IL-18 signaling pathway (WP4754)

Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and was initially described as an IFN-γ-inducing factor derived from anti-CD3-stimulated Th1 cells. IL-18 plays a significant role in the activation of hematopoietic cell types mediating both Th1 and Th2 responses and is the primary inducer of interferon-γ in these cells. The biological activity of IL-18 is mediated through its binding to the IL-18 receptor complex (IL-18R) and activation of nuclear factor-kB (NF-kB), culminating in the production and release of several cytokines, chemokines, and cellular adhesion molecules. In certain cell types, IL-18 also activates mitogen-activated protein kinases (MAPKs) and PI3K/AKT signaling modules leading to the production and release of proinflammatory cytokines. IL-18 mediated signaling acts as one of the vital components of the immunomodulatory cytokine networks involved in host defense, inflammation, and tissue regeneration.
last edited


Subbannayya, Khanspers, Egonw, and Rex D A B

Cited In


Homo sapiens



Pathway Ontology: interleukin-1 signaling pathway Interleukin mediated signaling pathway oxidative phosphorylation pathway signaling pathway in the adaptive immune response


Label Type Compact Identifier
IRAK1 Protein ncbigene:3654
CYCS GeneProduct ncbigene:54205
TRAF6 Protein ncbigene:7189
IL18RAP Protein ncbigene:8807
IL18 Protein ncbigene:3606
BAX GeneProduct ncbigene:581
IL18R1 Protein ncbigene:8809
MAPK1 GeneProduct ncbigene:5594
IL-18BP GeneProduct ncbiprotein:10068
CASP8 GeneProduct ncbigene:841
NOX1 GeneProduct ncbigene:27035
TICAM2 GeneProduct ncbigene:353376
SLC12A3 GeneProduct ncbigene:6559
LCK GeneProduct ncbigene:3932
CYCS GeneProduct ncbigene:54205
NFKB1 GeneProduct ncbigene:4790
NCF1 GeneProduct ncbigene:653361
NCF2 GeneProduct ncbigene:4688
NCF1 GeneProduct ncbigene:653361
NCF2 GeneProduct ncbigene:4688
IMP3 GeneProduct ncbigene:55272
ELAVL1 GeneProduct ncbigene:1994
CTNNB1 GeneProduct ncbigene:1499
GSK3B GeneProduct ncbigene:2932
CCL2 Rna ncbigene:6347
CCL3 Rna ncbigene:6348
CCL4 Rna ncbigene:6351
IL18R1 Rna ncbigene:8809
IL18RAP Rna ncbigene:8807
IL18BP Rna ncbigene:10068
IFNG Rna ncbigene:3458
MMP3 Rna ncbigene:4314
MMP8 Rna ncbigene:4317
MMP14 Rna ncbigene:4323
MMP13 Rna ncbigene:4322
MMP9 Rna ncbigene:4318
MMP2 Rna ncbigene:4313
LTB Rna ncbigene:4050
IL13 Rna ncbigene:3596
TIMP3 Rna ncbigene:7078
TIMP1 Rna ncbigene:7076
PTX3 Rna ncbigene:5806
IER3 Rna ncbigene:8870
TP53 Rna ncbigene:7157
MYH6 Rna ncbigene:4624
IL17RC Rna ncbigene:84818
IL18 Rna ncbigene:3606
TRPM7 Rna ncbigene:54822
DEK Rna ncbigene:7913
FOXN3 Rna ncbigene:1112
PRCC Rna ncbigene:5546
HSPB8 Rna ncbigene:26353
CCL5 Rna ncbigene:6352
BTG2 Rna ncbigene:7832
TNIP3 Rna ncbigene:79931
CCL1 Rna ncbigene:6346
TMEM165 Rna ncbigene:55858
BIN1 Rna ncbigene:274
TSHZ1 Rna ncbigene:10194
MBTPS1 Rna ncbigene:8720
PTPN7 Rna ncbigene:5778
PHF20 Rna ncbigene:51230
TRPC2 Rna ncbigene:7221
MTCH1 Rna ncbigene:23787
HPS1 Rna ncbigene:3257
SLC4A7 Rna ncbigene:9497
AARS Rna ncbigene:16
UCK1 Rna ncbigene:83549
ZNF219 Rna ncbigene:51222
NSMF Rna ncbigene:26012
KCNH2 Rna ncbigene:3757
PPP1R13L Rna ncbigene:10848
PLOD3 Rna ncbigene:8985
MEPCE Rna ncbigene:56257
ARFGAP2 Rna ncbigene:84364
RASA3 Rna ncbigene:22821
TRPC4AP Rna ncbigene:26133
PTMS Rna ncbigene:5763
EEF2 Rna ncbigene:1938
Protein GeneProduct ncbigene:11
TRAF1 Rna ncbigene:7185
FAS Rna ncbigene:355
FADD Rna ncbigene:8772
TNFSF11 Rna ncbigene:8600
TNFRSF11B Rna ncbigene:4982
TNFAIP2 Rna ncbigene:7127
TNFAIP3 Rna ncbigene:7128
TNF Rna ncbigene:7124
FASLG Rna ncbigene:356
CLDN12 Rna ncbigene:9069
CLDN4 Rna ncbigene:1364
CLDN3 Rna ncbigene:1365
CLDN1 Rna ncbigene:9076
CLDN15 Rna ncbigene:24146
JUN Rna ncbigene:3725
RUNX2 Rna ncbigene:860
FOS Rna ncbigene:2353
IRF6 Rna ncbigene:3664
KLF2 Rna ncbigene:10365
BIRC3 Rna ncbigene:330
BAD Rna ncbigene:572
BCL2 Rna ncbigene:596
BCL2L1 Rna ncbigene:598
PTEN Rna ncbigene:5728
PTPRZ1 Rna ncbigene:5803
CCNB2 Rna ncbigene:9133
CCNA2 Rna ncbigene:890
CDK5R2 Rna ncbigene:8941
PLA2G7 Rna ncbigene:7941
NACA Rna ncbigene:4666
EPB41 Rna ncbigene:2035
SYT10 Rna ncbigene:341359
ZNF444 Rna ncbigene:55311
RUSC1 Rna ncbigene:23623
CCDC9 Rna ncbigene:26093
FAM110A Rna ncbigene:83541
ITM2C Rna ncbigene:81618
GRN Rna ncbigene:2896
ATF3 Rna ncbigene:467
NFKBIA Rna ncbigene:4792
NFKBIE Rna ncbigene:4794
RELB Rna ncbigene:5966
NFKB2 Rna ncbigene:4791
REL Rna ncbigene:5966
NFKB1 Rna ncbigene:4790
RELA Rna ncbigene:5970
NFKBIZ Rna ncbigene:64332
AKT1 GeneProduct ncbiprotein:NP_005154.2
MAPK3 GeneProduct ncbigene:5595
CREB1 GeneProduct ncbiprotein:NP_604391.1
MAPK14 GeneProduct ncbiprotein:NP_001306.1
PIK3R1 GeneProduct ncbigene:5295
ELK1 GeneProduct ncbiprotein:NP_001107595.1
MAPK8 GeneProduct ncbiprotein:NP_620637.1
ATF2 Rna ncbigene:467
CHUK GeneProduct ncbigene:1147
IKBKB GeneProduct ncbigene:3551
RPS6 GeneProduct ncbiprotein:NP_001001.2
SRC GeneProduct ncbiprotein:NP_005408.1
NFKBIA GeneProduct ncbigene:4792
HSPB1 GeneProduct ncbigene:3315
CSN2 GeneProduct ncbigene:1447
MAP3K7 GeneProduct ncbigene:6885
GSK3A GeneProduct ncbiprotein:NP_002084.2
PTEN GeneProduct ncbigene:5728
ACACB GeneProduct ncbigene:32
JUN GeneProduct ncbiprotein:NP_002219.1
GRIN2B GeneProduct ncbigene:2904
PRKCA GeneProduct ncbigene:5578
PRKCB GeneProduct ncbigene:5579
RAF1 GeneProduct ncbiprotein:NP_001341618.1
TNFRSF1A GeneProduct ncbigene:7132
MEF2A GeneProduct ncbigene:4205
CEBPB GeneProduct ncbigene:1051
GATA1 GeneProduct ncbigene:2623
SP1 GeneProduct ncbigene:6667
CFLAR GeneProduct ncbigene:8837
BID GeneProduct ncbigene:637
CASP3 GeneProduct ncbigene:836
IRF1 GeneProduct ncbigene:3659
TNF GeneProduct ncbigene:7124
TP53 GeneProduct ncbigene:7157
FASLG GeneProduct ncbigene:356
FAS GeneProduct ncbigene:355
MAPK9 GeneProduct ncbigene:5601
Protein GeneProduct ncbigene:11
MYD88 Protein ncbigene:4615
IL1B Rna ncbigene:3553
IL2RA Rna ncbigene:3559
IL10 Rna ncbigene:3586
IL12B Rna ncbigene:3593
IL9 Rna ncbigene:3578
IL6 Rna ncbigene:3569
CCL19 Rna ncbigene:6363
CCL20 Rna ncbigene:6364
CXCL16 Rna ncbigene:58191
CXCL2 Rna ncbigene:2920
CXCL3 Rna ncbigene:2921
CCL18 Rna ncbigene:6362
CXCL8 Rna ncbigene:3576
MMP1 Rna ncbigene:4312
NR1H3 Rna ncbigene:10062
ABHD16A Rna ncbigene:7920
TACR1 Rna ncbigene:6869
SDC4 Rna ncbigene:6385
RGS16 Rna ncbigene:6004
SOCS3 Rna ncbigene:9021
EPS8 Rna ncbigene:2059
GRM7 Rna ncbigene:2917
NR4A1 Rna ncbigene:3164
SEMA6D Rna ncbigene:80031
HCAR2 Rna ncbigene:338442
SEMA6C Rna ncbigene:10500
ARF6 Rna ncbigene:382
RXRB Rna ncbigene:6257
RPTOR Rna ncbigene:57521
S1PR4 Rna ncbigene:8698
CD36 Rna ncbigene:948
CD83 Rna ncbigene:9308
CD81 Rna ncbigene:975
VEGFA Rna ncbigene:7422
CCN4 Rna ncbigene:8840
BMP2 Rna ncbigene:650
HDGF Rna ncbigene:3068
NOS2 Rna ncbigene:4843
LONP2 Rna ncbigene:83752
ELAVL1 GeneProduct ncbigene:1994
IMP3 GeneProduct ncbigene:55272
NFATC4 GeneProduct ncbigene:4776
NFKB1 GeneProduct ncbigene:4790
RELA GeneProduct ncbigene:5970
CTNNB1 GeneProduct ncbigene:1499
GSK3B GeneProduct ncbigene:2932
NFATC4 GeneProduct ncbigene:4776
BSG Rna ncbigene:682
FN1 Rna ncbigene:2335
CNTN2 Rna ncbigene:6900
ICAM1 Rna ncbigene:3383
SPP1 Rna ncbigene:6696
ITGA2B Rna ncbigene:3674
RELA GeneProduct ncbigene:5970
COL1A1 Rna ncbigene:1277
COL3A1 Rna ncbigene:1281
COL1A2 Rna ncbigene:1278
DES Rna ncbigene:1674
MYH7 Rna ncbigene:4625
ACTA1 Rna ncbigene:58
TMSB4X Rna ncbigene:7114
ACTA2 Rna ncbigene:59
SNTB1 Rna ncbigene:6641
CRYGC Rna ncbigene:1420
LMNB2 Rna ncbigene:84823
KLC1 Rna ncbigene:3831
TF Rna ncbigene:7018
CETP Rna ncbigene:1071
RAE1 Rna ncbigene:8480
B2M Rna ncbigene:567
ABCF1 Rna ncbigene:23
ARL4D Rna ncbigene:379
TOMM40 Rna ncbigene:10452
RANGAP1 Rna ncbigene:5905
PKN1 Rna ncbigene:5585
KITLG Rna ncbigene:4254
BAZ1B Rna ncbigene:9031
STK40 Rna ncbigene:83931
HDAC3 Rna ncbigene:8841
USP5 Rna ncbigene:8078
FBXW7 Rna ncbigene:55294
ADIPOQ Rna ncbigene:9370
NR0B2 Rna ncbigene:8431
NDUFC1 Rna ncbigene:4717
ZDHHC7 Rna ncbigene:55625
GPAT4 Rna ncbigene:137964
HMOX1 Rna ncbigene:3162
ENO1 Rna ncbigene:2023
UGGT1 Rna ncbigene:56886
PYGB Rna ncbigene:5834
LARS2 Rna ncbigene:23395
PLCG1 Rna ncbigene:5335
APBA2 Rna ncbigene:321
ADAMTS5 Rna ncbigene:11096
STOML1 Rna ncbigene:9399
ZC3H12A Rna ncbigene:80149
ZNF143 Rna ncbigene:7702
FAM186B Rna ncbigene:84070
NRN1 Rna ncbigene:51299
SPON1 Rna ncbigene:10418
STMN1 Rna ncbigene:3925
RPS11 Rna ncbigene:6205
NPPB Rna ncbigene:4879
NPPA Rna ncbigene:4878
KRT31 Rna ncbigene:3881
FUT1 Rna ncbigene:2523
CA11 Rna ncbigene:770
ANP32A Rna ncbigene:8125
LRRFIP1 Rna ncbigene:9208
NCAPH2 Rna ncbigene:29781
ZBTB7A Rna ncbigene:51341
RND2 Rna ncbigene:8153
ALS2 Rna ncbigene:57679
ARFGAP1 Rna ncbigene:55738
PRM1 Rna ncbigene:5619
KIFC3 Rna ncbigene:3801
PWWP3A Rna ncbigene:84939
CENPB Rna ncbigene:1059
HOXD8 Rna ncbigene:3234
BPGM Rna ncbigene:669
ACADS Rna ncbigene:35
CPT1A Rna ncbigene:1374
HADH Rna ncbigene:3033
PTGS2 Rna ncbigene:5743
PPT2 Rna ncbigene:9374
ACOD1 Rna ncbigene:730249
COX17 Rna ncbigene:10063
ECH1 Rna ncbigene:1891
TGM2 Rna ncbigene:7052
PLD1 Rna ncbigene:5337
PIGT Rna ncbigene:51604
UGT2B10 Rna ncbigene:7365
ARG1 Rna ncbigene:383
IRAK4 GeneProduct ncbigene:12682231
MAP2K7 GeneProduct ncbigene:5609
STAT3 GeneProduct ncbiprotein:NP_644805.1
BAX GeneProduct ncbigene:581
AMPK1 GeneProduct ncbigene:5562
PARP1 GeneProduct ncbigene:142
RPS6KB1 GeneProduct ncbigene:6198
IL37 Protein ncbigene:27178
ULBP2 Rna ncbigene:80328
MYD88 Rna ncbigene:4615
RFX5 Rna ncbigene:5993
TBX21 Rna ncbigene:30009
STAT3 GeneProduct ncbiprotein:NP_644805.1
PRKCD GeneProduct ncbigene:5580
BAD Rna ncbigene:572


  1. Rex DAB, Agarwal N, Prasad TSK, Kandasamy RK, Subbannayya Y, Pinto SM. A comprehensive pathway map of IL-18-mediated signalling. J Cell Commun Signal. 2020 Jun;14(2):257–66. PubMed Europe PMC Scholia