid cellsNK cell functionsT cell responsesCASP1MetaboliteComplexActivationStimulationConversionInhibitionIL6IL8Monocytes, macrophages, fibroblasts, airway epithelial cells


Description

Prostaglandins are among the many inflammatory mediators that incite a cytokine storm in COVID-19 after bradykinin receptor B1 (BDKRB1) activation. This pathway mainly focuses on PGE2 and PGI2 and their interactions that lead to hyperinflammation via cytokine storms, immunothrombosis, and recruitment of fibrosis-mediating factors (VEGF, TGFB1, AREG). These pathways take place in multiple cell types, e.g. monocytes, macrophages, fibroblasts, Th17 cells, and Nk cells.

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Bibliography

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  13. Kumei S, Yuhki KI, Kojima F, Kashiwagi H, Imamichi Y, Okumura T, Narumiya S, Ushikubi F; ''Prostaglandin I2suppresses the development of diet-induced nonalcoholic steatohepatitis in mice.''; FASEB J, 2018 PubMed Europe PMC Scholia
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  23. Robb CT, McSorley HJ, Lee J, Aoki T, Yu C, Crittenden S, Astier A, Felton JM, Parkinson N, Ayele A, Breyer RM, Anderton SM, Narumiya S, Rossi AG, Howie SE, Guttman-Yassky E, Weller RB, Yao C; ''Prostaglandin E2stimulates adaptive IL-22 production and promotes allergic contact dermatitis.''; J Allergy Clin Immunol, 2018 PubMed Europe PMC Scholia
  24. Chen BC, Liao CC, Hsu MJ, Liao YT, Lin CC, Sheu JR, Lin CH; ''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.''; J Immunol, 2006 PubMed Europe PMC Scholia
  25. Siu KL, Yuen KS, Castaño-Rodriguez C, Ye ZW, Yeung ML, Fung SY, Yuan S, Chan CP, Yuen KY, Enjuanes L, Jin DY; ''Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC.''; FASEB J, 2019 PubMed Europe PMC Scholia
  26. Gustafsson K, Junevik K, Werlenius O, Holmgren S, Karlsson-Parra A, Andersson PO; ''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.''; Scand J Immunol, 2011 PubMed Europe PMC Scholia
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History

View all...
CompareRevisionActionTimeUserComment
128022view16:11, 21 January 2024EweitzOntology Term : 'plasmacytoid dendritic cell' added !
128021view16:10, 21 January 2024EweitzOntology Term : 'natural killer cell' added !
128020view16:10, 21 January 2024EweitzOntology Term : 'T-helper 17 cell' added !
128019view16:10, 21 January 2024EweitzOntology Term : 'fibroblast' added !
128018view16:09, 21 January 2024EweitzOntology Term : 'macrophage' added !
128017view16:09, 21 January 2024EweitzOntology Term : 'monocyte' added !
127698view00:21, 23 November 2023EweitzFurther optimize layout of components
127697view23:03, 22 November 2023EweitzTrim more empty space, further standardize font size, etc.
127696view21:52, 22 November 2023EweitzCenter-align components
127695view21:46, 22 November 2023EweitzOptimize component offsets
127692view20:59, 22 November 2023EweitzShift diagram left, to trim excess negative space
127690view13:11, 22 November 2023EweitzOptimize layout in T cell function component
127689view12:58, 22 November 2023EweitzOptimize layout in NK cell functions component
127688view12:47, 22 November 2023EweitzOptimize layout in NF-kB signaling component
127687view12:30, 22 November 2023EweitzStandardize case
127685view12:20, 22 November 2023EweitzModified description
119639view06:34, 27 July 2021EgonwNot a conversion
119319view13:32, 23 June 2021AriajadhavUpdated and restructured pathway. Added legend
119018view19:19, 9 June 2021EgonwNot a human gene id
118971view12:33, 5 June 2021EgonwNot a human gene ID
117086view20:38, 16 May 2021AriajadhavMade the pathway compact
116865view14:51, 14 May 2021AriajadhavConnected lines
116773view00:28, 14 May 2021AriajadhavUpdated pathway, added references
116698view18:38, 9 May 2021AriajadhavModified description
116418view09:09, 7 May 2021EweitzModified title
116320view11:27, 30 April 2021Marvin M2Ontology Term : 'prostaglandin I2 signaling pathway' added !
116319view11:25, 30 April 2021Marvin M2Ontology Term : 'prostaglandin E2 signaling pathway' added !
116318view11:25, 30 April 2021Marvin M2Ontology Term : 'COVID-19' added !
116317view11:23, 30 April 2021Marvin M2connected lines
116312view15:10, 29 April 2021AriajadhavNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AHR ProteinENSG00000106546 (Ensembl)
AREGGeneProductENSG00000109321 (Ensembl)
ASCGeneProductENSG00000103490 (Ensembl)
CASP1GeneProductENSG00000137752 (Ensembl)
CCL2GeneProductENSG00000108691 (Ensembl)
CCL3GeneProductENSG00000277632 (Ensembl)
CCR2GeneProductENSG00000121807 (Ensembl)
CD28GeneProductENSG00000178562 (Ensembl)
COX2GeneProduct
CSF1GeneProductENSG00000184371 (Ensembl)
CXCL10GeneProductENSG00000169245 (Ensembl)
CXCL1GeneProductENSG00000163739 (Ensembl)
CXCL9GeneProductENSG00000138755 (Ensembl)
Ca2+ effluxMetaboliteCHEBI:29108 (ChEBI)
IFNA1GeneProductENSG00000197919 (Ensembl)
IFNGProteinIFNG (HGNC)
IL12AGeneProductENSG00000168811 (Ensembl)
IL17AGeneProductENSG00000112115 (Ensembl)
IL17FGeneProductENSG00000112116 (Ensembl)
IL1AGeneProductENSG00000115008 (Ensembl)
IL1BGeneProductENSG00000125538 (Ensembl)
IL6GeneProductENSG00000136244 (Ensembl)
IL8 GeneProductENSG00000169429 (Ensembl)
IP-activated cAMPMetaboliteHMDB0000058 (HMDB)
IRF7GeneProductENSG00000185507 (Ensembl)
MMP9GeneProductENSG00000100985 (Ensembl)
NFKB1GeneProductENSG00000109320 (Ensembl)
NLRP3GeneProductENSG00000162711 (Ensembl)
Natural killer cells antigen CD94ProteinE9PCX9 (Uniprot-TrEMBL)
PI3KGeneProductENSG00000105851 (Ensembl)
PKAProteinEC 2.7.11.11 (KEGG Genes)
Prostaglandin E receptor 4ProteinENSG00000171522 (Ensembl)
Prostaglandin E synthaseProteinO14684 (Uniprot-TrEMBL)
Prostaglandin E2 receptorProteinG3V2Y6 (Uniprot-TrEMBL)
Prostaglandin E2 receptorProteinP43116 (Uniprot-TrEMBL)
Prostaglandin E2Metabolite363-24-6 (CAS)
Prostaglandin I2Metabolite35121-78-9 (CAS)
TGFB1GeneProductTGFB1 (HGNC)
TNFGeneProductENSG00000232810 (Ensembl)
VEGFAGeneProductENSG00000112715 (Ensembl)
cAMPMetaboliteHMDB0000058 (HMDB)
pro-CASP1GeneProductENSG00000137752 (Ensembl)
pro-IL1BGeneProductENSG00000125538 (Ensembl)

Annotated Interactions

No annotated interactions

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