_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e10
_enti_e4
_enti_e3
_enti_e2
_enti_e55
_enti_e59
_enti_e53
_enti_e51
_enti_e56
_enti_e54
_enti_e52
_enti_e50
_enti_e58
_enti_e61
_enti_e57
_enti_e62
_enti_e60
g1_fact_g1
g2_fact_g12
g2_fact_g13
g1_fact_g14
p1_propro_p1
PMID:15967158,15051069
For example, PAMPs produced by cellwall components of Gram-negative
bacteria (LPS) are recognized by TLR4; it involves the binding of LPS to a serum protein,
lipopolysaccharide-binding protein (LPB), which in turn binds to membrane CD14, which
transfers the complex to TLR4 in an MD-2-dependent manner
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p2_propro_p2
PMID:15967158,15051069
For example, PAMPs produced by cellwall components of Gram-negative
bacteria (LPS) are recognized by TLR4; it involves the binding of LPS to a serum protein,
lipopolysaccharide-binding protein (LPB), which in turn binds to membrane CD14, which
transfers the complex to TLR4 in an MD-2-dependent manner
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c6 cso30:c:OutputProcess connector
p2_propro_p3
PMID:15967158,15051069
For example, PAMPs produced by cellwall components of Gram-negative
bacteria (LPS) are recognized by TLR4; it involves the binding of LPS to a serum protein,
lipopolysaccharide-binding protein (LPB), which in turn binds to membrane CD14, which
transfers the complex to TLR4 in an MD-2-dependent manner
c7 cso30:c:InputProcess connector
c8 cso30:c:InputProcess connector
c9 cso30:c:OutputProcess connector
p2_propro_p4
PMID:15967158,15051069
For example, PAMPs produced by cellwall components of Gram-negative
bacteria (LPS) are recognized by TLR4; it involves the binding of LPS to a serum protein,
lipopolysaccharide-binding protein (LPB), which in turn binds to membrane CD14, which
transfers the complex to TLR4 in an MD-2-dependent manner
c10 cso30:c:InputProcess connector
c11 cso30:c:InputProcess connector
c12 cso30:c:OutputProcess connector
c64 cso30:c:OutputProcess connector
c65 cso30:c:OutputProcess connector
p5_propro_p5
PMID:15967158
They are then released into
the bloodstream and transported to sites in or close to the POA that react to their stimulation
by selectively expressing COX-2 and mPGES-1.
c26 cso30:c:InputAssociation connector
c30 cso30:c:OutputProcess connector
p6_propro_p6
PMID:15967158
They are then released into
the bloodstream and transported to sites in or close to the POA that react to their stimulation
by selectively expressing COX-2 and mPGES-1.
c13 cso30:c:InputProcess connector
c14 cso30:c:InputProcess connector
c15 cso30:c:OutputProcess connector
p5_propro_p7
PMID:15967158
They are then released into
the bloodstream and transported to sites in or close to the POA that react to their stimulation
by selectively expressing COX-2 and mPGES-1.
c25 cso30:c:InputAssociation connector
c29 cso30:c:OutputProcess connector
p6_propro_p8
PMID:15967158
They are then released into
the bloodstream and transported to sites in or close to the POA that react to their stimulation
by selectively expressing COX-2 and mPGES-1.
c16 cso30:c:InputProcess connector
c17 cso30:c:InputProcess connector
c18 cso30:c:OutputProcess connector
p6_propro_p9
PMID:15967158
They are then released into
the bloodstream and transported to sites in or close to the POA that react to their stimulation
by selectively expressing COX-2 and mPGES-1.
c19 cso30:c:InputProcess connector
c20 cso30:c:InputProcess connector
c21 cso30:c:OutputProcess connector
p6_propro_p10
PMID:15967158
They are then released into
the bloodstream and transported to sites in or close to the POA that react to their stimulation
by selectively expressing COX-2 and mPGES-1.
c22 cso30:c:InputProcess connector
c23 cso30:c:InputProcess connector
c24 cso30:c:OutputProcess connector
p5_propro_p11
PMID:15967158
They are then released into
the bloodstream and transported to sites in or close to the POA that react to their stimulation
by selectively expressing COX-2 and mPGES-1.
c27 cso30:c:InputAssociation connector
c31 cso30:c:OutputProcess connector
p5_propro_p12
PMID:15967158
They are then released into
the bloodstream and transported to sites in or close to the POA that react to their stimulation
by selectively expressing COX-2 and mPGES-1.
c28 cso30:c:InputAssociation connector
c32 cso30:c:OutputProcess connector
p5_propro_p13
PMID:15967158
They are then released into
the bloodstream and transported to sites in or close to the POA that react to their stimulation
by selectively expressing COX-2 and mPGES-1.
c33 cso30:c:InputAssociation connector
c37 cso30:c:OutputProcess connector
p5_propro_p14
PMID:15967158
They are then released into
the bloodstream and transported to sites in or close to the POA that react to their stimulation
by selectively expressing COX-2 and mPGES-1.
c34 cso30:c:InputAssociation connector
c38 cso30:c:OutputProcess connector
p5_propro_p15
PMID:15967158
They are then released into
the bloodstream and transported to sites in or close to the POA that react to their stimulation
by selectively expressing COX-2 and mPGES-1.
c35 cso30:c:InputAssociation connector
c39 cso30:c:OutputProcess connector
p5_propro_p16
PMID:15967158
They are then released into
the bloodstream and transported to sites in or close to the POA that react to their stimulation
by selectively expressing COX-2 and mPGES-1.
c36 cso30:c:InputAssociation connector
c40 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 15967158,9748570,9880592,12957837,9917869,10578230
In support, LPS,
like IL-1beta, induces these enzymes in endothelial cells of the cerebral microvasculature,
including in the OVLT, the choroid plexi and the leptomeninges
c41 cso30:c:InputAssociation connector
c42 cso30:c:OutputProcess connector
p17_propro_p18
PMID: 15967158,9748570,9880592,12957837,9917869,10578230
In support, LPS,
like IL-1beta, induces these enzymes in endothelial cells of the cerebral microvasculature,
including in the OVLT, the choroid plexi and the leptomeninges
c43 cso30:c:InputAssociation connector
c44 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 15967158,8027674,12376404,14977603
Indeed, the activation by LPS of group IV cytosolic
phospholipase (cPL)A2 is significantly delayed in vitro and in vivo
c45 cso30:c:InputAssociation connector
c46 cso30:c:InputProcess connector
c47 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 15967158,7664696,8193936
the expression
of c-fos in the nucleus of the solitary tract (NTS, the primary projection area of the vagus
nerves) is enhanced after i.v. and i.p. IL-1beta and i.v. LPS
c48 cso30:c:InputAssociation connector
c49 cso30:c:OutputProcess connector
p20_propro_p21
PMID: 15967158,7664696,8193936
the expression
of c-fos in the nucleus of the solitary tract (NTS, the primary projection area of the vagus
nerves) is enhanced after i.v. and i.p. IL-1beta and i.v. LPS
c50 cso30:c:InputAssociation connector
c51 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 15967158
Together, these data, plus
others not described, thus substantiate the notion that circulating LPS arriving in the liver
could activate Kc to produce and release TNFalpha, IL-1beta and IL-6
c52 cso30:c:InputAssociation connector
c53 cso30:c:OutputProcess connector
p22_propro_p23
PMID: 15967158
Together, these data, plus
others not described, thus substantiate the notion that circulating LPS arriving in the liver
could activate Kc to produce and release TNFalpha, IL-1beta and IL-6
c55 cso30:c:InputAssociation connector
c56 cso30:c:OutputProcess connector
p22_propro_p24
PMID: 15967158
Together, these data, plus
others not described, thus substantiate the notion that circulating LPS arriving in the liver
could activate Kc to produce and release TNFalpha, IL-1beta and IL-6
c54 cso30:c:InputAssociation connector
c57 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 15967158
Together, these data, plus
others not described, thus substantiate the notion that circulating LPS arriving in the liver
could activate Kc to produce and release TNFalpha, IL-1beta and IL-6
c58 cso30:c:InputAssociation connector
c59 cso30:c:OutputProcess connector
p25_propro_p26
PMID: 15967158
Together, these data, plus
others not described, thus substantiate the notion that circulating LPS arriving in the liver
could activate Kc to produce and release TNFalpha, IL-1beta and IL-6
c60 cso30:c:InputAssociation connector
c61 cso30:c:OutputProcess connector
p25_propro_p27
PMID: 15967158
Together, these data, plus
others not described, thus substantiate the notion that circulating LPS arriving in the liver
could activate Kc to produce and release TNFalpha, IL-1beta and IL-6
c62 cso30:c:InputAssociation connector
c63 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 15967158
Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via
the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of
surface-bound and fluid-phase C3b and iC3b
c66 cso30:c:InputAssociation connector
c67 cso30:c:OutputProcess connector
p28_propro_p29
PMID: 15967158
Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via
the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of
surface-bound and fluid-phase C3b and iC3b
c68 cso30:c:InputAssociation connector
c69 cso30:c:OutputProcess connector
p28_propro_p30
PMID: 15967158
Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via
the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of
surface-bound and fluid-phase C3b and iC3b
c70 cso30:c:InputAssociation connector
c71 cso30:c:OutputProcess connector
p28_propro_p31
PMID: 15967158
Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via
the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of
surface-bound and fluid-phase C3b and iC3b
c72 cso30:c:InputAssociation connector
c74 cso30:c:OutputProcess connector
p28_propro_p32
PMID: 15967158
Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via
the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of
surface-bound and fluid-phase C3b and iC3b
c73 cso30:c:InputAssociation connector
c75 cso30:c:OutputProcess connector
p28_propro_p33
PMID: 15967158
Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via
the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of
surface-bound and fluid-phase C3b and iC3b
c76 cso30:c:InputAssociation connector
c78 cso30:c:OutputProcess connector
p28_propro_p34
PMID: 15967158
Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via
the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of
surface-bound and fluid-phase C3b and iC3b
c77 cso30:c:InputAssociation connector
c79 cso30:c:OutputProcess connector
p35_propro_p35
PMID: 15967158
PGE2, under these conditions, could be generated via the
hydrolysis of membrane-associated phosphoinositide (PI, which has a high arachydonoyl
chain content) by PI-specific phospholipase C (PI-PLC)
PMID: 15967158,5284360
Vane demonstrated that aspirin blocks prostaglandin synthesis
c80 cso30:c:InputProcess connector
c82 cso30:c:InputAssociation connector
c111 cso30:c:InputInhibitor connector
c81 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 15967158
indeed, arachidonic acid (AA)
liberation by PI-PLC is 10-fold more rapid (within seconds) than that mediated by cPLA2
PMID: 15967158
Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the
subsequent conversion of this AA to PGE2 is catalyzed by COX-1
c83 cso30:c:InputAssociation connector
c84 cso30:c:OutputProcess connector
p36_propro_p37
PMID: 15967158,
indeed, arachidonic acid (AA)
liberation by PI-PLC is 10-fold more rapid (within seconds) than that mediated by cPLA2
c85 cso30:c:InputAssociation connector
c86 cso30:c:OutputProcess connector
p38_propro_p38
PMID: 15967158
Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the
subsequent conversion of this AA to PGE2 is catalyzed by COX-1
c87 cso30:c:InputAssociation connector
c88 cso30:c:InputProcess connector
c89 cso30:c:OutputProcess connector
p38_propro_p39
PMID: 15967158
Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the
subsequent conversion of this AA to PGE2 is catalyzed by COX-1
c90 cso30:c:InputAssociation connector
c91 cso30:c:InputProcess connector
c92 cso30:c:OutputProcess connector
p38_propro_p40
PMID: 15967158
Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the
subsequent conversion of this AA to PGE2 is catalyzed by COX-1
c93 cso30:c:InputAssociation connector
c94 cso30:c:InputProcess connector
c95 cso30:c:OutputProcess connector
p38_propro_p41
PMID: 15967158
Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the
subsequent conversion of this AA to PGE2 is catalyzed by COX-1
c96 cso30:c:InputAssociation connector
c97 cso30:c:InputProcess connector
c98 cso30:c:OutputProcess connector
p38_propro_p42
PMID: 15967158
Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the
subsequent conversion of this AA to PGE2 is catalyzed by COX-1
c99 cso30:c:InputAssociation connector
c100 cso30:c:InputProcess connector
c101 cso30:c:OutputProcess connector
p38_propro_p43
PMID: 15967158
Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the
subsequent conversion of this AA to PGE2 is catalyzed by COX-1
c102 cso30:c:InputAssociation connector
c103 cso30:c:InputProcess connector
c104 cso30:c:OutputProcess connector
p38_propro_p44
PMID: 15967158
Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the
subsequent conversion of this AA to PGE2 is catalyzed by COX-1
c105 cso30:c:InputAssociation connector
c106 cso30:c:InputProcess connector
c107 cso30:c:OutputProcess connector
p45_propro_p45
PMID: 15967158
Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the
subsequent conversion of this AA to PGE2 is catalyzed by COX-1
PMID: 15967158,5284360
Vane demonstrated that aspirin blocks prostaglandin synthesis
c108 cso30:c:InputAssociation connector
c110 cso30:c:InputAssociation connector
c112 cso30:c:InputInhibitor connector
c109 cso30:c:OutputProcess connector
p46_propro_p46
PMID: 15967158,11113021,11113018
Thus, it is now generally believed that cyclooxygenase (COX)-2 and microsomal
prostaglandin E synthase (mPGES)-1 selectively induced by pyrogenic cytokines
catalyze its production, and that it acts in the preoptic-anterior hypothalamus (POA), the
brain site of the primary thermoregulatory controller
PMID: 15967158
The second step of
the conventional sequence asserts that the synthesis of PGE2 is effected in the POA via
catalysis by COX-2 and mPGES-1
PMID: 15967158,5284360
Vane demonstrated that aspirin blocks prostaglandin synthesis
c113 cso30:c:InputAssociation connector
c122 cso30:c:InputInhibitor connector
c114 cso30:c:OutputProcess connector
p46_propro_p47
PMID: 15967158,11113021,11113018
Thus, it is now generally believed that cyclooxygenase (COX)-2 and microsomal
prostaglandin E synthase (mPGES)-1 selectively induced by pyrogenic cytokines
catalyze its production, and that it acts in the preoptic-anterior hypothalamus (POA), the
brain site of the primary thermoregulatory controller
PMID: 15967158
The second step of
the conventional sequence asserts that the synthesis of PGE2 is effected in the POA via
catalysis by COX-2 and mPGES-1
PMID: 15967158,5284360
Vane demonstrated that aspirin blocks prostaglandin synthesis
c115 cso30:c:InputAssociation connector
c121 cso30:c:InputInhibitor connector
c116 cso30:c:OutputProcess connector
p48_propro_p48
PMID: 15967158,9453538,1570314,7631045,10223523
Moreover, the transcription and translation of inducible COX-2 and mPGES-1 by
inflammatory stimuli, LPS and IL-1beta alike, require at least 1 h in vitro
c117 cso30:c:InputAssociation connector
c118 cso30:c:OutputProcess connector
p48_propro_p49
PMID: 15967158,9453538,1570314,7631045,10223523
Moreover, the transcription and translation of inducible COX-2 and mPGES-1 by
inflammatory stimuli, LPS and IL-1beta alike, require at least 1 h in vitro
c119 cso30:c:InputAssociation connector
c120 cso30:c:OutputProcess connector
p50_propro_p50
PMID: 15967158,14977603,15492017,11262580,15353338,15373964
the
consensus has now developed that the febrile response to LPS (and also to live bacteria
is probably not initiated by newly generated, blood-borne pyrogenic cytokines,
but rather by the production of PGE2 directly stimulated in the periphery by the exogenous
pyrogens themselves
PMID: 15967158,5284360
Vane demonstrated that aspirin blocks prostaglandin synthesis
c123 cso30:c:InputAssociation connector
c125 cso30:c:InputInhibitor connector
c124 cso30:c:OutputProcess connector
p51_propro_p51
PMID: 15967158
In conscious guinea pigs, Tc and plasma PGE2 rise simultaneously and concurrently with
the first appearance in Kc of i.v. or i.p. injected LPS.
PMID: 15967158,9100920,9608013,10600909
The associated Kc uptake of i.v. or i.p. LPS, the rise in plasma PGE2 and the febrile
response are prevented by pre-treatment with gadolinium chloride, an agent that temporarily
depletes Kc, or with CVF, a decomplementing toxin
PMID: 15967158
Pre-treatment with PGE2 anti-serum (which does not cross
the BBB) reduces the rises in Tc and plasma and preoptic PGE2 induced by i.v. LPS
in conscious guinea pigs
c126 cso30:c:InputAssociation connector
c128 cso30:c:InputInhibitor connector
c129 cso30:c:InputInhibitor connector
c130 cso30:c:InputInhibitor connector
c127 cso30:c:OutputProcess connector
p52_propro_p52
PMID: 15967158
The addition of serum C alone or in combination with LPS, but
not of LPS alone, to primary Kc from guinea pigs and mice in vitro provokes the virtually
immediate, near-maximal release of PGE2 by these cells; this response is catalyzed nondifferentially
by COX-1 and COX-2 (constitutive in Kc).
c131 cso30:c:InputAssociation connector
c134 cso30:c:InputAssociation connector
c151 cso30:c:InputInhibitor connector
c132 cso30:c:OutputProcess connector
p52_propro_p53
PMID: 15967158
The addition of serum C alone or in combination with LPS, but
not of LPS alone, to primary Kc from guinea pigs and mice in vitro provokes the virtually
immediate, near-maximal release of PGE2 by these cells; this response is catalyzed nondifferentially
by COX-1 and COX-2 (constitutive in Kc).
c133 cso30:c:InputAssociation connector
c135 cso30:c:InputAssociation connector
c152 cso30:c:InputInhibitor connector
c136 cso30:c:OutputProcess connector
p52_propro_p54
PMID: 15967158
The addition of serum C alone or in combination with LPS, but
not of LPS alone, to primary Kc from guinea pigs and mice in vitro provokes the virtually
immediate, near-maximal release of PGE2 by these cells; this response is catalyzed nondifferentially
by COX-1 and COX-2 (constitutive in Kc).
c137 cso30:c:InputAssociation connector
c138 cso30:c:InputAssociation connector
c139 cso30:c:InputAssociation connector
c150 cso30:c:InputInhibitor connector
c140 cso30:c:OutputProcess connector
p52_propro_p55
PMID: 15967158
The addition of serum C alone or in combination with LPS, but
not of LPS alone, to primary Kc from guinea pigs and mice in vitro provokes the virtually
immediate, near-maximal release of PGE2 by these cells; this response is catalyzed nondifferentially
by COX-1 and COX-2 (constitutive in Kc).
c141 cso30:c:InputAssociation connector
c142 cso30:c:InputAssociation connector
c143 cso30:c:InputAssociation connector
c153 cso30:c:InputInhibitor connector
c144 cso30:c:OutputProcess connector
p56_propro_p56
PMID: 15967158,4145320
NE also stimulates the release of PGE2 in brain tissue in vitro
c145 cso30:c:InputProcess connector
c146 cso30:c:InputProcess connector
c147 cso30:c:OutputProcess connector
p57_propro_p57
PMID: 15967158,4145320
NE also stimulates the release of PGE2 in brain tissue in vitro
PMID: 15967158,5284360
Vane demonstrated that aspirin blocks prostaglandin synthesis
c148 cso30:c:InputAssociation connector
c149 cso30:c:OutputProcess connector
LPS_enti_MO000016882
LPS
LPS:LBP:CD14_enti_MO000021929
LPS:LBP:CD14
LPS:LBP_enti_MO000021928
LPS:LBP
CD14_enti_MO000018132
CD14
LBP_enti_MO000019420
LBP
TLR4_enti_MO000019394
TLR4
MD-2_enti_MO000022131
MD-2
TLR4-MD-2_enti_e5
TLR4-MD-2
TLR4:LPS_enti_e6
TLR4:LPS
TNF-alpha_enti_G010329
TNF-alpha
IL-6_enti_G010262
IL-6
IL-1beta_enti_G010389
IL-1beta
IFNgamma_enti_MO000016665
IFNgamma
TNF-alpha_enti_MO000000289
TNF-alpha
IL-6_enti_MO000007384
IL-6
IL-6R_enti_MO000018458
IL-6R
Il-1:IL-6R_enti_e11
Il-1:IL-6R
IL-1beta_enti_MO000016597
IL-1beta
IL-1beta R_enti_e12
IL-1beta R
IL-1beta:IL-1betaR_enti_e13
IL-1beta:IL-1betaR
TNF-alphaR_enti_e14
TNF-alphaR
TNF-alpha:TNF-alphaR_enti_e15
TNF-alpha:TNF-alphaR
IFN-gammaR_enti_e16
IFN-gammaR
IFN-gamma:IFN-gammaR_enti_e17
IFN-gamma:IFN-gammaR
Cox-2_enti_e18
Cox-2
mPGES-1_enti_e19
mPGES-1
cPLA2_enti_e20
cPLA2
cPLA2{active}_enti_e21
cPLA2{active}
c-fos_enti_G010214
c-fos
C4A_enti_MO000069831
C4A
C3a_enti_MO000034980
C3a
C5a_enti_MO000033607
C5a
C3b_enti_e22
C3b
iC3b_enti_e23
iC3b
C3b_enti_e24
C3b
iC3b_enti_e25
iC3b
PGE2_enti_MO000021939
PGE2
Phosphoinositide_enti_e26
Phosphoinositide
PI-PLC{active}_enti_e27
PI-PLC{active}
Arachidonic acid_enti_e28
Arachidonic acid
PI-PLC_enti_e29
PI-PLC
COX-1_enti_MO000018979
COX-1
Aspirin_enti_e30
Aspirin
COX-2_enti_MO000017266
COX-2
mPGES-1_enti_e31
mPGES-1
pyrogens_enti_e32
pyrogens
Gadolinium chloride_enti_e33
Gadolinium chloride
CVF_enti_e34
CVF
PGE2 anti serum_enti_e35
PGE2 anti serum
serum c_enti_e36
serum c
NE_enti_e37
NE
NE receptor_enti_e38
NE receptor
NE:receptor_enti_e39
NE:receptor