_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e10
_enti_e4
_enti_e3
_enti_e2
_enti_e55
_enti_e59
_enti_e53
_enti_e54
_enti_e50
_enti_e56
_enti_e52
_enti_e51
_enti_e57
_enti_e58
_enti_e61
_enti_e62
_enti_e60
g1_fact_g1
g2_fact_g12
g2_fact_g13
g1_fact_g14
p1_propro_p1
PMID: 1757110, 3760571, 3108379
The fact that differences in TNF-o~ release could
be measured at the protein level within 4 h of addition
of priming/activating signals stimulated us to
begin looking at changes in expression of other early
response genes at the mRNA level, especially
those like c-fos, c-myc, JE and KC which are
known to be induced by LPS
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 1757110, 3760571, 3108379
The fact that differences in TNF-o~ release could
be measured at the protein level within 4 h of addition
of priming/activating signals stimulated us to
begin looking at changes in expression of other early
response genes at the mRNA level, especially
those like c-fos, c-myc, JE and KC which are
known to be induced by LPS
c4 cso30:c:InputAssociation connector
c5 cso30:c:OutputProcess connector
p2_propro_p3
PMID: 1757110, 3760571, 3108379
The fact that differences in TNF-o~ release could
be measured at the protein level within 4 h of addition
of priming/activating signals stimulated us to
begin looking at changes in expression of other early
response genes at the mRNA level, especially
those like c-fos, c-myc, JE and KC which are
known to be induced by LPS
c7 cso30:c:InputAssociation connector
c6 cso30:c:OutputProcess connector
p2_propro_p4
PMID: 1757110, 3760571, 3108379
The fact that differences in TNF-o~ release could
be measured at the protein level within 4 h of addition
of priming/activating signals stimulated us to
begin looking at changes in expression of other early
response genes at the mRNA level, especially
those like c-fos, c-myc, JE and KC which are
known to be induced by LPS
c8 cso30:c:InputAssociation connector
c9 cso30:c:OutputProcess connector
p2_propro_p5
PMID: 1757110, 3760571, 3108379
The fact that differences in TNF-o~ release could
be measured at the protein level within 4 h of addition
of priming/activating signals stimulated us to
begin looking at changes in expression of other early
response genes at the mRNA level, especially
those like c-fos, c-myc, JE and KC which are
known to be induced by LPS
PMID: 1757110
Priming with 33 units/ml interferon-3, along with
l0 ng/ml LPS induced much higher levels of KC
c10 cso30:c:InputAssociation connector
c15 cso30:c:InputAssociation connector
c11 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 1757110
Priming with 33 units/ml interferon-3, along with
l0 ng/ml LPS induced much higher levels of KC
c12 cso30:c:InputProcess connector
c13 cso30:c:InputProcess connector
c14 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 1757110
For c-fos, differences in
expression are observed within 20min following
stimulation with PMA plus ionophore. In this case,
however, resistant macrophages down-regulate expression
from a higher baseline level while susceptible
macrophages show enhanced expression over
the 20-min time course.
c16 cso30:c:InputAssociation connector
c17 cso30:c:InputAssociation connector
c18 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 1757110, 3497923, 2537468
Expression of both c-fos and c-jun is
stimulated by TNF-alpha.
c19 cso30:c:InputProcess connector
c20 cso30:c:InputProcess connector
c21 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 1757110, 3497923, 2537468
Expression of both c-fos and c-jun is
stimulated by TNF-alpha.
c22 cso30:c:InputAssociation connector
c23 cso30:c:OutputProcess connector
p9_propro_p10
PMID: 1757110, 3497923, 2537468
Expression of both c-fos and c-jun is
stimulated by TNF-alpha.
c24 cso30:c:InputAssociation connector
c25 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 1757110
In the case of c-fos, the
protein product for the gene dimerises with c-jun to
form the TRE binding protein complex AP-1, c-fos
itself having both TRE and CRE in its promoter region.
c26 cso30:c:InputAssociation connector
c27 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 1757110
In the case of c-fos, the
protein product for the gene dimerises with c-jun to
form the TRE binding protein complex AP-1, c-fos
itself having both TRE and CRE in its promoter region.
c30 cso30:c:InputProcess connector
c31 cso30:c:InputProcess connector
c32 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 1757110
In the case of c-fos, the
protein product for the gene dimerises with c-jun to
form the TRE binding protein complex AP-1, c-fos
itself having both TRE and CRE in its promoter region.
c28 cso30:c:InputAssociation connector
c29 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 1757110
TNF-o~ stimulates
prolonged expression at the mRNA level contrasting
with transient induction observed with the phorbol
ester TPA.
c33 cso30:c:InputAssociation connector
c34 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 1757110
This could involve differences in down regulation
of LPS or TNF-a receptors, or a cAMPdependent
down regulation of TNF-o~ production.
In preliminary experiments (T. I.A. Roach and
J.M. Blackwell, unpublished) we have established
that either addition of exogenous prostaglandin
E2, or inhibition of cAMP catabolism with theophylline,
reduces TNF-ot release.
c39 cso30:c:InputProcess connector
c38 cso30:c:InputInhibitor connector
c40 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 1757110, 3917283, 2112157
Previous studies have
shown, for example, that L. donovani is a potent
stimulator of prostaglandin E2 synthesis in BALB/
c (Lsh s) macrophages, and that preinfection of
macrophages selectively diminishes IL-1 (but not
TNF-ot) production.
c46 cso30:c:InputAssociation connector
c47 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 1757110, 3917283, 2112157
Previous studies have
shown, for example, that L. donovani is a potent
stimulator of prostaglandin E2 synthesis in BALB/
c (Lsh s) macrophages, and that preinfection of
macrophages selectively diminishes IL-1 (but not
TNF-ot) production.
c45 cso30:c:InputAssociation connector
c48 cso30:c:InputInhibitor connector
c44 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 1757110, 1707920
More recently, Descoteaux
and co-workers have shown that parasite-derived
lipophosphoglycan (LPG) stimulates rapid
expression of both c-fos and TNF-a genes
c51 cso30:c:InputAssociation connector
c50 cso30:c:OutputProcess connector
p20_propro_p21
PMID: 1757110, 1707920
More recently, Descoteaux
and co-workers have shown that parasite-derived
lipophosphoglycan (LPG) stimulates rapid
expression of both c-fos and TNF-a genes
c49 cso30:c:InputAssociation connector
c52 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 1757110
LPG induced a rapid
down-modulation of TNF-a receptors but did not
impair stimulation of expression of c-fos by the
cAMP analogue, dibutyryl cAMP.
c53 cso30:c:InputInhibitor connector
c54 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 1757110
LPG induced a rapid
down-modulation of TNF-a receptors but did not
impair stimulation of expression of c-fos by the
cAMP analogue, dibutyryl cAMP.
c55 cso30:c:InputAssociation connector
c56 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 1757110
LPG induced a rapid
down-modulation of TNF-a receptors but did not
impair stimulation of expression of c-fos by the
cAMP analogue, dibutyryl cAMP.
c57 cso30:c:InputAssociation connector
c58 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 1757110, 2999236
The LPS itself acts as a potent stimulator of TNF-ct
release, which may then form an autocrine
loop acting back on the macrophage.
PMID: 1757110
This could involve differences in down regulation
of LPS or TNF-a receptors, or a cAMPdependent
down regulation of TNF-o~ production.
In preliminary experiments (T. I.A. Roach and
J.M. Blackwell, unpublished) we have established
that either addition of exogenous prostaglandin
E2, or inhibition of cAMP catabolism with theophylline,
reduces TNF-ot release.
c64 cso30:c:InputAssociation connector
c66 cso30:c:InputAssociation connector
c68 cso30:c:InputInhibitor connector
c91 cso30:c:InputInhibitor connector
c65 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 1757110, 3745439, 2451695, 2497225
NO mediates L-arginine dependent tumour cyo
tostasis during co-culture with interferon-7 and
LPS activated macrophages, possibly via nitrosylation
reactions which remove labile iron atoms from
Fe-S prosthetic groups of aconitase and complexes
I and II of the mitochondrial electron transport
system
c61 cso30:c:InputAssociation connector
c62 cso30:c:InputProcess connector
c63 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 1757110, 2279740, 2175327
In the context of the L. major model, Liew and
co-workers have shown that, in the presence
of 10ng/ml LPS, recombinant TNF-et acts
synergistically with interferon-3, to give maximal
production of INO and antileishmanial activity.
PMID: 1757110, 2999236
This was confirmed
by Green and co-workers [47] who showed
that neutralizing anti-TNF-a antibodies blocked
production of INO and antileishmanial activity in
interferon-3, primed peritoneal macrophages.
PMID: 1757110, 1712077, 2432665, 3242600
In this system,
L-arginine is oxidised by an inducible NADPHdependent
enzyme (NO synthase) to yield L-citrulline,
nitrite and nitrate, with highly reactive nitric
oxide (NO) produced as an intermediate.
The
degree of kill correlated well with the levels of nitrites
measured in the supernatants at 72 h, and
inclusion of 200 #M L-NMMA, a competitive inhibitor
of the L-arginine dependent pathway for the
synthesis of INO, inhibited the killing
c75 cso30:c:InputProcess connector
c77 cso30:c:InputAssociation connector
c78 cso30:c:InputAssociation connector
c79 cso30:c:InputInhibitor connector
c94 cso30:c:InputInhibitor connector
c76 cso30:c:OutputProcess connector
p30_propro_p30
PMID:1757110
In
this case, the parasite (L. major) itself acted as the
stimulus for TNF-a release by the macrophage.
PMID: 1757110
This could involve differences in down regulation
of LPS or TNF-a receptors, or a cAMPdependent
down regulation of TNF-o~ production.
In preliminary experiments (T. I.A. Roach and
J.M. Blackwell, unpublished) we have established
that either addition of exogenous prostaglandin
E2, or inhibition of cAMP catabolism with theophylline,
reduces TNF-ot release.
c80 cso30:c:InputAssociation connector
c82 cso30:c:InputAssociation connector
c67 cso30:c:InputInhibitor connector
c90 cso30:c:InputInhibitor connector
c81 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 1757110
The magnitude
of this response was enhanced in macrophages preinfected
with L. donovani amastigotes, suggesting
again that the parasite itself may act as a trigger for
TNF-ct production/release.
PMID: 1757110
This could involve differences in down regulation
of LPS or TNF-a receptors, or a cAMPdependent
down regulation of TNF-o~ production.
In preliminary experiments (T. I.A. Roach and
J.M. Blackwell, unpublished) we have established
that either addition of exogenous prostaglandin
E2, or inhibition of cAMP catabolism with theophylline,
reduces TNF-ot release.
c83 cso30:c:InputAssociation connector
c85 cso30:c:InputAssociation connector
c69 cso30:c:InputInhibitor connector
c71 cso30:c:InputInhibitor connector
c84 cso30:c:OutputProcess connector
p32_propro_p32
PMID: 1757110, 1712077, 2432665, 3242600
In this system,
L-arginine is oxidised by an inducible NADPHdependent
enzyme (NO synthase) to yield L-citrulline,
nitrite and nitrate, with highly reactive nitric
oxide (NO) produced as an intermediate.
c86 cso30:c:InputAssociation connector
c87 cso30:c:OutputProcess connector
c88 cso30:c:OutputProcess connector
c89 cso30:c:OutputProcess connector
p29_propro_p15
PMID: 1757110, 2279740, 2175327
In the context of the L. major model, Liew and
co-workers have shown that, in the presence
of 10ng/ml LPS, recombinant TNF-et acts
synergistically with interferon-3, to give maximal
production of INO and antileishmanial activity.
PMID: 1757110, 2999236
This was confirmed
by Green and co-workers [47] who showed
that neutralizing anti-TNF-a antibodies blocked
production of INO and antileishmanial activity in
interferon-3, primed peritoneal macrophages.
PMID: 1757110, 1712077, 2432665, 3242600
In this system,
L-arginine is oxidised by an inducible NADPHdependent
enzyme (NO synthase) to yield L-citrulline,
nitrite and nitrate, with highly reactive nitric
oxide (NO) produced as an intermediate.
The
degree of kill correlated well with the levels of nitrites
measured in the supernatants at 72 h, and
inclusion of 200 #M L-NMMA, a competitive inhibitor
of the L-arginine dependent pathway for the
synthesis of INO, inhibited the killing
c35 cso30:c:InputAssociation connector
c37 cso30:c:InputProcess connector
c73 cso30:c:InputAssociation connector
c92 cso30:c:InputInhibitor connector
c95 cso30:c:InputInhibitor connector
c41 cso30:c:OutputProcess connector
p29_propro_p17
PMID: 1757110, 2279740, 2175327
In the context of the L. major model, Liew and
co-workers have shown that, in the presence
of 10ng/ml LPS, recombinant TNF-et acts
synergistically with interferon-3, to give maximal
production of INO and antileishmanial activity.
PMID: 1757110, 2999236
This was confirmed
by Green and co-workers [47] who showed
that neutralizing anti-TNF-a antibodies blocked
production of INO and antileishmanial activity in
interferon-3, primed peritoneal macrophages.
PMID: 1757110, 1712077, 2432665, 3242600
In this system,
L-arginine is oxidised by an inducible NADPHdependent
enzyme (NO synthase) to yield L-citrulline,
nitrite and nitrate, with highly reactive nitric
oxide (NO) produced as an intermediate.
The
degree of kill correlated well with the levels of nitrites
measured in the supernatants at 72 h, and
inclusion of 200 #M L-NMMA, a competitive inhibitor
of the L-arginine dependent pathway for the
synthesis of INO, inhibited the killing
c36 cso30:c:InputAssociation connector
c42 cso30:c:InputProcess connector
c74 cso30:c:InputAssociation connector
c93 cso30:c:InputInhibitor connector
c96 cso30:c:InputInhibitor connector
c43 cso30:c:OutputProcess connector
LPS_enti_MO000016882
LPS
TLR4_enti_MO000019394
TLR4
LPS:TLR4_enti_e5
LPS:TLR4
c-fos_enti_G010214
c-fos
c-myc_enti_G010239
c-myc
JE_enti_e6
JE
KC_enti_e11
KC
IFNgamma_enti_MO000016665
IFNgamma
IFNgamma R_enti_e12
IFNgamma R
IFNgamma:R_enti_e13
IFNgamma:R
PMA_enti_e14
PMA
ionophore_enti_e15
ionophore
TNF-alpha_enti_MO000000289
TNF-alpha
TNF-alpha:receptor_enti_e16
TNF-alpha:receptor
TNF-alpha receptor_enti_e17
TNF-alpha receptor
c-Jun_enti_MO000000049
c-Jun
c-jun_enti_G010232
c-jun
c-Fos_enti_MO000000279
c-Fos
c-Jun:c-Fos(AP-1)_enti_MO000055986
c-Jun:c-Fos(AP-1)
Phorbol ester TPA_enti_e18
Phorbol ester TPA
cAMP_enti_e19
cAMP
TNF-alpha_enti_G010329
TNF-alpha
PGE2(exogenous)_enti_e20
PGE2(exogenous)
Theophylline_enti_e21
Theophylline
AMP_enti_e22
AMP
L.donovani_enti_e23
L.donovani
PGE2_enti_e24
PGE2
IL-1_enti_MO000000214
IL-1
Il-1_enti_e25
Il-1
LPG_enti_e26
LPG
TNFAR_enti_e27
TNFAR
Dibutyryl cAMP_enti_e28
Dibutyryl cAMP
NO_enti_e29
NO
L-arginine_enti_e30
L-arginine
NO synthase_enti_e31
NO synthase
L-citrulline_enti_e33
L-citrulline
nitrite_enti_e32
nitrite
nitrate_enti_e34
nitrate
aconitate hydratase_enti_MO000088573
aconitate hydratase
Labile Iron atoms_enti_e35
Fe
Labile Iron atoms
L-NMMA_enti_e36
L-NMMA
neutralizing anti TNF-alpha antibody_enti_e37
neutralizing anti TNF-alpha antibody
L.major_enti_e38
L.major