_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e10
_enti_e2
_enti_e4
_enti_e3
_enti_e55
_enti_e59
_enti_e53
_enti_e52
_enti_e56
_enti_e51
_enti_e50
_enti_e54
_enti_e57
_enti_e58
_enti_e61
_enti_e60
_enti_e62
g1_fact_g1
g2_fact_g12
g2_fact_g13
g1_fact_g14
p1_propro_p1
PMID: 14698033, 12740443
interferon (IFN)-γ and lipopolysaccharide (LPS) repress the expression of PPARγ.
c5 cso30:c:InputInhibitor connector
c9 cso30:c:InputInhibitor connector
c1 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 14698033
LPS binds to TLRs.
c2 cso30:c:InputProcess connector
c3 cso30:c:InputProcess connector
c4 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 14698033
IFN-gamma binds to IFN-gammaR.
c6 cso30:c:InputProcess connector
c8 cso30:c:InputProcess connector
c7 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 14698033, 10657851
macrophages express and regulate the enzyme aromatase, which converts serum dehydroepiandrosterone (DHEA) into the immunomodulatory estrogens 3β,17β-androstenediol and androstenedione.
c10 cso30:c:InputProcess connector
c13 cso30:c:InputAssociation connector
c11 cso30:c:OutputProcess connector
c12 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 14698033, 8078106, 12855575
Following LPS stimulation microglia and dendritic cells are able to produce 1,25(OH)2D3.
c15 cso30:c:InputAssociation connector
c14 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 14698033
ligands for PPAR-alpha are leukotriene (LT)B4 and 8(S)-hydroxyecosatetraenoic acid (HETE), whereas 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), 15-HETE and 13-hydroxyoctadecadienoic acid (HODE) act as ligands for PPARγ.
c16 cso30:c:InputProcess connector
c17 cso30:c:InputProcess connector
c18 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 14698033
ligands for PPAR-alpha are leukotriene (LT)B4 and 8(S)-hydroxyecosatetraenoic acid (HETE), whereas 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), 15-HETE and 13-hydroxyoctadecadienoic acid (HODE) act as ligands for PPARγ.
c19 cso30:c:InputProcess connector
c20 cso30:c:InputProcess connector
c21 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 14698033
ligands for PPAR-alpha are leukotriene (LT)B4 and 8(S)-hydroxyecosatetraenoic acid (HETE), whereas 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), 15-HETE and 13-hydroxyoctadecadienoic acid (HODE) act as ligands for PPARγ.
c22 cso30:c:InputProcess connector
c23 cso30:c:InputProcess connector
c24 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 14698033
ligands for PPAR-alpha are leukotriene (LT)B4 and 8(S)-hydroxyecosatetraenoic acid (HETE), whereas 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), 15-HETE and 13-hydroxyoctadecadienoic acid (HODE) act as ligands for PPARγ.
c25 cso30:c:InputProcess connector
c26 cso30:c:InputProcess connector
c27 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 14698033
ligands for PPAR-alpha are leukotriene (LT)B4 and 8(S)-hydroxyecosatetraenoic acid (HETE), whereas 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), 15-HETE and 13-hydroxyoctadecadienoic acid (HODE) act as ligands for PPARγ.
c28 cso30:c:InputProcess connector
c29 cso30:c:InputProcess connector
c30 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 14698033, 10432118, 11726648
13-HODE and 15-HETE can be enzymatically generated by the IL-4 inducible 12/15-lipoxygenase, suggesting that IL-4 can coordinately regulate the expression and activity of PPARγ.
c31 cso30:c:InputProcess connector
c36 cso30:c:InputAssociation connector
c32 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 14698033, 10432118, 11726648
13-HODE and 15-HETE can be enzymatically generated by the IL-4 inducible 12/15-lipoxygenase, suggesting that IL-4 can coordinately regulate the expression and activity of PPARγ.
c33 cso30:c:InputProcess connector
c35 cso30:c:InputAssociation connector
c34 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 14698033, 10432118, 11726648
13-HODE and 15-HETE can be enzymatically generated by the IL-4 inducible 12/15-lipoxygenase, suggesting that IL-4 can coordinately regulate the expression and activity of PPARγ.
c44 cso30:c:InputAssociation connector
c37 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 14698033, 10432118, 11726648
13-HODE and 15-HETE can be enzymatically generated by the IL-4 inducible 12/15-lipoxygenase, suggesting that IL-4 can coordinately regulate the expression and activity of PPARγ.
c39 cso30:c:InputAssociation connector
c43 cso30:c:InputAssociation connector
c38 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 14698033
IL4 binds to IL4R
c40 cso30:c:InputProcess connector
c41 cso30:c:InputProcess connector
c42 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 14698033, 11504730, 9334194
In macrophages, sterol 27-hydrolase (CYP27) is able to modify cholesterol into a naturally occurring ligand for LXRs.
PMID: 14698033, 9874807, 14512442, 9013544, 8878485
LXRs are activated by specific oxidized forms of cholesterol (oxysterols)such as 24(S)-hydroxycholesterol and 22(R)-hydroxycholesterol, or by certain intermediates of the cholesterol biosynthetic pathway such as 24(S),25-epoxycholesterol.
c45 cso30:c:InputProcess connector
c53 cso30:c:InputAssociation connector
c46 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 14698033, 9874807, 14512442, 9013544, 8878485
LXRs are activated by specific oxidized forms of cholesterol (oxysterols)such as 24(S)-hydroxycholesterol and 22(R)-hydroxycholesterol, or by certain intermediates of the cholesterol biosynthetic pathway such as 24(S),25-epoxycholesterol.
PMID: 14698033, 11504730, 9334194
In macrophages, sterol 27-hydrolase (CYP27) is able to modify cholesterol into a naturally occurring ligand for LXRs.
c47 cso30:c:InputProcess connector
c51 cso30:c:InputAssociation connector
c48 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 14698033, 11504730, 9334194
In macrophages, sterol 27-hydrolase (CYP27) is able to modify cholesterol into a naturally occurring ligand for LXRs.
PMID: 14698033, 9874807, 14512442, 9013544, 8878485
LXRs are activated by specific oxidized forms of cholesterol (oxysterols)such as 24(S)-hydroxycholesterol and 22(R)-hydroxycholesterol, or by certain intermediates of the cholesterol biosynthetic pathway such as 24(S),25-epoxycholesterol.
c49 cso30:c:InputProcess connector
c52 cso30:c:InputAssociation connector
c50 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 14698033, 9874807, 14512442, 9013544, 8878485
LXRs are activated by specific oxidized forms of cholesterol (oxysterols)such as 24(S)-hydroxycholesterol and 22(R)-hydroxycholesterol, or by certain intermediates of the cholesterol biosynthetic pathway such as 24(S),25-epoxycholesterol.
c54 cso30:c:InputProcess connector
c55 cso30:c:InputProcess connector
c56 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 14698033, 9874807, 14512442, 9013544, 8878485
LXRs are activated by specific oxidized forms of cholesterol (oxysterols)such as 24(S)-hydroxycholesterol and 22(R)-hydroxycholesterol, or by certain intermediates of the cholesterol biosynthetic pathway such as 24(S),25-epoxycholesterol.
c57 cso30:c:InputProcess connector
c58 cso30:c:InputProcess connector
c59 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 14698033, 9874807, 14512442, 9013544, 8878485
LXRs are activated by specific oxidized forms of cholesterol (oxysterols)such as 24(S)-hydroxycholesterol and 22(R)-hydroxycholesterol, or by certain intermediates of the cholesterol biosynthetic pathway such as 24(S),25-epoxycholesterol.
c60 cso30:c:InputProcess connector
c61 cso30:c:InputProcess connector
c62 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 14698033, 7823959, 7659084
One established mechanism involves direct interaction between GR and negatively regulated transcription factors such as AP-1 and NF-κB.
c63 cso30:c:InputProcess connector
c64 cso30:c:InputProcess connector
c65 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 14698033, 7823959, 7659084
One established mechanism involves direct interaction between GR and negatively regulated transcription factors such as AP-1 and NF-κB.
c66 cso30:c:InputProcess connector
c67 cso30:c:InputProcess connector
c68 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 14698033, 11726533
VDR also inhibits inflammatory gene expression by downregulating NF-κB activation or by inducing the expression of both transforming growth factor (TGF)-β and IL-4.
c69 cso30:c:InputProcess connector
c71 cso30:c:InputInhibitor connector
c70 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 14698033, 11726533
VDR also inhibits inflammatory gene expression by downregulating NF-κB activation or by inducing the expression of both transforming growth factor (TGF)-β and IL-4.
c73 cso30:c:InputAssociation connector
c72 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 14698033, 11726533
VDR also inhibits inflammatory gene expression by downregulating NF-κB activation or by inducing the expression of both transforming growth factor (TGF)-β and IL-4.
c75 cso30:c:InputAssociation connector
c74 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 14698033, 12970571
PPARδ represses inflammatory genes including the chemokine monocyte-chemoattractant protein-1 (MCP-1), IL-1β and the metalloproteinase MMP-9 by an unconventional ligand-dependent transcriptional mechanism involving the binding of PPARδ to transcriptional repressors.
c77 cso30:c:InputInhibitor connector
c76 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 14698033, 12970571
PPARδ represses inflammatory genes including the chemokine monocyte-chemoattractant protein-1 (MCP-1), IL-1β and the metalloproteinase MMP-9 by an unconventional ligand-dependent transcriptional mechanism involving the binding of PPARδ to transcriptional repressors.
c79 cso30:c:InputInhibitor connector
c78 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 14698033, 12970571
PPARδ represses inflammatory genes including the chemokine monocyte-chemoattractant protein-1 (MCP-1), IL-1β and the metalloproteinase MMP-9 by an unconventional ligand-dependent transcriptional mechanism involving the binding of PPARδ to transcriptional repressors.
c81 cso30:c:InputInhibitor connector
c80 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 14698033, 3513311
Like most cells, macrophages take up circulating lipoproteins via the low-density lipoprotein (LDL) receptor.
c82 cso30:c:InputProcess connector
c83 cso30:c:InputProcess connector
c84 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 14698033, 9150132
Excess cholesterol inhibits proteolytic activation of sterol regulatory element binding proteins (SREBPs), which are transcription factors that promote cholesterol and triglyceride biosynthesis and LDL receptor expression.
c85 cso30:c:InputProcess connector
c87 cso30:c:InputInhibitor connector
c86 cso30:c:OutputProcess connector
p32_propro_p32
PMID: 14698033, 9150132
Excess cholesterol inhibits proteolytic activation of sterol regulatory element binding proteins (SREBPs), which are transcription factors that promote cholesterol and triglyceride biosynthesis and LDL receptor expression.
c89 cso30:c:InputAssociation connector
c88 cso30:c:OutputProcess connector
p33_propro_p33
PMID: 14698033, 9823020
Resident macrophages also secrete molecules that modify extracellular LDL, e.g. by oxidation (oxLDL), converting it into a form that is efficiently recognized by macrophage scavenger receptors, such as CD36.
c90 cso30:c:InputProcess connector
c91 cso30:c:InputProcess connector
c92 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 14698033, 10858438, 10968783, 11035776, 10924356
Studies have established the connection between nuclear receptor action and reverse cholesterol transport by demonstrating that LXRs directly regulate ABCA1 expression and cholesterol efflux in human and murine cells, including macrophages.
c94 cso30:c:InputAssociation connector
c93 cso30:c:OutputProcess connector
p35_propro_p35
PMID: 14698033, 10858438, 10968783, 11035776, 10924356
Studies have established the connection between nuclear receptor action and reverse cholesterol transport by demonstrating that LXRs directly regulate ABCA1 expression and cholesterol efflux in human and murine cells, including macrophages.
c95 cso30:c:InputAssociation connector
c103 cso30:c:InputAssociation connector
c96 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 14698033, 10882340
ABCA1 transports intracellular phospholipids and cholesterol to exogenous nascent HDL particles, which contain lipid-poor apolipoprotein (apo) acceptors, such as apoAI.
c97 cso30:c:InputProcess connector
c99 cso30:c:InputAssociation connector
c98 cso30:c:OutputProcess connector
p37_propro_p37
PMID: 14698033, 10882340
ABCA1 transports intracellular phospholipids and cholesterol to exogenous nascent HDL particles, which contain lipid-poor apolipoprotein (apo) acceptors, such as apoAI.
c100 cso30:c:InputProcess connector
c102 cso30:c:InputAssociation connector
c101 cso30:c:OutputProcess connector
p38_propro_p38
PMID: 14698033, 11172721, 11135616
PPARalpha and PPARγ upregulate the expression of ABCA1 and promote cholesterol efflux in human macrophages through a transcriptional cascade mediated by LXR-alpha.
c105 cso30:c:InputAssociation connector
c104 cso30:c:OutputProcess connector
p39_propro_p39
PMID: 14698033, 11172721, 11135616
PPARalpha and PPARγ upregulate the expression of ABCA1 and promote cholesterol efflux in human macrophages through a transcriptional cascade mediated by LXR-alpha.
c107 cso30:c:InputAssociation connector
c106 cso30:c:OutputProcess connector
p40_propro_p40
PMID: 14698033, 11409902, 12574149
PPAR alpha and PPARγ have been also shown to down-regulate the expression of macrophage cholesteryl ester hydrolase (CEH), an enzyme required for hydrolysis and release of cholesterol from foam cells.
c109 cso30:c:InputInhibitor connector
c110 cso30:c:InputInhibitor connector
c108 cso30:c:OutputProcess connector
p41_propro_p41
PMID: 14698033, 12740443, 11909955, 10799558
LXRs and PPARγ are able to directly induce the expression of another member of the ATP binding cassette family, ABCG1.
c112 cso30:c:InputAssociation connector
c111 cso30:c:OutputProcess connector
p42_propro_p42
c114 cso30:c:InputAssociation connector
c113 cso30:c:OutputProcess connector
p43_propro_p43
PMID: 14698033, 11090130, 11287605
In many cellular types, including macrophages, the expression of the transcription factor SREBP-1c is induced by LXR activation.
c116 cso30:c:InputAssociation connector
c115 cso30:c:OutputProcess connector
p44_propro_p44
PMID: 14698033, 11090130, 11287605
In many cellular types, including macrophages, the expression of the transcription factor SREBP-1c is induced by LXR activation.
c118 cso30:c:InputAssociation connector
c119 cso30:c:InputAssociation connector
c117 cso30:c:OutputProcess connector
p45_propro_p45
PMID: 14698033
SREBP1c positively regulates the expression of a number of enzymes involved in fatty acid synthesis and triglyceride formation, including fatty acid synthase and stearoyl coenzyme A desaturase.
c121 cso30:c:InputAssociation connector
c120 cso30:c:OutputProcess connector
p46_propro_p46
PMID: 14698033
SREBP1c positively regulates the expression of a number of enzymes involved in fatty acid synthesis and triglyceride formation, including fatty acid synthase and stearoyl coenzyme A desaturase.
c122 cso30:c:InputAssociation connector
c124 cso30:c:InputAssociation connector
c123 cso30:c:OutputProcess connector
p47_propro_p47
PMID: 14698033
SREBP1c positively regulates the expression of a number of enzymes involved in fatty acid synthesis and triglyceride formation, including fatty acid synthase and stearoyl coenzyme A desaturase.
c125 cso30:c:InputAssociation connector
c126 cso30:c:OutputProcess connector
p48_propro_p48
PMID: 14698033
SREBP1c positively regulates the expression of a number of enzymes involved in fatty acid synthesis and triglyceride formation, including fatty acid synthase and stearoyl coenzyme A desaturase.
c127 cso30:c:InputAssociation connector
c129 cso30:c:InputAssociation connector
c128 cso30:c:OutputProcess connector
PPARG_enti_G011580
PPARG
LPS_enti_MO000016882
LPS
TLRs_enti_MO000019395
TLRs
LPS:TLRs_enti_e5
LPS:TLRs
IFN-gamma_enti_e6
IFN-gamma
IFN-gamma:IFN-gammaR_enti_e11
IFN-gamma:IFN-gammaR
IFN-gammaR_enti_e12
IFN-gammaR
aromatase_enti_e13
aromatase
DHEA_enti_e14
DHEA
androstenedione_enti_e15
androstenedione
3β,17β-androstenediol_enti_e16
3β,17β-androstenediol
1,25(OH)2D3_enti_e17
1,25(OH)2D3
LTB4_enti_MO000033519
LTB4
PPARalpha (NR1C1)_enti_MO000033504
PPARalpha (NR1C1)
LTB4:PPAR-alpha_enti_e18
LTB4:PPAR-alpha
8(S)-HETE_enti_MO000033583
8(S)-HETE
8(S)-HETE:PPARalpha (NR1C1)_enti_MO000110538
8(S)-HETE:PPARalpha (NR1C1)
15d-PGJ2_enti_MO000033561
15d-PGJ2
15d-PGJ2:PPARgamma (NR1C3)_enti_MO000038949
15d-PGJ2:PPARgamma (NR1C3)
PPARgamma (NR1C3)_enti_MO000022492
PPARgamma (NR1C3)
15-HETE_enti_MO000038975
15-HETE
15-HETE:PPARgamma_enti_e19
15-HETE:PPARgamma
13-HODE_enti_MO000108309
13-HODE
13-HODE:PPARgamma_enti_e20
13-HODE:PPARgamma
arachidonic acid_enti_MO000000310
arachidonic acid
12/15-lipoxygenase_enti_e21
12/15-lipoxygenase
12/15-lipoxygenase_enti_e22
12/15-lipoxygenase
IL-4_enti_MO000017053
IL-4
IL-4R_enti_MO000017059
IL-4R
IL4:IL4R_enti_e23
IL4:IL4R
cholesterol_enti_MO000056221
cholesterol
24(S)-hydroxycholesterol_enti_MO000114348
24(S)-hydroxycholesterol
24(S),25-epoxycholesterol_enti_MO000114356
24(S),25-epoxycholesterol
22(R)-hydroxycholesterol_enti_e24
22(R)-hydroxycholesterol
CYP27_enti_e25
CYP27
LXR_enti_MO000056002
LXR
24(S),25-epoxycholesterol:LXR_enti_e26
24(S),25-epoxycholesterol:LXR
24(S)-hydroxycholesterol:LXR_enti_e27
24(S)-hydroxycholesterol:LXR
22(R)-hydroxycholesterol:LXR_enti_e28
22(R)-hydroxycholesterol:LXR
GR (NR3C1)_enti_MO000000050
GR (NR3C1)
AP-1_enti_MO000000276
AP-1
NF-kappaB_enti_MO000000058
NF-kappaB
GR:AP1_enti_e29
GR:AP1
GR:NF-kappaB_enti_e30
GR:NF-kappaB
NF-kappaB{active}_enti_e31
NF-kappaB{active}
VDR (NR1I1)_enti_MO000021494
VDR (NR1I1)
TGF-beta_enti_e32
TGF-beta
IL-4_enti_G010469
IL-4
PPARbeta (NR1C2)_enti_MO000033505
PPARbeta (NR1C2)
MCP1_enti_G010815
MCP1
MMP-9_enti_G010279
MMP-9
IL-1beta_enti_G010389
IL-1beta
LDL receptor_enti_MO000061802
LDL receptor
LDL_enti_MO000000290
LDL
LDL:LDL receptor_enti_e33
LDL:LDL receptor
SREBP_enti_MO000000288
SREBP
SREBP{cleaved}_enti_e34
SREBP{cleaved}
LDL receptor_enti_e35
LDL receptor
oxLDL_enti_MO000107436
oxLDL
CD36_enti_e36
CD36
oxLDL:CD36_enti_e37
oxLDL:CD36
ABCA1_enti_G013072
ABCA1
ABCA1_enti_e38
ABCA1
phospholipids_enti_e39
phospholipids
phospholipids_enti_e40
phospholipids
cholesterol_enti_e41
cholesterol
CEH_enti_e42
CEH
ABCG1_enti_G013114
ABCG1
SREBP-1c_enti_MO000037246
SREBP-1c
SREBP-1C_enti_e43
SREBP-1C
FASN_enti_G010462
FASN
FASN_enti_e44
FASN
stearoyl coenzyme A desaturase_enti_e45
stearoyl coenzyme A desaturase
stearoyl coenzyme A desaturase_enti_e46
stearoyl coenzyme A desaturase