Departments of 1 Surgery and 2 Medicine, University of Colorado Health Sciences Center, Denver, Colorado, 80262
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Expression of heat shock proteins (HSP) is an
adaptive response to cellular stress. Stress induces tumor necrosis
factor (TNF)- production. In turn, TNF-
induces HSP70 expression.
However, osmotic stress or ultraviolet radiation activates TNF-
receptor I (TNFR-I) in the absence of TNF-
. We postulated that
TNF-
receptors are involved in the induction of HSP70 by cellular
stress. Peritoneal M
were isolated from wild-type (WT), TNF-
knockout (KO), and TNFR (I or II) KO mice. Cells were cultured
overnight and then heat stressed at 43 ± 0.5°C for 30 min
followed by a 4-h recovery at 37°C. Cellular HSP70 expression was
induced by heat stress or exposure to endotoxin [lipopolysaccharide
(LPS)] as determined by immunoblotting. HSP70 expression induced by
either heat or LPS was markedly decreased in TNFR-I KO M
, whereas
TNFR-II KO M
exhibited HSP70 expression comparable to that in WT
mice. Expression of HSP70 after heat stress in TNF-
KO M
was also
similar to that in WT mice, suggesting that induction of HSP70 by
TNFR-I occurs independently of TNF-
. In addition, levels of
steady-state HSP70 mRNA were similar by RT-PCR in WT and TNFR-I KO M
despite differences in protein expression. Furthermore, the effect of TNFR-I appears to be cell specific, since HSP70 expression in splenocytes isolated from TNFR-I KO was similar to that in WT splenocytes. These studies demonstrate that TNFR-I is required for the
synthesis of HSP70 in stressed M
by a TNF-independent mechanism and
support an intracellular role for TNFR-I.
gene knockout; tumor necrosis factor-; reverse
transcription-polymerase chain reaction; splenocyte
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
EXPRESSION OF HEAT SHOCK PROTEINS (HSPs) is an endogenous mechanism promoting cellular adaptation to stress. The 70-kDa HSP family includes the inducible HSP72 and the constitutive HSP73. Though the functions of this family of stress proteins remain incompletely defined, the HSP70 family functions in both stress and nonstress conditions as a chaperone molecule that directs protein translocation within the cell, the folding of de novo proteins, and the degradation of denatured proteins (5, 15).
Induction of HSP70 confers increased survival following cellular insult
and occurs after exposure to a variety of stressors including heat
shock (12, 16), hypoxia (6), hemodynamic stress (13, 17), ultraviolet (UV) radiation
(27), and oxidant stress (26). Recent studies
also suggest that HSP70 is induced after exposure to proinflammatory
factors such as endotoxin [lipopolysaccharide (LPS)] or tumor
necrosis factor (TNF)- (21). In addition, HSP70 expression inhibits proinflammatory cytokine production by macrophages (25).
TNF- is a proinflammatory cytokine that binds two distinct members
of the TNF-
receptor superfamily. Activation of the p55 TNF-
Receptor I (TNFR-I) is responsible for many well-characterized effects
of TNF-
including translocation of nuclear factor (NF)-
B (7, 23), activation of the inflammatory cascade
(4), and initiation of apoptosis (28,
32). In addition to triggering a proinflammatory
cascade, however, TNF-
signals a compensatory cytoprotective
cellular response. This self-preservational profile is characterized by
the production of anti-inflammatory cytokines such as interleukin
(IL)-10 (31), production of IL-1 receptor antagonist
(30), release of soluble cytokine receptors such as
soluble TNFR-I and TNFR-II (29), and synthesis of cellular HSP70 (21). Targeted activation of this endogenous
cytoprotective cascade is an appealing clinical strategy to combat the
systemic inflammation that occurs in patients after severe injury.
Macrophages are often the source of the key mediators fueling the
posttraumatic systemic inflammatory response and, thus, should be an
ideal target for a therapeutic anti-inflammatory strategy. The role of
TNF- in macrophage HSP70 induction and the role for heat shock in
TNFR-I activation have not been described. Notably, however, UV light
and hyperosmotic stresses directly activate TNFR-I in HeLa cells
(19). Rosette and Karin (19) report TNFR-I
clustering and recruitment of the TNFR-I-associated death domain
(TRADD) after exposure to UV radiation or hyperosmotic stress.
Investigation of the role of the TNF-
receptor in heat stress-induced HSP70 expression is important for exploring the mechanism by which cells sense a stress as well as in understanding the
pathways responsible for the dynamic proinflammatory/cytoprotective balance within the cell.
Given the observation that the TNFR-I can be directly activated by
physical stress in the absence of its ligand (19), and given the simultaneous pro- and anti-inflammatory responses initiated by TNF-, we proposed a relationship between TNFR-I and the induction of HSP70. Therefore, the purposes of this study were to 1)
determine if TNFR-I and/or TNFR-II is required for induction of HSP70
in M
following heat stress or LPS, 2) evaluate whether
TNF-
is required for induction of HSP70 by heat stress,
3) ascertain whether the role of TNFR-I or TNFR-II in HSP70
induction is cell specific, and 4) determine whether TNF
receptors regulate HSP70 synthesis at the transcriptional or
posttranscriptional level.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Reagents.
Dulbecco's modified Eagle's culture medium (DMEM/F-12) supplemented
with 10 mM L-glutamine, 24 mM NaHCO3, 10 mM
HEPES, 10% fetal calf serum (FCS), and 150 ug/ml gentamicin were
purchased from GIBCO BRL (Gaithersburg, MD). FCS was purchased from
Life Technologies (Grand Island, NY). Lyophilized LPS (a
phenol-extracted preparation from Escherichia coli 055:B5)
as well as other reagents unless otherwise noted were purchased from
Sigma Chemical (St. Louis, MO). Murine TNF- was obtained from R&D
Systems (Minneapolis, MN). Four-domain soluble TNFR-I binding protein
(TNF bp) was a gift of Dr. Carl Edwards (Amgen, Thousand Oaks, CA). The
polyclonal rabbit antibody against the inducible form of HSP70 was
purchased from StressGen Biotechnologies (Victoria, BC, Canada.) This
antibody has no cross-reactivity to the constitutive isoforms of the
HSP70 family.
Mice.
Mice deficient in the TNF p55 receptor [TNFR-I knockout (KO)],
deficient in the TNF p75 receptor (TNFR-II KO), and matching the
C57BL/6J wild-type background were obtained from Jackson Laboratory (West Grove, PA). TNF- KO mice were generous gifts from Dr. D. W. Riches (National Jewish Medical Center, Denver, CO). Matching wild-type animals (B6-129) for TNF-
KO were obtained from
Jackson Laboratory. Animals were 7-9 wk old at the time of study
and were housed at the University of Colorado Health Sciences animal
care facility for at least 1 wk before being studied. Animals were allowed free access to food and water and were exposed to 12:12-h light-dark cycles before death. Animal experiments were
approved by the Animal Care and Research Committee, University of
Colorado Health Sciences Center. Animals received care in compliance
with the National Institutes of Health (NIH) Guide for the Care
and Use of Laboratory Animals [DHHS Publication No. (NIH) 85-23, Revised 1985, Office of Science and Health Reports, Bethesda, MD
20892]. Animals were killed with 50 mg/kg pentobarbital sodium by injection.
Cell culture and treatment.
Peritoneal M were isolated by peritoneal lavage. The peritoneal
cavity was lavaged twice (7 ml each) with filter-sterilized ice-cold
DMEM/F-12 and kept at 4°C. Cells pooled from animals of the same
genotype were centrifuged at 500 g for 10 min at 4°C and
then washed once with DMEM/F-12. Cells were counted with a hemacytometer and cultured at a density of 1-2 × 106 cells/ml in 20-mm tissue culture plates at 37°C in a
humidified 5% CO2 atmosphere. Nonadherent cells were
removed after 4 h at 37°C by washing once with warm medium. The
adherent cells were allowed to recover overnight. Cell viability was
confirmed at >95% using trypan blue exclusion. Cells were treated
with heat stress at 43.0 ± 0.5°C for 30 min. For HSP70 protein
assays, cells were allowed a 1-h recovery at 37°C before cells were
collected. For RNA isolation, cells from a parallel experiment were
collected after a 15-min recovery period at 37°C. Cells were
collected with a rubber scraper and gentle medium washes repeated three
times and were then stored as a dry pellet at
70°C.
Immunoblotting. Cell density was adjusted to a final concentration of 1 × 107 cells/ml in a lysis buffer containing 25 mM Tris · HCl, 2% SDS, 0.02% bromphenol blue, and 10% glycerol at pH 6.8. Samples were boiled for 5 min, vortexed, and placed on ice before loading. Protein concentration was measured by Coomassie Plus protein assay using BSA as the standard (Pierce, Rockford, IL). Electrophoresis was performed using 4-20% linear gradient SDS-polyacrylamide gels (Bio-Rad, Hercules, CA). After electrophoretic transfer to nitrocellulose membranes (Bio-Rad), membranes were stained with Ponceau S solution (Sigma) to assess equality of protein loading. After densitometry, membranes were washed and incubated in PBS containing 5% milk for 1 h. Membranes were then incubated in PBS with 0.1% Tween 20, 5% milk, and a 1:5,000 dilution of polyclonal antibody against HSP70 (StressGen). Horseradish peroxidase-conjugated goat anti-rabbit IgG at a 1:5,000 dilution was used as a detection antibody. The bands were visualized using an ECL (enhanced chemiluminescence) kit (Pierce) for 1 min, followed by exposure to film. Quantification of the immunoblots was performed by computer-assisted densitometry (NIH application 1.599b4). Relative density values are expressed as a percentage of the control value for each murine genotype evaluated. All densities are reported as means ± SE.
Murine cytokine assays.
TNF- in cell supernatants was determined using a murine TNF-
ELISA kit (R&D Systems) with a detection limit of 13.5 pg/ml. Samples
were run undiluted, in duplicate.
RNA isolation and RT-PCR. Total RNA was isolated from peritoneal macrophages or splenocytes using Tri-Reagent (Molecular Research Center, Cincinnati, OH). Cells were lysed in Tri-reagent, and RNA was sequentially isolated using chloroform extraction and isopropanol precipitation. RNA was dissolved in diethyl pyrocarbonate-treated water and quantified using GeneQuant (Pharmacia Biotech, Cambridge, UK). To prepare cDNA, 0.5-2 ug of total RNA were reverse-transcribed using random primers in a final concentration of 5 mM MgCl2, 50 mM KCl, and 10 mM Tris · HCl (pH 8.3), 1 mM of each dNTP, 20 units of RNase inhibitor, and 50 units of MuLV reverse transcriptase (Perkin Elmer, Branchburg, NJ.) The reaction was incubated at 42°C for 40 min and terminated at 95°C for 5 min. PCR was performed using HotStarTaq DNA polymerase and the Q-Solution Kit (Qiagen, Valencia, CA) in accordance with the manufacturer's protocol. Briefly, 2 µl of RT product were used in a total volume of 50 µl containing 5 µl of 10× PCR buffer, 10 µl of 5× Q-solution, 0.2 mM of each dNTP, and 1.5 units of HotStarTaq Polymerase (Qiagen). The sense primer for HSP70 was 5'-AAACTCCCTCCCTGGTCTGA, and the reverse primer was 5'-CTTGTCTTCGCTTGTCTCTG. The sense primer for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was 5'-ACCACAGTCCATGCCATCAC, and the reverse primer was 5'-AGGTGGTGGGACAACGACAT (GIBCO BRL, Rockville, MD). PCR was performed on a Peltier Thermal Cycler-200 (MJ Research, Watertown, MA). For each PCR reaction, the following sequence was used: preheating at 95°C for 15 min, then at 94°C for 40 s, 55°C for 45 s, and 75°C for 1 min, with a final extension phase at 72°C for 10 min. A variable number of cycles from 25 to 40 were used to ensure that amplification occurred in the linear phase and that differences between control and experimental conditions were maintained by adopting a limited number of cycles. The optimal number of cycles was established at 35. The PCR amplification using GAPDH as the internal control was performed on each sample to ensure that differences between tubes were not the result of unequal concentrations of RNA. The PCR products were separated on a 1.5% agarose gel containing 0.5× TBE (50 mM Tris, 45 mM boric acid, 0.5 mM EDTA, pH 8.3) with 0.5 ug/ml ethidium bromide, visualized by UV illumination, and photographed. Densitometry was performed on the negative image (ImageQuant software; Molecular Dynamics, Sunnyvale, CA), and the relative absorbance of the HSP70 PCR products was corrected against the absorbance obtained for GAPDH.
Statistical analysis. Data were expressed as means ± SE. An analysis of variance was performed, and a difference was accepted as significant with P < 0.05 verified by a Bonferroni/Dunn post hoc test.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Role of TNF receptors in heat stress induction of
M HSP70.
Baseline HSP70 levels were undetectable or barely detectable in
peritoneal M
isolated from wild-type mice and mutant mice lacking
TNFR-I or TNFR-II. Heat stress induced HSP70 in peritoneal M
isolated from wild-type mice. However, the presence of HSP70 was
markedly reduced in the TNFR-I KO cells (Fig.
1). In contrast, stress-induced HSP70
synthesis was preserved in M
isolated from TNFR-II KO mice.
|
Role of TNF- in heat stress induction of
M
HSP70.
To determine whether the attenuation of heat stress-induced HSP70
production in TNFR-I KO M
was mediated through TNF-
, we examined
whether heat stress upregulates TNF-
release. As a positive control,
TNF-
was induced by LPS stimulation in M
isolated from wild-type
mice and mutant mice lacking TNFR-I or TNFR-II. Cells were exposed to
media containing 500 ng/ml E. coli LPS for 4 h, and the
supernatants were collected. For heat stress treatment, cells were
placed at 43°C for 30 min as described in MATERIALS AND
METHODS. Supernatants were collected after a 4-h recovery at
37°C. TNF-
release was not detected in supernatants following heat
stress regardless of the phenotype of the cells (Fig.
2). Given the described autocrine
function of TNF-
(24), we determined the role of this
cytokine in heat stress-induced M
HSP70 production using M
lacking TNF-
. Indeed, HSP70 production was preserved in M
isolated from TNF-
KO mice (Fig. 3).
|
|
Role of TNF receptors and TNF-
binding protein in induction of M
HSP70 by LPS.
As in heat stressed M
, baseline HSP70 levels were undetectable or
barely detectable in peritoneal M
isolated from wild-type mice and
mutant mice lacking TNFR-I or TNFR-II. However, LPS treatment induced
HSP70 in peritoneal M
isolated from wild-type mice. As above, HSP70
production was markedly reduced in the TNFR-I KO cells (Fig.
4). However, since LPS treatment induced
TNF-
production whereas heat stress did not (Fig. 2), the ligand
responsible for activation of TNFR-I following these two stressors may
be different. To block activation of TNFR-I by LPS-induced TNF
production, wild-type M
were stimulated with LPS in the presence of
saturating concentrations of TNF bp. Treatment of wild-type M
with
TNF bp before exposure to LPS prevented HSP70 induction (Fig.
5), whereas HSP70 induction by heat
stress was preserved (Fig. 6). These data
suggest that LPS induction of HSP70 is dependent on activation of TNF
receptors by TNF, whereas heat stress induction of HSP70 regulated by
TNFR-I is TNF-
independent.
|
|
|
Influence of TNFR-I on HSP70 gene
expression.
We next determined whether the lack of HSP70 production in peritoneal
M of TNFR-I KO mice correlated to HSP70 gene transcription. HSP70
mRNA levels were examined using semi-quantitative RT-PCR. HSP70 mRNA
was not present in either wild-type or TNFR-I KO cells before heat
stress. Heat stress strongly induced HSP70 mRNA production in wild-type
cells. Despite the reduced HSP70 protein synthesis in M
lacking
TNFR-I, HSP70 mRNA levels following heat stress in this phenotype were
similar to those in wild-type M
(Fig. 7).
|
Cell-type specificity of regulating HSP70 production
by TNFR-I.
To investigate whether the influence of TNFR-I on HSP70 production was
specific to M, we examined HSP70 production in splenocytes following
an exposure to identical heat stress. In contrast to peritoneal M
,
splenocytes lacking TNFR-I retained the capability of expressing HSP70
mRNA and protein (Figs. 8 and
9).
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In the present study, we determined that synthesis of HSP70 is
nearly absent in peritoneal M from mice lacking TNFR-I by a
TNF-
-independent mechanism. However, TNF-
has been demonstrated to induce HSP70 in fibroblasts (21). The ability of
TNF-
to induce HSP70 is thought to be part of the stress response,
since direct activation of the TNFR-I by physical stress (UV radiation or osmotic stress) was reported in a previous study (19).
In addition, in HeLa cells transfected with antisense TNF-
mRNA to
inhibit endogenous TNF-
, decreased HSP70 production, increased sensitivity to heat, and increased binding of heat shock factor 1 (HSF1) to heat shock element were observed (33, 34). These results suggest that TNFR-I regulates HSP70 expression induced by both
TNF-
-dependent (LPS) and -independent (heat stress) mechanisms. The
regulation is specific to macrophages and appears to be at the level of translation.
In the present study, we have demonstrated a link between TNFR-I and
HSP70 expression in the macrophage, a principal cell mediating the
inflammatory response. The results of the present study indicate that
1) TNFR-I is required for synthesis of M HSP70 by heat
stress; 2) the influence of TNFR-I on heat stress induction
of M
HSP70 is independent of TNF-
, whereas LPS induction of HSP70
depends on TNF-
; 3) the requirement for TNFR-I in HSP70 induction is cell specific, being essential in M
but not in
splenocytes; and 4) TNFR-I regulates M
HSP70 production
at the posttranscriptional level.
A relationship between a non-TNF--activated pathway for TNFR-I and
induction of HSP70 has not been previously described. Our data suggest
an intracellular role for TNFR-I in the production of HSP70. TNFR-I
signaling involves a duality in which pathways leading to
apoptosis are activated along with mechanisms of cellular protection. TNFR-I activation leads to trimerization and recruitment of
TRADD, a secondary intracellular mediator that subsequently ligates
TNF-
receptor-associated factor 2 (TRAF2) and Fas-associated death
domain (FADD). TRAF2 activates NF
-B, which has
antiapoptotic effects, while FADD binds both to the
proapoptotic cell-surface receptor Fas and is required for TNFR I
signaling of apoptosis (8). Activation of Fas
inhibits HSF1 and the subsequent induction of HSP70 (22).
Because HSP70 has been shown to be antiapoptotic (3,
11), suppression of HSP70 by expression by Fas signaling may
ensure the execution of programmed cell death. In the present study,
HSP70 production was nearly absent following heat stress or LPS
exposure in TNFR-I KO M
, suggesting that TNFR-I is required for M
HSP70 induction by either stress. Alternatively, the intracellular presence of TNFR-I, rather than its extracellular activation, may be
responsible for M
HSP70 synthesis. Because TNFR-I activation was not
measured in this study, it remains unclear whether TNFR-I influences
HSP70 synthesis via activation or by a mechanism independent of
receptor activation. However, blocking TNF receptors with TNF bp had an
effect on LPS-induced HSP70 induction similar to that in the absence of
TNFR-I, suggesting that ligand binding and activation of the receptor
plays a role in synthesis of HSP70.
It is always possible that the lack of heat stress induction of HSP70
in the TNFR I KO M is due to a genetic alteration related to a
life-long absence of the TNFR-I. However, the ability of TNFR I KO
splenocytes to produce HSP70 in response to heat stress argues against
an inability to produce HSP70 secondary to altered genetic component
from conception. Therefore, despite the limitations of the KO model,
the evidence appears compelling in support of a role of the TNFR I in
regulating heat stress induction of macrophage HSP70. Posttranslational
stability of HSP70 protein may be a factor determining cellular HSP70
level following stress, and intracellular TNFR-I may stabilize HSP70.
However, it is unlikely that HSP70 is rapidly degraded in cells lacking
TNFR-I, since a similar difference in stability of HSP70 would be
anticipated in TNFR-I KO splenocytes. Moreover, no additional bands of
smaller molecular size were observed by immunoblotting in TNFR-I KO
M
following exposure to stress.
Because TNF- induces HSP70 in several cell types and has been
implicated as a mediator of heat stress-induced HSP70 expression (21), we anticipated that the decreased expression of
HSP70 in the TNFR-I KO M
would be related to heat-induced TNF-
.
Thus we examined M
TNF-
production following heat stress.
Surprisingly, we found that TNF-
was not synthesized following heat
stress in any genotype examined (wild type, TNFR I KO, and TNFR II KO), although all genotypes synthesized TNF-
in response to LPS
stimulation. Thus the effect of TNFR-I on heat stress-induced M
HSP70 is independent of TNF-
. This notion is further supported by
our observation that heat stress induction of HSP70 in TNF-
KO M
is similar to that in wild-type M
and by the lack of suppression of
heat-induced HSP70 production by TNF bp in wild-type M
.
The results of the present study suggest that the TNFR-I regulates
HSP70 production by both TNF--dependent and -independent pathways.
In addition, TNFR-I regulation of M
HSP70 production occurs at the
posttranscriptional level. Furthermore, this effect is cell-type
dependent. Macrophages isolated from TNFR-I KO mice show attenuated
HSP70 induction following stress, while TNFR-I KO splenocytes show
stress-induced HSP70 that is similar to wild type. This differential
effect may be related to cellular trafficking pathways unique to the
macrophage, such as its role as an antigen-presenting cell. Macrophages
are central to the inflammatory response, releasing the proximal
mediators of the proinflammatory cascade, such as TNF-
. Splenocytes
are composed of a heterogeneous cell population, with a majority being
T cells that can be activated by macrophages. The primary role of the
macrophage in the immune response may explain the differential response
seen between splenocytes and macrophages. Alternatively, the
heterogenous nature of the splenocyte population may be important.
A number of studies demonstrate that the regulation of HSP70 induction
is mediated at the level of transcription via DNA binding of HSF1
(1, 20). In our study, however, comparable steady-state levels of HSP70 mRNA were detected by RT-PCR in wild-type and TNFR-I KO
M despite differences in protein expression. Our results suggest an
additional level of complexity in the regulation of HSP70 induction,
which appears to be at the posttranscriptional level.
Posttranscriptional regulation of protein expression may occur at the
ribosomal binding of eukaryotic initiation factors (9). An
additional mechanism of regulation of protein expression is the rate of
mRNA degradation (10). It is possible that differential mRNA expression may be seen over time, though stable HSP70 mRNA has
been observed by multiple investigators (14, 26). Because HSP70 mRNA transcript production is similar in TNFR-I KO and wild-type M
, posttranscriptional regulation by TNFR-I may involve
translational machinery. Heat stress leads to the inhibition
of normal cellular protein mRNA translation, with the preferential
translation of HSP mRNA. This differential regulation of protein
expression may occur at the ribosomal binding of eukaryotic initiation
factors (9). Eukaryotic initiation factor 4F (eIF-4F) has
been demonstrated to rescue protein synthesis in cell-free systems
prepared from heat-shocked cells, while translation of heat shock mRNA
is not affected by the loss of eIF-4F and, thus, is a possible
contributing mechanism for the preferential translation of HSP mRNA.
The regulation of eIF-4F is incompletely understood, but perhaps TNFR-I
activation plays a role. The mechanism by which TNFR-I regulates M
HSP70 expression remains to be defined, though investigation of normal cellular mRNA translation in TNFR-I KO macrophages following heat shock
may be helpful in elucidating the potential role of initiation factors.
![]() |
ACKNOWLEDGEMENTS |
---|
We are grateful to Lihua Ao for technical assistance in immunoblotting.
![]() |
FOOTNOTES |
---|
This work was supported in part by National Institutes of Health Grants GM-49222, GM-08315, AI-15614, and AI-2532359.
Address for reprint requests and other correspondence: J. K. Heimbach, Dept. of Surgery, 4200 E. 9th Ave., Denver, CO 80262 (E-mail: julie.heimbach{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 19 September 2000; accepted in final form 1 February 2001.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Baler, R,
Dahl G,
and
Voellmy R.
Activation of human heat shock genes is accompanied by oligomerization, modification, and rapid translocation of heat shock transcription factor HSF1.
Mol Cell Biol
13:
2486-2496,
1993[Abstract].
2.
Coligan, J,
Kruisbeek K,
Margulies D,
Shevach E,
and
Strober W.
In vitro assays for mouse lymphocyte function.
In: Current Protocols in Immunology. New York: Wiley, 1992, vol. 1.
3.
Creagh, EM,
Carmody RJ,
and
Cotter TG.
Heat shock protein 70 inhibits caspase-dependent and -independent apoptosis in Jurkat T cells.
Exp Cell Res
257:
58-66,
2000[ISI][Medline].
4.
Fiers, W.
Tumor necrosis factor. Characterization at the molecular, cellular and in vivo level.
FEBS Lett
285:
199-212,
1991[ISI][Medline].
5.
Hartl, FU.
Molecular chaperones in cellular protein folding.
Nature
381:
571-579,
1996[ISI][Medline].
6.
Heads, RJ,
Yellon DM,
and
Latchman DS.
Differential cytoprotection against heat stress or hypoxia following expression of specific stress protein genes in myogenic cells.
J Mol Cell Cardiol
27:
1669-1678,
1995[ISI][Medline].
7.
Hsu, H,
Xiong J,
and
Goeddel DV.
The TNF receptor 1-associated protein TRADD signals cell death and NF-B activation.
Cell
81:
495-504,
1995[ISI][Medline].
8.
Jiang, Y,
Woronicz JD,
Liu W,
and
Goeddel DV.
Prevention of constitutive TNF receptor 1 signaling by silencer of death domains.
Science
283:
543-546,
1999
9.
Joshi-Barve, S,
De Benedetti A,
and
Rhoads RE.
Preferential translation of heat shock mRNAs in HeLa cells deficient in protein synthesis initiation factors eIF-4E and eIF-4 gamma.
J Biol Chem
267:
21038-21043,
1992
10.
Laroia, G,
Cuesta R,
Brewer G,
and
Schneider RJ.
Control of mRNA decay by heat shock-ubiquitin-proteasome pathway.
Science
284:
499-502,
1999
11.
Li, CY,
Lee JS,
Ko YG,
Kim JI,
and
Seo JS.
Heat shock protein 70 inhibits apoptosis downstream of cytochrome c release and upstream of caspase-3 activation.
J Biol Chem
275:
25665-25671,
2000
12.
Marber, MS,
and
Yellon DM.
Myocardial adaptation, stress proteins, and the second window of protection.
Ann NY Acad Sci
793:
123-141,
1996[Medline].
13.
Meng, X,
Brown JM,
Ao L,
Nordeen SK,
Franklin W,
Harken AH,
and
Banerjee A.
Endotoxin induces cardiac HSP70 and resistance to endotoxemic myocardial depression in rats.
Am J Physiol Cell Physiol
271:
C1316-C1324,
1996
14.
Moore, M,
Schaack J,
Baim SB,
Morimoto RI,
and
Shenk T.
Induced heat shock mRNAs escape the nucleocytoplasmic transport block in adenovirus-infected HeLa cells.
Mol Cell Biol
7:
4505-4512,
1987[ISI][Medline].
15.
Morimoto, RI,
Sarge KD,
and
Abravaya K.
Transcriptional regulation of heat shock genes. A paradigm for inducible genomic responses.
J Biol Chem
267:
21987-21990,
1992
16.
Nwaka, S,
Mechler B,
von Ahsen O,
and
Holzer H.
The heat shock factor and mitochondrial Hsp70 are necessary for survival of heat shock in Saccharomyces cerevisiae.
FEBS Lett
399:
259-263,
1996[ISI][Medline].
17.
Plumier, JC,
Robertson HA,
and
Currie RW.
Differential accumulation of mRNA for immediate early genes and heat shock genes in heart after ischaemic injury.
J Mol Cell Cardiol
28:
1251-1260,
1996[ISI][Medline].
18.
Reznikov, LL,
Shames BD,
Barton HA,
Selzman CH,
Fantuzzi G,
Kim SH,
Johnson SM,
and
Dinarello CA.
Interleukin-1 deficiency results in reduced NF-
B levels in pregnant mice.
Am J Physiol Regulatory Integrative Comp Physiol
278:
R263-R270,
2000
19.
Rosette, C,
and
Karin M.
Ultraviolet light and osmotic stress: activation of the JNK cascade through multiple growth factor and cytokine receptors.
Science
274:
1194-1197,
1996
20.
Sarge, KD,
Murphy SP,
and
Morimoto RI.
Activation of heat shock gene transcription by heat shock factor 1 involves oligomerization, acquisition of DNA-binding activity, and nuclear localization and can occur in the absence of stress.
Mol Cell Biol
13:
1392-1407,
1993[Abstract].
21.
Schett, G,
Redlich K,
Xu Q,
Bizan P,
Groger M,
Tohidast-Akrad M,
Kiener H,
Smolen J,
and
Steiner G.
Enhanced expression of heat shock protein 70 (hsp70) and heat shock factor 1 (HSF1) activation in rheumatoid arthritis synovial tissue. Differential regulation of hsp70 expression and hsf1 activation in synovial fibroblasts by proinflammatory cytokines, shear stress, and antiinflammatory drugs.
J Clin Invest
102:
302-311,
1998
22.
Schett, G,
Steiner CW,
Groger M,
Winkler S,
Graninger W,
Smolen J,
Xu Q,
and
Steiner G.
Activation of Fas inhibits heat-induced activation of HSF1 and up-regulation of hsp70.
FASEB J
13:
833-842,
1999
23.
Shames, BD,
Meldrum DR,
Selzman CH,
Pulido EJ,
Cain BS,
Banerjee A,
Harken AH,
and
Meng X.
Increased levels of myocardial IB-
protein promote tolerance to endotoxin.
Am J Physiol Heart Circ Physiol
275:
H1084-H1091,
1998
24.
Sherry, B,
and
Cerami A.
Cachectin/tumor necrosis factor exerts endocrine, paracrine, and autocrine control of inflammatory responses.
J Cell Biol
107:
1269-1277,
1988[ISI][Medline].
25.
Snyder, YM,
Guthrie L,
Evans GF,
and
Zuckerman SH.
Transcriptional inhibition of endotoxin-induced monokine synthesis following heat shock in murine peritoneal macrophages.
J Leukoc Biol
51:
181-187,
1992[Abstract].
26.
Steiner, E,
Kleinhappl B,
Gutschi A,
and
Marth E.
Analysis of hsp70 mRNA levels in HepG2 cells exposed to various metals differing in toxicity.
Toxicol Lett
96-97:
169-176,
1998.
27.
Suzuki, K,
and
Watanabe M.
Modulation of cell growth and mutation induction by introduction of the expression vector of human hsp70 gene.
Exp Cell Res
215:
75-81,
1994[ISI][Medline].
28.
Tartaglia, LA,
Ayres TM,
Wong GH,
and
Goeddel DV.
A novel domain within the 55 kD TNF receptor signals cell death.
Cell
74:
845-853,
1993[ISI][Medline].
29.
Van der Poll, T,
Calvano SE,
Kumar A,
Braxton CC,
Coyle SM,
Barbosa K,
Moldawer LL,
and
Lowry SF.
Endotoxin induces downregulation of tumor necrosis factor receptors on circulating monocytes and granulocytes in humans.
Blood
86:
2754-2759,
1995
30.
Van der Poll T and van Deventer SJ. Cytokines and anticytokines in
the pathogenesis of sepsis. Infect Dis Clin North Am 13:
413-426, ix, 1999.
31.
Wanidworanun, C,
and
Strober W.
Predominant role of tumor necrosis factor-alpha in human monocyte IL-10 synthesis.
J Immunol
151:
6853-6861,
1993
32.
Ware, CF,
VanArsdale S,
and
VanArsdale TL.
Apoptosis mediated by the TNF-related cytokine and receptor families.
J Cell Biochem
60:
47-55,
1996[ISI][Medline].
33.
Watanabe, N,
Tsuji N,
Akiyama S,
Sasaki H,
Okamoto T,
Kobayashi D,
Sato T,
Hagino T,
Yamauchi N,
and
Niitsu Y.
Endogenous tumour necrosis factor regulates heat-inducible heat shock protein 72 synthesis.
Int J Hyperthermia
14:
309-317,
1998[ISI][Medline].
34.
Watanabe, N,
Tsuji N,
Akiyama S,
Sasaki H,
Okamoto T,
Kobayashi D,
Sato T,
Hagino T,
Yamauchi N,
Niitsu Y,
Nakai A,
and
Nagata K.
Induction of heat shock protein 72 synthesis by endogenous tumor necrosis factor via enhancement of the heat shock element-binding activity of heat shock factor 1.
Eur J Immunol
27:
2830-2834,
1997[ISI][Medline].