Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262
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ABSTRACT |
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The transcriptional regulatory
factor nuclear factor (NF)-B has a central role in modulating
expression of proinflammatory mediators that are important in acute
lung injury. In vitro studies have shown that competition between
NF-
B and cAMP response element binding protein (CREB) for binding to
the coactivator CREB-binding protein (CBP) is important in regulating
transcriptional activity of these factors. In the present study, we
examined in vivo interactions between CBP, CREB, and NF-
B in
hemorrhage- or endotoxemia-induced acute lung injury. Association of
CBP with CREB or the p65 subunit of NF-
B increased in the lungs
after hemorrhage or endotoxemia. Inhibition of xanthine oxidase before
hemorrhage, but not before endotoxemia, decreased p65-CBP interactions
while increasing those between CREB and CBP. These alterations in
CREB-CBP and p65-CBP interactions were functionally significant because
xanthine oxidase inhibition before hemorrhage resulted in increased
expression of the CREB-dependent gene c-Fos and decreased expression of
macrophage inflammatory protein-2, a NF-
B-dependent gene. The
present results show that the coactivator CBP has an important role in
modulating transcription in vivo under clinically relevant
pathophysiological conditions.
acute lung injury; inflammation; gene expression regulation; transcription factors; reactive oxygen species; adenosine 3'5'-cyclic
monophosphate response element binding protein binding protein; nuclear
factor-B
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INTRODUCTION |
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ACUTE LUNG INJURY OCCURS
FREQUENTLY after severe infection or blood loss
(27). Pulmonary findings characteristic of acute lung
injury include massive accumulation of neutrophils (8, 18), increased proinflammatory cytokine levels (14, 15, 32a), and release of reactive oxygen intermediates (ROIs)
(34). Interleukin (IL)-1, tumor necrosis factor
(TNF)-
, and macrophage inflammatory protein (MIP)-2 are increased in
the lung after hemorrhage or endotoxemia and contribute to lung
inflammation and injury (31). Binding elements for the
transcriptional regulatory factor nuclear factor (NF)-
B are present
in the promoter regions of these cytokines and have important functions
in modulating their expression (5, 29). Increased nuclear
translocation of NF-
B occurs in the lungs after endotoxemia or
hemorrhage (31) and in lung cell populations of patients
with acute lung injury (28). NF-
B appears to play an
important role in the induction of acute lung injury because inhibition
of its activation is associated with decreased expression of
proinflammatory cytokines and amelioration of neutrophilic alveolitis
in experimental models (7, 31).
ROIs contribute to increased pulmonary production of proinflammatory
cytokines when ischemia-reperfusion injury is a major component of the pathophysiological process, as occurs with blood loss
(31). The role of ROIs in the pathogenesis of acute lung injury appears to be less important when the ischemic insult is less intense, such as after endotoxemia. For example, we found that
inhibition of the ROI-generating enzyme xanthine oxidase diminished
hemorrhage- but not endotoxemia-induced increases in the expression of
IL-1, MIP-2, and TNF-
among lung neutrophils (31).
In part, the role of ROIs in contributing to the development of acute
lung injury may be related to their role in activating NF-
B, thereby
increasing proinflammatory cytokine expression (30).
The activity of many inducible transcription factors, including
NF-B, is regulated through their association with cellular coactivators (10, 16, 17, 20, 32, 38). Interaction with
the coactivator cAMP response element binding protein (CREB)-binding protein (CBP) appears to be necessary to optimize the transcriptional activity of NF-
B (32, 38). In addition to interacting
with NF-
B, CBP also associates with TATA box-binding protein
(16) and transcription factor (TF) IIB (23),
becoming part of the general transcriptional apparatus. The interaction
of the p65 (Rel A) subunit of NF-
B with CBP involves the KIX region
of CBP, which is the same region responsible for binding the
transcriptionally active serine-133-phosphorylated form of CREB
(32, 38). Disruption of the KIX-based interactions between
CREB or NF-
B and CBP by mutagenesis significantly decreases the
efficiency of NF-
B- or CREB-dependent transcription
(38).
Because CBP is present in limiting amounts in the nucleus, competition
between NF-B and CREB for binding to CBP has been postulated to be
important in regulating the transcriptional activity of these factors
(38). In vitro studies have directly shown such
competition between p65 and CREB for limiting amounts of CBP
(38). Evidence for competitive interactions between
NF-
B and CREB has also been provided by Ollivier et al.
(22) and Parry and Mackman (24). In
their experiments, activation of protein kinase A resulted in increased
amounts of phosphorylated CREB and decreased NF-
B-mediated
transcription of TNF-
, endothelial leukocyte adhesion molecule-1,
and vascular cell adhesion molecule-1 but did not prevent nuclear
translocation of NF-
B heterodimers. However, there is little
information available on in vivo interactions between CBP, CREB, and
NF-
B.
In previous work with murine models of acute lung injury, our
laboratory (31) found that hemorrhage resulted in
increased expression of NF-B-dependent proinflammatory cytokines,
enhanced nuclear translocation of NF-
B, and increased levels of
serine-133-phosphorylated CREB in the lungs. Although xanthine oxidase
blockade prevented hemorrhage-induced increases in the expression of
NF-
B-dependent cytokines, such antioxidant therapy did not affect
nuclear translocation of NF-
B. However, inhibition of xanthine
oxidase before hemorrhage was found to result in further increases in
the amounts of phosphorylated CREB in the lungs. A possible explanation
for such findings is that the increased amounts of phosphorylated CREB
produced by xanthine oxidase inhibition before hemorrhage might compete
with NF-
B for limiting amounts of CBP, thereby reducing
NF-
B-dependent transcription. In the present studies, we directly
show that such interactions between NF-
B, CREB, and CBP occur in
vivo and are capable of modulating the transcriptional activity of
NF-
B and CREB.
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METHODS |
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Mice. Male BALB/c mice, 8-12 wk of age, were purchased from Harlan Sprague Dawley (Indianapolis, IN). The mice were kept on a 12:12-h light-dark cycle with free access to food and water. All experiments were conducted in accordance with institutional review board-approved protocols.
Materials. Isoflurane was obtained from Abbott Laboratories (North Chicago, IL). Escherichia coli 0111:B4 endotoxin and octylphenoxy poly(ethylenoxy)ethanol were obtained from Sigma (St. Louis, MO). The allopurinol-supplemented diet was purchased from ICN Biomedicals (Costa Mesa, CA). RPMI 1640 medium containing 25 mM HEPES and 300 mg/l of L-glutamine was obtained from BioWhittaker (Walkersville, MD). Protein A magnetic beads were obtained from Dynal (Lake Success, NY). The Coomassie Plus protein assay reagent, SuperSignal West Femto maximum sensitivity substrate, and anti-mouse secondary antibody conjugated to horseradish peroxidase were purchased from Pierce (Rockford, IL). The Hybond nitrocellulose and anti-rabbit secondary antibody conjugated to horseradish peroxidase were obtained from Amersham (Piscataway, NJ). Anti-CBP (A22), anti-CBP (C-1), and anti-CREB (24H4B) antisera were obtained from Santa Cruz Biotechnology (Santa Cruz, CA). Anti-p65 antiserum was obtained from BIOMOL (Plymouth Meeting, PA). The RNeasy kit was from QIAGEN (Valencia, CA). MIP-2, c-Fos, and rRNA control primers and probes, murine leukemia virus reverse transcriptase, and AmpliTaq Gold polymerase were purchased from PerkinElmer (Foster City, CA).
Models of hemorrhage and endotoxemia. The murine hemorrhage model used in these experiments was developed in our laboratory and has been reported previously (2, 31). With this model, 30% of the calculated blood volume (~0.55 ml for a 20-g mouse) is withdrawn by cardiac puncture from an isoflurane-anesthetized mouse over a 60-s period. The period of isoflurane anesthesia is <2 min in all cases. The mortality rate with this hemorrhage protocol is ~12%.
The model of endotoxemia was used as reported previously (31). Mice received an intraperitoneal injection of lipopolysaccharide at a dose of 1 mg/kg in 200 µl of PBS. This dose has previously been demonstrated to produce acute neutrophilic alveolitis, histologically consistent with acute lung injury in mice (11, 12).Allopurinol supplementation. To assess the effects of xanthine oxidase on cytokine expression and transcriptional factor activation, mice were pair-fed an allopurinol-supplemented diet (2.5 g/kg chow) or a normal control diet for 1 wk before hemorrhage or endotoxemia (4). Measured xanthine oxidase activity (33) in the lung was reduced from 7.4 ± 0.7 mU/g in control fed mice to essentially undetectable levels (0.2 ± 0.2 mU/g) in allopurinol-fed mice.
Excision of lungs. Briefly, the chest of the mouse was opened, and the lung vascular bed was flushed with 3-5 ml of chilled (4°C) PBS injected into the right ventricle. Lungs were then excised, avoiding the paratracheal lymph nodes, and washed twice in RPMI 1640 medium containing 25 mM HEPES-300 mg/l of L-glutamine with penicillin-streptomycin.
Coimmunoprecipitation. Interactions of CBP and p65 or CREB were demonstrated with a modification of the method of Gerritsen and coworkers (13). Lungs were homogenized in 1 ml of lysis buffer [25 mM HEPES · KOH, pH 7.2, 150 mM potassium acetate, 2 mM EDTA, 0.1% octylphenoxy poly(ethylenoxy)ethanol, 10 mM sodium fluoride, 1 mM phenylmethylsulfonyl fluoride, 10 µg/ml of leupeptin, 10 µg/ml of aprotinin, 1.5 µg/ml of pepstatin, and 5 mM dithiothreitol], incubated on ice for 10 min, and centrifuged at 12,000 g at 4°C. Lung extracts were isolated, and protein concentration was determined with Coomassie Plus protein assay reagent standardized to bovine serum albumin according to the manufacturer's protocol. Lung extracts (8 mg) were rotated for 1 h at 4°C with 20 µg of anti-CBP (A22) cross-linked to protein A magnetic beads according to the manufacturer's protocol. The beads were washed four times with 1 ml of lysis buffer and boiled for 5 min in SDS-denaturing sample buffer. Proteins were run through SDS-7.5% polyacrylamide gels and transferred to Hybond nitrocellulose for 16 h at 4°C. The membranes were blocked with 1% bovine serum albumin in a buffer containing 20 mM Tris · HCl, pH 7.6, 137 mM sodium chloride, and 0.5% Tween 20 (TBS-T) and incubated at a 1:1,000 dilution with anti-p65, anti-CREB, or anti-CBP (C-1) for 1 h at 20°C. Blots were washed three times with TBS-T buffer, incubated for 1 h with an anti-mouse or anti-rabbit secondary antibody conjugated to horseradish peroxidase, and washed 10 times in TBS-T. Proteins were visualized by incubation with SuperSignal West Femto maximum sensitivity substrate and with a ChemiDoc chemiluminescence detection system (Bio-Rad, Richmond, CA).
Quantitative PCR. RNA was isolated from whole lungs with an RNeasy kit according to the manufacturer's protocol. Briefly, lungs were homogenized for 30 s on ice in 300 µl of a buffer containing 25% guanidinium thiocyanate and 1% 2-mercaptoethanol. Samples were incubated with proteinase K at 55°C for 10 min, centrifuged at 12,000 g for 3 min, washed, incubated with DNase for 15 min at room temperature, and washed again. RNA was eluted from the membrane in 40 µl of RNase-free water, and the quantity of RNA was determined at an absorbance of 260 nm.
Primers and probes for MIP-2 and c-Fos were designed with the Primer Express software supplied by PerkinElmer. The MIP-2 primers and probes consisted of forward primer, 5'-TGTGACGCCCCCAGGA-3'; reverse primer, 5'-AACTTTTTGACCGCCCTTGAG-3'; and probe, 5'-TGCGCCCAGACAGAAGTCATAGCCA-3'. The c-Fos primers and probes consisted of forward primer, 5'-GGAATGGTGAAGACCGTGTCA-3'; reverse primer, 5'-CCTCTTCAGGAGATAGCTGCTCTAC-3'; and probe, 5'-CCTTCTGCCGATGCTCTGCGCT-3'. Based on primer optimization, conducted as described in the manufacturer's protocol, the primer concentration in the PCR was 10 nM forward primer and 450 nM reverse primer of the MIP-2 amplicon and 450 nM for both the forward and reverse primers of c-Fos. In each experiment, ribosomal control probe and forward and reverse primers at 50 nM were used to normalize the amount of RNA in each sample. One-step RT-PCRs of 50 µl consisted of reverse transcription for 30 min at 48°C with murine leukemia virus RT at 0.25 U/µl, followed by incubation for 10 min at 95°C and 40 cycles of amplification (95°C for 15 s and 60°C for 1 min) with AmpliTaq Gold polymerase at 0.025 U/µl. The quantity of MIP-2 and c-Fos mRNA was determined from a standard curve with 10-fold dilutions of known amounts of target RNA with each primer and probe set. RNA amounts were determined with software provided with the GeneAmp 5700 sequence detection system (ABI PRISM, Applied Biosystems, Foster City, CA). Quantification was determined by normalizing the amount of MIP-2 or c-Fos RNA by the amount of 18S rRNA.Statistical analysis. Because of inherent variability between groups of mice, for each experimental condition, the entire group of animals was prepared and studied at the same time. For each experimental condition, mice in all groups had the same birth date and had been housed together. Separate groups of mice were used for coimmunoprecipitations and quantitative PCR. For quantitative PCR, lung RNA was isolated from each individual animal and analyzed before group data were calculated. Data are presented as means ± SE for each experimental group. One-way analysis of variance, Tukey-Kramer test, Student-Newman-Keuls test, Dunnett's multiple comparisons, or Student's t-test were used for comparisons between data groups. P < 0.05 was considered significant.
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RESULTS |
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Interactions between p65 or CREB with
CBP after hemorrhage or endotoxemia.
Coimmunoprecipitation was used to determine the relative amounts of
CREB or p65 associated with CBP in the lungs after hemorrhage or
endotoxemia. As shown in Figs. 1 and
2, there were no changes in pulmonary
levels of CBP compared with those found in control unmanipulated mice during the 60 min after endotoxin administration or
blood loss.
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Xanthine oxidase inhibition modifies p65-CBP and
CREB-CBP interactions after hemorrhage.
In a previous study (31), we found that xanthine
oxidase-derived ROIs were responsible for hemorrhage- but not for
endotoxin-induced increases in the pulmonary expression of
proinflammatory cytokines. Despite the fact that transcription of such
cytokines is dependent on NF-B, xanthine oxidase inhibition did not
affect translocation of NF-
B to the nucleus after hemorrhage.
Because hemorrhage-induced CREB phosphorylation was further increased
after xanthine oxidase blockade, we hypothesized that increased amounts
of serine-133-phosphorylated CREB displaced NF-
B from the limiting
amounts of CBP present in the nucleus, thereby decreasing
NF-
B-dependent transcription.
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Modulation of p65-CBP and CREB-CBP
interactions in vivo affects CREB- and
NF-B-dependent gene transcription.
Because association with CBP is required for CREB- or NF-
B-dependent
transcription (10, 16, 17, 20, 32, 38), the effects of
xanthine oxidase inhibition in increasing CREB-CBP and decreasing
p65-CBP interactions should result in enhanced expression of
CREB-dependent genes and diminished expression of those dependent on
NF-
B. To determine if alterations in the association of CREB or p65
with CBP were functionally important and produced alterations in gene
expression in vivo, we examined levels of c-Fos and MIP-2 mRNA in the
lungs of hemorrhaged mice fed either a control or
allopurinol-containing xanthine oxidase-inhibiting diet. c-Fos
transcription is dependent on CREB (25), whereas that of
MIP-2 is NF-
B dependent (36).
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DISCUSSION |
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Transcriptional activation of both NF-B and CREB requires
association with the coactivator CBP (10, 16, 17, 20, 32, 38). Transcriptional coactivators such as CBP function by
facilitating or bridging sequence-specific activators such as NF-
B
or CREB to the basal transcriptional machinery, including the RNA
polymerase II holoenzyme, and altering chromatin structure. CBP
contains histone acetyltransferase (HAT) domains and has strong HAT
activity (6). CBP can recruit the CBP-associated factor
(p/CAF), which also has potent HAT activity, indicating that complexes
with multiple HAT activities can be formed (32). The
relative importance of the HAT activity of each coactivator appears to
vary depending on the transcriptional factor involved. For example,
CREB requires the HAT activity of CBP but not that of p/CAF
(19), whereas NF-
B utilizes the HAT activity of p/CAF
but not that of CBP (32).
Phosphorylation of NF-B or CREB stimulates transcriptional activity
by promoting interactions with CBP. For NF-
B, the required phosphorylation event involves serine-276 on the p65 subunit
(38). CBP has two sites that can interact with p65, an
NH2-terminal domain that associates with unphosphorylated
p65, and an S domain involving the KIX region, which can only interact
with serine-276-phosphorylated p65 (38). The p50 subunit
of the NF-
B heterodimer fails to recruit CBP (32).
Phosphorylation of serine-133 of CREB is required for association with
CBP, an event that also involves the KIX region of CBP (32,
38). Protein kinase A appears to be involved in phosphorylation
of both NF-
B and CREB (38). However, other kinases,
including p42/p44 extracellular signal-regulated kinases (ERKs), also
have been shown to phosphorylate serine-133 of CREB, leading to
transcriptional activation (9, 21, 26, 38).
Previous studies (13, 32, 38) showing association of CBP
with CREB or NF-B have all used in vitro or cell culture conditions, and little information was available concerning interactions between CBP and transcriptional factors under in vivo conditions relevant to
disease processes. In the present experiments, we examined p65-CBP and
CREB-CBP interactions in the lungs and found that hemorrhage or
endotoxemia resulted in increased association of NF-
B or CREB with
CBP. The enhanced interactions of NF-
B or CREB with CBP after
hemorrhage or endotoxemia appeared to have functional importance
because transcription of NF-
B- and CREB-dependent genes was
contemporaneously increased.
In the present experiments, interactions between NF-B, CREB, and CBP
were examined in whole lung homogenates. In our laboratory's previous
study (31), we demonstrated increased activation of NF-
B and CREB in neutrophils that accumulate in the lungs after hemorrhage or endotoxemia. Inhibition of xanthine oxidase resulted in
increased activation of CREB in lung neutrophils after hemorrhage but
not after endotoxemia (31). Similar to the results in the present studies in whole lungs, our laboratory (31)
previously demonstrated that xanthine oxidase blockade was associated
with decreased expression of NF-
B-dependent proinflammatory
cytokines in lung neutrophils after hemorrhage but not endotoxemia.
Abraham et al. (2) also showed that neutrophil depletion
significantly decreased endotoxin- or hemorrhage-induced NF-
B
activation in the lungs. Such results would suggest that alterations in
CREB-CBP and NF-
B-CBP among lung neutrophils are major contributors
to the observed responses between CREB, NF-
B, and CBP found in the lungs. However, NF-
B is activated in other pulmonary cells such as
alveolar macrophages (28) in acute lung injury, and these populations may play a role in determining interactions between CREB,
NF-
B, and CBP in whole lung preparations.
In the present experiments, we found that inhibition of xanthine
oxidase before hemorrhage could modulate association of CBP with CREB
or NF-B, providing a means to examine the importance of CREB-CBP and
NF-
B-CBP interactions on transcriptional activity in vivo. As
predicted by previous in vitro studies (22, 24, 38),
decreased association of NF-
B with CBP diminished NF-
B-dependent transcription, whereas increased interaction of CREB with CBP led to
enhanced expression of the CREB-dependent gene c-Fos.
Transfection experiments showing that increased expression of CBP
results in enhanced NF-B-dependent transcription indicate that the
amounts of CBP present in the nucleus are limiting (20). The present experiments, coupled with our laboratory's previous study
(31), support this hypothesis and suggest that limiting levels of CBP are important in regulating transcription in vivo. If the
amounts of CBP present in the lungs were not limiting, conditions that
increase amounts of phosphorylated CREB should result in enhanced
transcription of CREB-dependent genes without affecting
NF-
B-dependent transcription, a finding not observed in these experiments.
The immunomodulatory actions of xanthine oxidase activation observed in
the present studies were not unexpected. Previous work from our
laboratory (31) and others (3) has shown that xanthine oxidase is activated by hemorrhage and that such activation is
important in increasing transcription of NF-B-dependent
proinflammatory cytokines such as TNF-
and MIP-2. Xanthine
oxidase-derived ROIs also appear to modulate CREB phosphorylation
through their inhibitory effects on mitogen-activated protein kinase
kinase (MEK) 1/2 and ERK2 activity (1). ERK1/ERK2 can
phosphorylate serine-133 of CREB (9, 21, 26, 37). Our
laboratory (1) previously found that inhibition of
xanthine oxidase before blood loss, but not endotoxemia, enhanced MEK
1/2 and ERK2 activity, providing a mechanism by which hemorrhage could
affect CREB activation. In those experiments, interventions that
increased or decreased ERK2 activation after hemorrhage produced
parallel changes in the levels of phosphorylated CREB in the lungs.
An ancillary finding of the present experiments is that hemorrhage
appears to modulate interactions between CBP and CREB or NF-B by
mechanisms that are different from those initiated by endotoxemia.
Inhibition of xanthine oxidase before hemorrhage resulted in increased
association of CREB with CBP and decreased amounts of NF-
B bound to
CBP. In contrast, no such effects of xanthine oxidase blockade were
found after endotoxemia. These results indicate that the mechanisms
leading to acute inflammatory lung injury after blood loss or infection
are distinct, even though the clinical presentation in each setting is
similar. Such findings also suggest that early interventions aimed at
preventing acute lung injury may need to be different depending on the
clinical setting, with antioxidants having a greater role when
ischemic injury predominates, such as after severe blood loss.
The present results indicate that coactivators such as CBP have
important roles in modulating transcription in vivo under clinically
relevant pathophysiological conditions. As shown in these experiments,
reciprocal interactions between CREB and NF-B for binding to CBP
occur in vivo, providing an explanation for the ability of
manipulations that increase CREB phosphorylation to diminish
NF-
B-dependent transcription. Such findings indicate that even
though translocation of NF-
B to the nucleus and phosphorylation of
p65 are necessary to initiate transcription of NF-
B-dependent genes,
such events are not sufficient because additional regulatory events
independent of NF-
B activation may affect recruitment of CBP and
assembly of the transcriptional apparatus. In the present experiments,
interventions that increased levels of phosphorylated CREB resulted in
decreased association of NF-
B with CBP, suggesting that therapies
that increase CREB phosphorylation could be useful in diminishing
NF-
B-driven inflammatory responses in vivo. Other transcriptional
factors such as p53 can also compete with NF-
B, and presumably with
CREB, for interaction with CBP (35). Competitive interactions between transcriptional factors for association with a
coactivator such as CBP may have important therapeutic implications because interventions that modulate activation of one transcriptional factor are likely to affect expression of additional genes not directly
regulated by that factor.
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ACKNOWLEDGEMENTS |
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This work was supported by National Heart, Lung, and Blood Institute Grant HL-62221.
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FOOTNOTES |
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Address for reprint requests and other correspondence: E. Abraham, Div. of Pulmonary Sciences and Critical Care Medicine, Univ. of Colorado Health Sciences Ctr., Mail Code C-272, 4200 East Ninth Ave., Denver, CO 80262 (E-mail: edward.abraham{at}uchsc.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 22 January 2001; accepted in final form 22 March 2001.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Abraham, E,
Arcaroli J,
and
Shenkar R.
Activation of extracellular signal-regulated kinases, NF-B, and cyclic adenosine 5'-monophosphate response element-binding protein in lung neutrophils occurs by differing mechanisms after hemorrhage or endotoxemia.
J Immunol
166:
522-530,
2001
2.
Abraham, E,
Carmody A,
Shenkar R,
and
Arcaroli J.
Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury.
Am J Physiol Lung Cell Mol Physiol
279:
L1137-L1145,
2000
3.
Akgur, FM,
Brown MF,
Zibari GB,
McDonald JC,
Epstein CJ,
Ross CR,
and
Granger DN.
Role of superoxide in hemorrhagic shock-induced P-selectin expression.
Am J Physiol Heart Circ Physiol
279:
H791-H797,
2000
4.
Anderson, BO,
Moore EE,
Moore FA,
Leff JA,
Terada LS,
Harken AH,
and
Repine JE.
Hypovolemic shock promotes neutrophil sequestration in lungs by a xanthine oxidase-related mechanism.
J Appl Physiol
71:
1862-1865,
1991
5.
Baeuerle, PA,
and
Baltimore D.
NF-B: ten years after.
Cell
87:
13-20,
1996[ISI][Medline].
6.
Bannister, AJ,
and
Kouzarides T.
The CBP co-activator is a histone acetyltransferase.
Nature
384:
641-643,
1996[ISI][Medline].
7.
Blackwell, TS,
Blackwell TR,
Holden EP,
Christman BW,
and
Christman JW.
In vivo antioxidant treatment suppresses nuclear factor-B activation and neutrophilic lung inflammation.
J Immunol
157:
1630-1637,
1996[Abstract].
8.
Chollet-Martin, S,
Jourdain B,
Gibert C,
Elbim C,
Chastre J,
and
Gougerot-Pocidalo MA.
Interactions between neutrophils and cytokines in blood and alveolar spaces during ARDS.
Am J Respir Crit Care Med
154:
594-601,
1996[Abstract].
9.
Coffer, PJ,
Geijsen N,
M'rabet L,
Schweizer RC,
Maikoe T,
Raaijmakers JA,
Lammers JW,
and
Koenderman L.
Comparison of the roles of mitogen-activated protein kinase kinase and phosphatidylinositol 3-kinase signal transduction in neutrophil effector function.
Biochem J
329:
121-130,
1998[ISI][Medline].
10.
Dallas, PB,
Yaciuk P,
and
Moran E.
Characterization of monoclonal antibodies raised against p300: both p300 and CBP are present in intracellular TBP complexes.
J Virol
71:
1726-1731,
1997[Abstract].
11.
Faggioni, R,
Gatti S,
Demitri MT,
Delgado R,
Echtenacher B,
Gnocchi P,
Heremans H,
and
Ghezzi P.
Role of xanthine oxidase and reactive oxygen intermediates in LPS- and TNF-induced pulmonary edema.
J Lab Clin Med
123:
394-399,
1994[ISI][Medline].
12.
Gatti, S,
Faggioni R,
Echtenacher B,
and
Ghezzi P.
Role of tumour necrosis factor and reactive oxygen intermediates in lipopolysaccharide-induced pulmonary oedema and lethality.
Clin Exp Immunol
91:
456-461,
1993[ISI][Medline].
13.
Gerritsen, ME,
Williams AJ,
Neish AS,
Moore S,
Shi Y,
and
Collins T.
CREB-binding protein/p300 are transcriptional coactivators of p65.
Proc Natl Acad Sci USA
94:
2927-2932,
1997
14.
Goodman, RB,
Strieter RM,
Martin DP,
Steinberg KP,
Milberg JA,
Maunder RJ,
Kunkel SL,
Walz A,
Hudson LD,
and
Martin TR.
Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome.
Am J Respir Crit Care Med
154:
602-611,
1996[Abstract].
15.
Jacobs, RF,
Tabor DR,
Burks AW,
and
Campbell GD.
Elevated interleukin-1 release by human alveolar macrophages during the adult respiratory distress syndrome.
Am Rev Respir Dis
140:
1686-1692,
1989[ISI][Medline].
16.
Janknecht, R,
and
Hunter T.
Transcription. A growing coactivator network.
Nature
383:
22-23,
1996[ISI][Medline].
17.
Kingsley-Kallesen, ML,
Kelly D,
and
Rizzino A.
Transcriptional regulation of the transforming growth factor-beta2 promoter by cAMP-responsive element-binding protein (CREB) and activating transcription factor-1 (ATF-1) is modulated by protein kinases and the coactivators p300 and CREB-binding protein.
J Biol Chem
274:
34020-34028,
1999
18.
Kollef, MH,
and
Schuster DP.
The acute respiratory distress syndrome.
N Engl J Med
332:
27-37,
1995
19.
Korzus, E,
Torchia J,
Rose DW,
Xu L,
Kurokawa R,
McInerney EM,
Mullen TM,
Glass CK,
and
Rosenfeld MG.
Transcription factor-specific requirements for coactivators and their acetyltransferase functions.
Science
279:
703-707,
1998
20.
Kwok, RP,
Lundblad JR,
Chrivia JC,
Richards JP,
Bachinger HP,
Brennan RG,
Roberts SG,
Green MR,
and
Goodman RH.
Nuclear protein CBP is a coactivator for the transcription factor CREB.
Nature
370:
223-226,
1994[ISI][Medline].
21.
Obrietan, K,
Impey S,
Smith D,
Athos J,
and
Storm DR.
Circadian regulation of cAMP response element-mediated gene expression in the suprachiasmatic nuclei.
J Biol Chem
274:
17748-17756,
1999
22.
Ollivier, V,
Parry GCN,
Cobb RR,
de Prost D,
and
Mackman N.
Elevated cyclic AMP inhibits NF-B-mediated transcription in human monocytic cells and endothelial cells.
J Biol Chem
271:
20828-20835,
1996
23.
Parker, D,
Ferreri K,
Nakajima T,
LaMorte VJ,
Evans R,
Koerber SC,
Hoeger C,
and
Montminy MR.
Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism.
Mol Cell Biol
16:
694-703,
1996[Abstract].
24.
Parry, GC,
and
Mackman N.
Role of cyclic AMP response element-binding protein in cyclic AMP inhibition of NF-B-mediated transcription.
J Immunol
159:
5450-5456,
1997[Abstract].
25.
Pearman, AT,
Chou WY,
Bergman KD,
Pulumati MR,
and
Partridge NC.
Parathyroid hormone induces c-fos promoter activity in osteoblastic cells through phosphorylated cAMP response element (CRE)-binding protein binding to the major CRE.
J Biol Chem
271:
25715-25721,
1996
26.
Popik, W,
Hesselgesser JE,
and
Pitha PM.
Binding of human immunodeficiency virus type 1 to CD4 and CXCR4 receptors differentially regulates expression of inflammatory genes and activates the MEK/ERK signaling pathway.
J Virol
72:
6406-6413,
1998
27.
Repine, JE.
Scientific perspectives on adult respiratory distress syndrome.
Lancet
339:
466-469,
1992[ISI][Medline].
28.
Schwartz, MD,
Moore EE,
Moore FA,
Shenkar R,
Moine P,
Haenel JB,
and
Abraham E.
Nuclear factor-kappa B is activated in alveolar macrophages from patients with acute respiratory distress syndrome.
Crit Care Med
24:
1285-1292,
1996[ISI][Medline].
29.
Sha, WC.
Regulation of immune responses by NF-B/Rel transcription factor.
J Exp Med
187:
143-146,
1998
30.
Shenkar, R,
and
Abraham E.
Hemorrhage induces rapid in vivo activation of CREB and NF-B in murine intraparenchymal lung mononuclear cells.
Am J Respir Cell Mol Biol
16:
145-152,
1997[Abstract].
31.
Shenkar, R,
and
Abraham E.
Mechanisms of lung neutrophil activation after hemorrhage or endotoxemia: roles of reactive oxygen intermediates, NF-B, and cyclic AMP response element binding protein.
J Immunol
163:
954-962,
1999
32.
Sheppard, KA,
Rose DW,
Haque ZK,
Kurokawa R,
McInerney E,
Westin S,
Thanos D,
Rosenfeld MG,
Glass CK,
and
Collins T.
Transcriptional activation by NF-B requires multiple coactivators.
Mol Cell Biol
19:
6367-6378,
1999
32a.
Suter, PM,
Suter S,
Girardin E,
Roux-Lombard P,
Grau GE,
and
Dayer JM.
High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis.
Am Rev Respir Dis
145:
1016-1022,
1992[ISI][Medline].
33.
Terada, LS,
Dormish JJ,
Shanley PF,
Leff JA,
Anderson BO,
and
Repine JE.
Circulating xanthine oxidase mediates lung neutrophil sequestration after intestinal ischemia-reperfusion.
Am J Physiol Lung Cell Mol Physiol
263:
L394-L401,
1992
34.
Till, GO,
Friedl HP,
and
Ward PA.
Lung injury and complement activation: role of neutrophils and xanthine oxidase.
Free Radic Biol Med
10:
379-386,
1991[ISI][Medline].
35.
Wadgaonkar, R,
Phelps KM,
Haque Z,
Williams AJ,
Silverman ES,
and
Collins T.
CREB-binding protein is a nuclear integrator of nuclear factor-kappaB and p53 signaling.
J Biol Chem
274:
1879-1882,
1999
36.
Widmer, U,
Manogue KR,
Cerami A,
and
Sherry B.
Genomic cloning and promoter analysis of macrophage inflammatory protein (MIP)-2, MIP-1, and MIP-1
, members of the chemokine superfamily of proinflammatory cytokines.
J Immunol
150:
4996-5012,
1993
37.
Xing, J,
Ginty DD,
and
Greenberg ME.
Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase.
Science
273:
959-963,
1996[Abstract].
38.
Zhong, H,
Voll RE,
and
Ghosh S.
Phosphorylation of NF-B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300.
Mol Cell
1:
661-671,
1998[ISI][Medline].