_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e10
_enti_e4
_enti_e2
_enti_e3
_enti_e55
_enti_e11
_enti_e53
_enti_e59
_enti_e5
_enti_e6
_enti_e56
_enti_e54
_enti_e50
_enti_e51
_enti_e52
_enti_e58
_enti_e57
_enti_e61
_enti_e62
_enti_e60
g2_fact_g2
g1_fact_g1
g2_fact_g12
g2_fact_g13
g1_fact_g14
g1_fact_g3
p1_propro_p1
PMID: 15481153
TLR4 is a receptor for Gram- LPS, Respiratory syncytial virus protein F, and other endogenous ligands, such as surfactant protein A and fibronectin fragment.
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 15481153, 14620134, 12960260
TLR belong to a family of PRR that are used to recognize microbial products derived from several classes of microbes, as well as endogenous ligands that represent ‘‘danger signal’’.
c4 cso30:c:InputProcess connector
c6 cso30:c:InputProcess connector
c5 cso30:c:OutputProcess connector
p3_propro_p3
c9 cso30:c:InputProcess connector
c94 cso30:c:InputProcess connector
c8 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 15481153
TLR also contain a highly conserved cytoplasmic Toll-IL-1 receptor (TIR) domain that, through the adaptor molecule MyD88, connects the receptor to the intracellular signaling machinery shared by IL-1 and IL-18.
c10 cso30:c:InputProcess connector
c11 cso30:c:InputProcess connector
c12 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 15481153
TLR3 mediates responses to viral dsRNA.
c13 cso30:c:InputProcess connector
c14 cso30:c:InputProcess connector
c15 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 15481153
This molecule links all TLR, with the possible exception of TLR3, to the complex IRAK1/4- TRAF6, which then leads to the activation of canonical NF-kappaB and MAPKs.
c16 cso30:c:InputProcess connector
c17 cso30:c:InputProcess connector
c19 cso30:c:InputProcess connector
c18 cso30:c:OutputProcess connector
p7_propro_p7
c21 cso30:c:InputProcess connector
c20 cso30:c:InputProcess connector
c22 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 15481153
TLR2, in combination with either TLR1 or TLR6, recognizes several products including peptidoglycan, bacterial lipopeptides, mycobacterial lipoarabinomannan, and yeast zymosan.
c23 cso30:c:InputProcess connector
c24 cso30:c:InputProcess connector
c25 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 15481153
TLR2, in combination with either TLR1 or TLR6, recognizes several products including peptidoglycan, bacterial lipopeptides, mycobacterial lipoarabinomannan, and yeast zymosan.
c26 cso30:c:InputProcess connector
c27 cso30:c:InputProcess connector
c28 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 15481153
TLR2, in combination with either TLR1 or TLR6, recognizes several products including peptidoglycan, bacterial lipopeptides, mycobacterial lipoarabinomannan, and yeast zymosan.
c32 cso30:c:InputProcess connector
c33 cso30:c:InputProcess connector
c34 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 15481153, 12539043, 12855817, 12692549
This pathway relies on a third adaptor called TRIF/TICAM (Oshiumi et al., 2003; Yamamoto et al., 2003a) that links TLR3 and TLR4 to the kinase complex IKKepsilon/TBK1, which in turn activates the transcription factor IRF3.
c29 cso30:c:InputProcess connector
c31 cso30:c:InputProcess connector
c30 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 15481153
TLR2, in combination with either TLR1 or TLR6, recognizes several products including peptidoglycan, bacterial lipopeptides, mycobacterial lipoarabinomannan, and yeast zymosan.
c35 cso30:c:InputProcess connector
c36 cso30:c:InputProcess connector
c37 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 15481153
TLR4 is a receptor for Gram- LPS, Respiratory syncytial virus protein F, and other endogenous ligands, such as surfactant protein A and fibronectin fragment.
c38 cso30:c:InputProcess connector
c39 cso30:c:InputProcess connector
c40 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 15481153
TLR4 is a receptor for Gram- LPS, Respiratory syncytial virus protein F, and other endogenous ligands, such as surfactant protein A and fibronectin fragment.
c41 cso30:c:InputProcess connector
c42 cso30:c:InputProcess connector
c43 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 15481153
TLR4 is a receptor for Gram- LPS, Respiratory syncytial virus protein F, and other endogenous ligands, such as surfactant protein A and fibronectin fragment.
c44 cso30:c:InputProcess connector
c45 cso30:c:InputProcess connector
c46 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 15481153
TLR5 recognizes bacterial flagellin.
c47 cso30:c:InputProcess connector
c48 cso30:c:InputProcess connector
c49 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 15481153
TLR7 and TLR8 are receptors for ssRNA found in endosomal compartments and antiviral imidazoquinoline drugs that are structural mimetics of ssRNA.
c50 cso30:c:InputProcess connector
c51 cso30:c:InputProcess connector
c52 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 15481153
TLR7 and TLR8 are receptors for ssRNA found in endosomal compartments and antiviral imidazoquinoline drugs that are structural mimetics of ssRNA.
c53 cso30:c:InputProcess connector
c55 cso30:c:InputProcess connector
c54 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 15481153
TLR7 and TLR8 are receptors for ssRNA found in endosomal compartments and antiviral imidazoquinoline drugs that are structural mimetics of ssRNA.
c56 cso30:c:InputProcess connector
c57 cso30:c:InputProcess connector
c58 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 15481153
TLR7 and TLR8 are receptors for ssRNA found in endosomal compartments and antiviral imidazoquinoline drugs that are structural mimetics of ssRNA.
c59 cso30:c:InputProcess connector
c60 cso30:c:InputProcess connector
c61 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 15481153
TLR9 mediates responses to bacterial CpG DNA.
c62 cso30:c:InputProcess connector
c63 cso30:c:InputProcess connector
c64 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 15481153, 15001781
TLR11 mediates response to uropathogenic bacteria, although the nature of the agonist has not been identified.
c65 cso30:c:InputProcess connector
c66 cso30:c:InputProcess connector
c67 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 15481153
This molecule links all TLR, with the possible exception of TLR3, to the complex IRAK1/4- TRAF6, which then leads to the activation of canonical NF-kappaB and MAPKs.
c68 cso30:c:InputProcess connector
c70 cso30:c:InputProcess connector
c69 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 15481153
This molecule links all TLR, with the possible exception of TLR3, to the complex IRAK1/4- TRAF6, which then leads to the activation of canonical NF-kappaB and MAPKs.
c71 cso30:c:InputProcess connector
c75 cso30:c:InputAssociation connector
c72 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 15481153
This molecule links all TLR, with the possible exception of TLR3, to the complex IRAK1/4- TRAF6, which then leads to the activation of canonical NF-kappaB and MAPKs.
c73 cso30:c:InputProcess connector
c76 cso30:c:InputAssociation connector
c74 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 15481153
The fact that different TLR can induce such an array of responses suggest that they possess the ability to selectively activate distinct signaling pathways, which include the MAP kinases p38, c-Jun N-terminal kinase, ERK1/2, the transcription factors NF-kappaB and IRF-3, the PI3 kinase, and caspase-1.
c77 cso30:c:InputProcess connector
c79 cso30:c:InputAssociation connector
c78 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 15481153
The fact that different TLR can induce such an array of responses suggest that they possess the ability to selectively activate distinct signaling pathways, which include the MAP kinases p38, c-Jun N-terminal kinase, ERK1/2, the transcription factors NF-kappaB and IRF-3, the PI3 kinase, and caspase-1.
c80 cso30:c:InputProcess connector
c82 cso30:c:InputAssociation connector
c81 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 15481153
The fact that different TLR can induce such an array of responses suggest that they possess the ability to selectively activate distinct signaling pathways, which include the MAP kinases p38, c-Jun N-terminal kinase, ERK1/2, the transcription factors NF-kappaB and IRF-3, the PI3 kinase, and caspase-1.
c83 cso30:c:InputProcess connector
c85 cso30:c:InputAssociation connector
c84 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 15481153
The fact that different TLR can induce such an array of responses suggest that they possess the ability to selectively activate distinct signaling pathways, which include the MAP kinases p38, c-Jun N-terminal kinase, ERK1/2, the transcription factors NF-kappaB and IRF-3, the PI3 kinase, and caspase-1.
c86 cso30:c:InputProcess connector
c88 cso30:c:InputAssociation connector
c87 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 15481153, 11544529, 11526399
The activation of this pathway by TLR2 and TLR4 is dependent on an additional TIR-containing adaptor called TIRAP/MALthat works in conjunction with MyD88.
c89 cso30:c:InputProcess connector
c90 cso30:c:InputProcess connector
c91 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 15481153, 11544529, 11526399
The activation of this pathway by TLR2 and TLR4 is dependent on an additional TIR-containing adaptor called TIRAP/MALthat works in conjunction with MyD88.
c7 cso30:c:InputProcess connector
c92 cso30:c:InputProcess connector
c93 cso30:c:OutputProcess connector
p32_propro_p32
PMID: 15481153, 11544529, 11526399
The activation of this pathway by TLR2 and TLR4 is dependent on an additional TIR-containing adaptor called TIRAP/MALthat works in conjunction with MyD88.
c95 cso30:c:InputProcess connector
c96 cso30:c:InputProcess connector
c97 cso30:c:OutputProcess connector
p33_propro_p33
PMID: 15481153, 14556004
TRAM, the most recently characterized TIR-containing adaptor, also appears to be required for both MyD88-dependent and MyD88-independent responses induced by TLR4.
c98 cso30:c:InputProcess connector
c99 cso30:c:InputProcess connector
c100 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 15481153, 12539043, 12855817, 12692549
This pathway relies on a third adaptor called TRIF/TICAM (Oshiumi et al., 2003; Yamamoto et al., 2003a) that links TLR3 and TLR4 to the kinase complex IKKepsilon/TBK1, which in turn activates the transcription factor IRF3.
c101 cso30:c:InputProcess connector
c102 cso30:c:InputProcess connector
c103 cso30:c:OutputProcess connector
p35_propro_p35
PMID: 15481153, 12539043, 12855817, 12692549
This pathway relies on a third adaptor called TRIF/TICAM (Oshiumi et al., 2003; Yamamoto et al., 2003a) that links TLR3 and TLR4 to the kinase complex IKKepsilon/TBK1, which in turn activates the transcription factor IRF3.
c104 cso30:c:InputProcess connector
c105 cso30:c:InputProcess connector
c106 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 15481153, 12539043, 12855817, 12692549
This pathway relies on a third adaptor called TRIF/TICAM (Oshiumi et al., 2003; Yamamoto et al., 2003a) that links TLR3 and TLR4 to the kinase complex IKKepsilon/TBK1, which in turn activates the transcription factor IRF3.
c107 cso30:c:InputProcess connector
c109 cso30:c:InputAssociation connector
c108 cso30:c:OutputProcess connector
p37_propro_p37
PMID: 15481153, 12354379, 11698465
IRF3 is responsible for the induction of a group of genes specific for TLR3/4 stimulation, such as IFN-beta and IP-10.
PMID: 15481153
For example, in human DC TLR3 is able to induce IP-10 and IL-15 to similar levels as TLR4, yet it induces IFN-beta only very weakly.
c112 cso30:c:InputAssociation connector
c110 cso30:c:OutputProcess connector
p38_propro_p38
PMID: 15481153, 12354379, 11698465
IRF3 is responsible for the induction of a group of genes specific for TLR3/4 stimulation, such as IFN-beta and IP-10.
PMID: 15481153
Thus, while TLR2 activation is unable to induce Th1-specific factors (IP-10, IFN-beta, IL-12, and IL-15), it is at the same time capable of blocking the induction of some of them (IL-12 and IP-10) by TLR4 and TLR3.
PMID: 15481153
For example, in human DC TLR3 is able to induce IP-10 and IL-15 to similar levels as TLR4, yet it induces IFN-beta only very weakly.
c113 cso30:c:InputAssociation connector
c229 cso30:c:InputInhibitor connector
c111 cso30:c:OutputProcess connector
p39_propro_p39
PMID: 15481153
Furthermore, TRIF is capable of leading to the activation of NF-kappaB and MAPKs, and appears to be the only adaptor used by TLR3.
c114 cso30:c:InputProcess connector
c118 cso30:c:InputAssociation connector
c115 cso30:c:OutputProcess connector
p40_propro_p40
PMID: 15481153
Furthermore, TRIF is capable of leading to the activation of NF-kappaB and MAPKs, and appears to be the only adaptor used by TLR3.
c116 cso30:c:InputProcess connector
c119 cso30:c:InputAssociation connector
c117 cso30:c:OutputProcess connector
p41_propro_p41
PMID: 15481153
Furthermore, TRIF is capable of leading to the activation of NF-kappaB and MAPKs, and appears to be the only adaptor used by TLR3.
c120 cso30:c:InputAssociation connector
c122 cso30:c:InputProcess connector
c123 cso30:c:OutputProcess connector
p42_propro_p42
PMID: 15481153
Furthermore, TRIF is capable of leading to the activation of NF-kappaB and MAPKs, and appears to be the only adaptor used by TLR3.
c121 cso30:c:InputAssociation connector
c124 cso30:c:InputProcess connector
c125 cso30:c:OutputProcess connector
p43_propro_p43
PMID: 15481153
TLR signaling initiates DC maturation, a differentiation process in which the antigen is captured and processed into peptides that are then presented in the context of MHC class II molecules.
c126 cso30:c:InputAssociation connector
p44_propro_p44
PMID: 15481153
Various TLR agonists activate mast cells, eosinophil, neutrophils, B cells, endothelial cells, and several types of epithelia, and regulate proliferation and apoptosis of different cell types.
c127 cso30:c:InputAssociation connector
p45_propro_p45
PMID: 15481153
Various TLR agonists activate mast cells, eosinophil, neutrophils, B cells, endothelial cells, and several types of epithelia, and regulate proliferation and apoptosis of different cell types.
c128 cso30:c:InputAssociation connector
p46_propro_p46
PMID: 15481153
NF-kappaB and MAPK family members were activated to the same extent and with similar kinetics by both TLR2 and TLR4 agonists in the DC.
c129 cso30:c:InputProcess connector
c137 cso30:c:InputAssociation connector
c130 cso30:c:OutputProcess connector
p47_propro_p47
PMID: 15481153
NF-kappaB and MAPK family members were activated to the same extent and with similar kinetics by both TLR2 and TLR4 agonists in the DC.
c133 cso30:c:InputProcess connector
c138 cso30:c:InputAssociation connector
c134 cso30:c:OutputProcess connector
p48_propro_p48
PMID: 15481153
NF-kappaB and MAPK family members were activated to the same extent and with similar kinetics by both TLR2 and TLR4 agonists in the DC.
c131 cso30:c:InputProcess connector
c139 cso30:c:InputAssociation connector
c132 cso30:c:OutputProcess connector
p49_propro_p49
PMID: 15481153
NF-kappaB and MAPK family members were activated to the same extent and with similar kinetics by both TLR2 and TLR4 agonists in the DC.
c135 cso30:c:InputProcess connector
c140 cso30:c:InputAssociation connector
c136 cso30:c:OutputProcess connector
p58_propro_p58
PMID: 15481153
TLR2 and TLR4 agonists were also equally capable of inducing DC maturation as measured by the up-regulation of several cell surface markers such as CD40, CD86, HLA-DR, and CD83.
c157 cso30:c:InputAssociation connector
c158 cso30:c:InputAssociation connector
c159 cso30:c:InputAssociation connector
c160 cso30:c:InputAssociation connector
p59_propro_p59
PMID: 15481153
Among the several cytokines and chemokines that were analyzed, IL-12p70, IP-10, IFNb, and IL-15 expression was exclusively induced by the TLR4 agonist LPS and not by TLR2 agonists.
PMID: 15481153
IFN-beta, IFIT1, and ISG15 belong to the primary response group.
c167 cso30:c:InputAssociation connector
c161 cso30:c:OutputProcess connector
p60_propro_p60
PMID: 15481153
Among the several cytokines and chemokines that were analyzed, IL-12p70, IP-10, IFNb, and IL-15 expression was exclusively induced by the TLR4 agonist LPS and not by TLR2 agonists.
PMID: 15481153, 15001781
IP-10 also appears to be part of this group, although it has been suggested otherwise.
PMID: 15481153
Thus, while TLR2 activation is unable to induce Th1-specific factors (IP-10, IFN-beta, IL-12, and IL-15), it is at the same time capable of blocking the induction of some of them (IL-12 and IP-10) by TLR4 and TLR3.
c168 cso30:c:InputAssociation connector
c230 cso30:c:InputInhibitor connector
c162 cso30:c:OutputProcess connector
p61_propro_p61
PMID: 15481153
Among the several cytokines and chemokines that were analyzed, IL-12p70, IP-10, IFNb, and IL-15 expression was exclusively induced by the TLR4 agonist LPS and not by TLR2 agonists.
PMID: 15481153
Thus, while TLR2 activation is unable to induce Th1-specific factors (IP-10, IFN-beta, IL-12, and IL-15), it is at the same time capable of blocking the induction of some of them (IL-12 and IP-10) by TLR4 and TLR3.
c165 cso30:c:InputAssociation connector
c231 cso30:c:InputInhibitor connector
c163 cso30:c:OutputProcess connector
p62_propro_p62
PMID: 15481153
Among the several cytokines and chemokines that were analyzed, IL-12p70, IP-10, IFN-beta, and IL-15 expression was exclusively induced by the TLR4 agonist LPS and not by TLR2 agonists.
PMID: 15481153
It is currently unclear as to what group other TLR4-specific genes, such as IL12p35 and IL-15, belong to.
c166 cso30:c:InputAssociation connector
c164 cso30:c:OutputProcess connector
p63_propro_p63
PMID: 15481153
In contrast, TLR2 agonists preferentially induced IL-8, IL-10, and IL-23p19.
c172 cso30:c:InputAssociation connector
c169 cso30:c:OutputProcess connector
p64_propro_p64
PMID: 15481153
In contrast, TLR2 agonists preferentially induced IL-8, IL-10, and IL-23p19.
c173 cso30:c:InputAssociation connector
c170 cso30:c:OutputProcess connector
p65_propro_p65
PMID: 15481153
In contrast, TLR2 agonists preferentially induced IL-8, IL-10, and IL-23p19.
c174 cso30:c:InputAssociation connector
c171 cso30:c:OutputProcess connector
p66_propro_p66
PMID: 15481153
The p40 subunit is expressed in large excess of the p35 subunit, which is the limiting factor in controlling IL-12p70 production.
c175 cso30:c:InputAssociation connector
c177 cso30:c:InputInhibitor connector
c176 cso30:c:OutputProcess connector
p67_propro_p67
PMID: 15481153
IL-12p40 can also form homodimers that act as IL-12 receptor antagonist, or can pair with p19 to form IL-23, a novel cytokine whose activities remain poorly characterized.
c178 cso30:c:InputProcess connector
c179 cso30:c:OutputProcess connector
p68_propro_p68
PMID: 15481153
IL-12p40 can also form homodimers that act as IL-12 receptor antagonist, or can pair with p19 to form IL-23, a novel cytokine whose activities remain poorly characterized.
c180 cso30:c:InputProcess connector
c181 cso30:c:InputProcess connector
c182 cso30:c:OutputProcess connector
p69_propro_p69
PMID: 15481153
IL-12p40 can also form homodimers that act as IL-12 receptor antagonist, or can pair with p19 to form IL-23, a novel cytokine whose activities remain poorly characterized.
c183 cso30:c:InputProcess connector
c184 cso30:c:InputProcess connector
c185 cso30:c:OutputProcess connector
p70_propro_p70
PMID: 15481153, 12563297
IL-12 is able to stimulate IFN-gamma production in T cells, and is the key cytokine that directs the development of human and murine Th1 cells.
c187 cso30:c:InputAssociation connector
c188 cso30:c:InputAssociation connector
c186 cso30:c:OutputProcess connector
p71_propro_p71
PMID: 15481153
The fact that TLR4, but not TLR2, is able to induce the p35 subunit of IL-12, suggests that the Th1/ Th2 balance may be directly affected by the action of TLR.
PMID: 15481153
It is currently unclear as to what group other TLR4-specific genes, such as IL12p35 and IL-15, belong to.
c190 cso30:c:InputAssociation connector
c189 cso30:c:OutputProcess connector
p72_propro_p72
PMID: 15481153
It is remarkable that TLR2 stimulation, while failing to induce IL-12p70 release due to defective p35 gene induction, is nevertheless still able to stimulate.
c192 cso30:c:InputAssociation connector
c191 cso30:c:OutputProcess connector
p73_propro_p73
PMID: 15481153
IP-10, a CXC chemokine produced by different cell types in response to IFN-gamma and microbial products, is a chemoattractant for monocytes, NK cells, and, importantly, Th1 cells that preferentially express the IP-10 receptor CXCR3.
c194 cso30:c:InputAssociation connector
c195 cso30:c:InputAssociation connector
c193 cso30:c:OutputProcess connector
p74_propro_p74
PMID: 15481153
IL-15 is particularly active on NK cells and strongly induces IFN-gamma release by this cell type.
c196 cso30:c:InputAssociation connector
c197 cso30:c:InputProcess connector
c198 cso30:c:OutputProcess connector
p75_propro_p75
PMID: 15481153
IFN-beta, IFIT1, and ISG15 belong to the primary response group.
c200 cso30:c:InputAssociation connector
c199 cso30:c:OutputProcess connector
p76_propro_p76
PMID: 15481153
IFN-beta, IFIT1, and ISG15 belong to the primary response group.
c202 cso30:c:InputAssociation connector
c201 cso30:c:OutputProcess connector
p77_propro_p77
PMID: 15481153
The secondary response group comprises interferon response genes, such as RF7, IRF9, and PKR.
c206 cso30:c:InputAssociation connector
c203 cso30:c:OutputProcess connector
p78_propro_p78
PMID: 15481153
The secondary response group comprises interferon response genes, such as RF7, IRF9, and PKR.
c207 cso30:c:InputAssociation connector
c204 cso30:c:OutputProcess connector
p79_propro_p79
PMID: 15481153
The secondary response group comprises interferon response genes, such as RF7, IRF9, and PKR.
c208 cso30:c:InputAssociation connector
c205 cso30:c:OutputProcess connector
p80_propro_p80
PMID: 15481153
Finally, IFN-beta is a type I interferon that induces Th1 differentiation in humans.
c209 cso30:c:InputAssociation connector
p81_propro_p81
PMID: 15481153
Stimulation with TLR4 agonist led to the production of IP-10, IFN-beta, MCP5, iNOS, and IL-12p40.
c211 cso30:c:InputAssociation connector
c210 cso30:c:OutputProcess connector
p82_propro_p82
PMID: 15481153
Stimulation with TLR4 agonist led to the production of IP-10, IFN-beta, MCP5, iNOS, and IL-12p40.
c213 cso30:c:InputAssociation connector
c212 cso30:c:OutputProcess connector
p84_propro_p84
PMID: 15481153, 12766768
In murine B cells, CpG DNA (TLR9 agonist), but not LPS, was found to induce the transcription factor T-bet and inhibit IgG1 and IgE switching induced by IL-4.
c217 cso30:c:InputAssociation connector
c216 cso30:c:OutputProcess connector
p85_propro_p85
PMID: 15481153
Moreover, the Th2 cytokines IL-4 and IL-5 were more abundantly released by mast cells stimulated through TLR2 than TLR4.
c220 cso30:c:InputAssociation connector
c218 cso30:c:OutputProcess connector
p86_propro_p86
PMID: 15481153
Moreover, the Th2 cytokines IL-4 and IL-5 were more abundantly released by mast cells stimulated through TLR2 than TLR4.
c221 cso30:c:InputAssociation connector
c219 cso30:c:OutputProcess connector
p87_propro_p87
PMID: 15481153
Moreover, the Th2 cytokines IL-4 and IL-5 were more abundantly released by mast cells stimulated through TLR2 than TLR4.
c224 cso30:c:InputAssociation connector
c222 cso30:c:OutputProcess connector
p88_propro_p88
PMID: 15481153
Moreover, the Th2 cytokines IL-4 and IL-5 were more abundantly released by mast cells stimulated through TLR2 than TLR4.
c225 cso30:c:InputAssociation connector
c223 cso30:c:OutputProcess connector
p89_propro_p89
PMID: 15481153
Preincubation with TLR2 agonist also blocked the induction of IP-10 by IFN-beta, suggesting that the mechanism of inhibition is not specific for TLR, or due to rapid tolerization, but rather is more proximal and restricted to the transcription of those genes.
c226 cso30:c:InputAssociation connector
c228 cso30:c:InputInhibitor connector
c227 cso30:c:OutputProcess connector
p90_propro_p90
PMID: 15481153, 12045249
Plasmacytoid cells respond by producing IFN-alpha, while myeloid DC preferentially express IL-12.
c233 cso30:c:InputAssociation connector
c255 cso30:c:InputAssociation connector
c232 cso30:c:OutputProcess connector
p91_propro_p91
PMID: 15481153, 12045249
Plasmacytoid cells respond by producing IFN-alpha, while myeloid DC preferentially express IL-12.
c254 cso30:c:InputAssociation connector
c234 cso30:c:OutputProcess connector
p92_propro_p92
PMID: 15481153, 14607893, 14579266, 12761116
The ability of TLR2 and TLR4 to induce distinct Th responses was confirmed in humans by in vitro Th cell differentiation experiments, and found to mirror the results obtained in mice, such that TLR2 agonists induced Th2 diffrentiation and TLR4 induced Th1.
c237 cso30:c:InputAssociation connector
p93_propro_p93
PMID: 15481153, 14607893, 14579266, 12761116
The ability of TLR2 and TLR4 to induce distinct Th responses was confirmed in humans by in vitro Th cell differentiation experiments, and found to mirror the results obtained in mice, such that TLR2 agonists induced Th2 diffrentiation and TLR4 induced Th1.
c238 cso30:c:InputAssociation connector
p94_propro_p94
PMID: 15481153, 12045249, 11812998
Similarly, TLR7 can induce IFN-alpha in human plasmacytoid DC (Ito et al., 2002) despite its inability to activate MyD88-independent signaling pathways.
c246 cso30:c:InputAssociation connector
c239 cso30:c:OutputProcess connector
p95_propro_p95
PMID: 15481153
For example, in human DC TLR3 is able to induce IP-10 and IL-15 to similar levels as TLR4, yet it induces IFN-beta only very weakly.
c242 cso30:c:InputAssociation connector
c241 cso30:c:OutputProcess connector
p96_propro_p96
PMID: 15481153, 11313410
DC maturation induced by LPS is a MyD88-independent response (Kaisho et al., 2001); however, it is also induced by TLR that cannot link to TRIF.
c243 cso30:c:InputAssociation connector
p97_propro_p97
PMID: 15481153, 12356687
For example, although both TLR2 and TLR9 exclusively activate the MyD88-dependent pathway, only TLR9 is able to induce IFN-beta production in mouse macrophages (Hoshino et al., 2002), thereby indicating the existence of differences between TLR2 and TLR9 that are not ascribable to the TRIF/IRF3 pathway.
c244 cso30:c:InputAssociation connector
c245 cso30:c:OutputProcess connector
p51_propro_p51
PMID: 15481153
TLR2 and TLR4 agonists were also equally capable of inducing DC maturation as measured by the up-regulation of several cell surface markers such as CD40, CD86, HLA-DR, and CD83.
c144 cso30:c:InputAssociation connector
c240 cso30:c:InputAssociation connector
c142 cso30:c:OutputProcess connector
p50_propro_p50
PMID: 15481153
TLR2 and TLR4 agonists were also equally capable of inducing DC maturation as measured by the up-regulation of several cell surface markers such as CD40, CD86, HLA-DR, and CD83.
c141 cso30:c:InputAssociation connector
c143 cso30:c:InputAssociation connector
c247 cso30:c:OutputProcess connector
p52_propro_p52
PMID: 15481153
TLR2 and TLR4 agonists were also equally capable of inducing DC maturation as measured by the up-regulation of several cell surface markers such as CD40, CD86, HLA-DR, and CD83.
c147 cso30:c:InputAssociation connector
c248 cso30:c:InputAssociation connector
c145 cso30:c:OutputProcess connector
p53_propro_p53
c148 cso30:c:InputAssociation connector
c249 cso30:c:InputAssociation connector
c146 cso30:c:OutputProcess connector
p54_propro_p54
c151 cso30:c:InputAssociation connector
c250 cso30:c:InputAssociation connector
c149 cso30:c:OutputProcess connector
p55_propro_p55
c152 cso30:c:InputAssociation connector
c251 cso30:c:InputAssociation connector
c150 cso30:c:OutputProcess connector
p56_propro_p56
c156 cso30:c:InputAssociation connector
c252 cso30:c:InputAssociation connector
c153 cso30:c:OutputProcess connector
p57_propro_p57
c155 cso30:c:InputAssociation connector
c253 cso30:c:InputAssociation connector
c154 cso30:c:OutputProcess connector
p98_propro_p98
PMID: 15481153
The fact that different TLR can induce such an array of responses suggest that they possess the ability to selectively activate distinct signaling pathways, which include the MAP kinases p38, c-Jun N-terminal kinase, ERK1/2, the transcription factors NF-kappaB and IRF-3, the PI3 kinase, and caspase-1.
c235 cso30:c:InputProcess connector
c256 cso30:c:InputAssociation connector
c236 cso30:c:OutputProcess connector
p99_propro_p99
PMID: 15481153
The fact that different TLR can induce such an array of responses suggest that they possess the ability to selectively activate distinct signaling pathways, which include the MAP kinases p38, c-Jun N-terminal kinase, ERK1/2, the transcription factors NF-kappaB and IRF-3, the PI3 kinase, and caspase-1.
c257 cso30:c:InputProcess connector
c259 cso30:c:InputAssociation connector
c258 cso30:c:OutputProcess connector
p100_propro_p100
PMID: 15481153
The fact that different TLR can induce such an array of responses suggest that they possess the ability to selectively activate distinct signaling pathways, which include the MAP kinases p38, c-Jun N-terminal kinase, ERK1/2, the transcription factors NF-kappaB and IRF-3, the PI3 kinase, and caspase-1.
c260 cso30:c:InputProcess connector
c262 cso30:c:InputAssociation connector
c261 cso30:c:OutputProcess connector
p83_propro_p83
PMID: 15481153
Stimulation with TLR4 agonist led to the production of IP-10, IFN-beta, MCP5, iNOS, and IL-12p40.
c215 cso30:c:InputAssociation connector
c263 cso30:c:InputAssociation connector
c214 cso30:c:OutputProcess connector
TLRs_enti_MO000019395
TLRs
TLR3_enti_MO000019398
TLR3
TLR5_enti_MO000019399
TLR5
TLR7_enti_MO000042126
TLR7
TLR8_enti_MO000042007
TLR8
TLR9_enti_MO000042012
TLR9
TLR11_enti_MO000042130
TLR11
MyD88_enti_MO000016573
MyD88
LPS_enti_MO000016882
LPS
dsRNA_enti_MO000022224
dsRNA
dsRNA:TLR3:TRIF_enti_MO000041437
dsRNA:TLR3:TRIF
dsRNA:TLR3_enti_MO000041446
dsRNA:TLR3
dsRNA:TLR3:TRIF:TBK1:IKK-i_enti_MO000041441
dsRNA:TLR3:TRIF:TBK1:IKK-i
flagellin_enti_MO000022185
flagellin
TLR1: TLR2_enti_e12
TLR1: TLR2
TLR2: TLR6_enti_e13
TLR2: TLR6
Lp_enti_MO000017793
Lp
TLR4_enti_MO000019394
TLR4
LPS: TLR4_enti_e14
LPS: TLR4
ligand_enti_e15
ligand
ligand: TLRs_enti_e16
ligand: TLRs
LPS: TLR4: MyD88_enti_e17
LPS: TLR4: MyD88
ligand: TLR: MyD88_enti_e18
ligand: TLR: MyD88
NF-kappaB_enti_MO000000058
NF-kappaB
IRAK-1_enti_MO000000213
IRAK-1
IRAK-4_enti_MO000039077
IRAK-4
ligand: TLR: MyD88: IRAK-1: IRAK-4_enti_e19
ligand: TLR: MyD88: IRAK-1: IRAK-4
TRAF6_enti_MO000000212
TRAF6
LPS: TLR4: MyD88: IRAK-1: IRAK-4_enti_e20
LPS: TLR4: MyD88: IRAK-1: IRAK-4
MAPKs_enti_MO000000077
MAPKs
IL-12 p40_enti_G010657
IL-12 p40
IL-12_enti_MO000017265
IL-12
IFN-gamma_enti_G010453
IFN-gamma
IFNgamma_enti_MO000016665
IFNgamma
IL-4_enti_G010469
IL-4
PGN_enti_MO000042032
PGN
CD40_enti_MO000016922
CD40
CD83_enti_MO000066711
CD83
CD86_enti_MO000017270
CD86
HLA-DRA_enti_MO000090613
HLA-DRA
Lp: TLR2: TLR6_enti_e21
Lp: TLR2: TLR6
PGN: TLR1: TLR2_enti_e22
PGN: TLR1: TLR2
TRIF_enti_MO000041125
TRIF
zymosan: TLR1: TLR2_enti_e23
zymosan: TLR1: TLR2
zymosan_enti_e24
zymosan
lipoarabinomanan_enti_e25
lipoarabinomanan
lipoarabinomanan: TLR1: TLR2_enti_e26
lipoarabinomanan: TLR1: TLR2
protein F_enti_e27
protein F
protein F: TLR4_enti_e28
protein F: TLR4
surfactant protein A_enti_e29
surfactant protein A
surfactant protein A: TLR4_enti_e30
surfactant protein A: TLR4
fibronectin fragments_enti_e31
fibronectin fragments
fibronectin fragments: TLR4_enti_e32
fibronectin fragments: TLR4
flagellin: TLR5_enti_e33
flagellin: TLR5
ssRNA_enti_e34
ssRNA
ssRNA: TLR7_enti_e35
ssRNA: TLR7
ssRNA: TLR8_enti_e36
ssRNA: TLR8
imidazoquinoline_enti_e37
imidazoquinoline
imidazoquinoline: TLR7_enti_e38
imidazoquinoline: TLR7
imidazoquinoline: TLR9_enti_e39
imidazoquinoline: TLR9
CpG DNA_enti_e40
CpG DNA
CpG DNA: TLR9_enti_e41
CpG DNA: TLR9
uropathogenic bacterial ligand_enti_e42
uropathogenic bacterial ligand
uropathogenic bacterial ligand: TLR11_enti_e43
uropathogenic bacterial ligand: TLR11
ligand: TLR: MyD88: IRAK-1: IRAK-4: TRAF6_enti_e44
ligand: TLR: MyD88: IRAK-1: IRAK-4: TRAF6
NF-kappaB{activated}_enti_e45
NF-kappaB{activated}
MAPKs{activated}_enti_e46
MAPKs{activated}
p38_enti_e47
p38
p38{activated}_enti_e48
p38{activated}
JNK_enti_e49
JNK
JNK{activated}_enti_e63
JNK{activated}
ERK1_enti_e64
ERK1
ERK1{activated}_enti_e65
ERK1{activated}
ERK2_enti_e66
ERK2
ERK2{activated}_enti_e67
ERK2{activated}
LPS: TLR4: MAL_enti_e68
LPS: TLR4: MAL
MAL_enti_e69
MAL
Lp: TLR2: TLR6: MAL_enti_e70
Lp: TLR2: TLR6: MAL
Lp: TLR2: TLR6: MAL: MyD88_enti_e71
Lp: TLR2: TLR6: MAL: MyD88
TRAM_enti_e72
TRAM
LPS: TLR4: TRAM_enti_e73
LPS: TLR4: TRAM
LPS: TLR4: TRAM: TRIF_enti_e74
LPS: TLR4: TRAM: TRIF
TBK1: IKK-i_enti_e75
TBK1: IKK-i
IRF-3_enti_e76
IRF-3
IRF-3[activated}_enti_e77
IRF-3[activated}
IFN-beta_enti_e78
IFN-beta
IP-10_enti_e79
IP-10
TLR4 agonist: TLR4_enti_e80
TLR4 agonist: TLR4
TLR2 agonist: TLR2_enti_e81
TLR2 agonist: TLR2
IL-12p70_enti_e82
IL-12p70
IL-15_enti_e83
IL-15
IL-8_enti_e84
IL-8
IL-10_enti_e85
IL-10
IL-23p19_enti_e86
IL-23p19
IL-12p70_enti_e87
IL-12p70
IL-12p40_enti_e88
IL-12p40
IL-12p40: IL-12p40_enti_e89
IL-12p40: IL-12p40
IL-12R_enti_e90
IL-12R
IL-12p40: IL-12p40: IL-12R_enti_e91
IL-12p40: IL-12p40: IL-12R
IL-12p19_enti_e92
IL-12p19
IL-12p40: IL-12p19_enti_e93
IL-12p40: IL-12p19
IL-12p35_enti_e94
IL-12p35
IFNgamma{extracellular}_enti_e95
IFNgamma{extracellular}
IP-10_enti_e96
IP-10
IL-15_enti_e97
IL-15
IFIT1_enti_e98
IFIT1
ISG-15_enti_e99
ISG-15
IRF-7_enti_e100
IRF-7
IRF-9_enti_e101
IRF-9
PKR_enti_e102
PKR
IFN-beta_enti_e103
IFN-beta
MCP-5_enti_e104
MCP-5
T-bet_enti_e106
T-bet
IL-5_enti_e107
IL-5
IFN-alpha_enti_e108
IFN-alpha
IFN-alpha_enti_e109
IFN-alpha
CD40_enti_G010691
CD40
CD86_enti_e111
CD86
CD83_enti_e112
CD83
HLA-DRA_enti_e113
HLA-DRA
PI3K_enti_e110
PI3K
PI3K{activated}_enti_e114
PI3K{activated}
caspase-1_enti_e115
caspase-1
caspase-1{activated}_enti_e116
caspase-1{activated}
i-NOS_enti_e105
i-NOS
i-NOS_enti_e117
i-NOS