Central nervous
system
BMC Neurosci. 2006 Jan 23;7:6. Expression
of hepatoma-derived growth factor family members
in the adult central nervous system. ·
El-Tahir HM, Dietz F, Dringen
R, Schwabe
K, Strenge
K, Kelm
S, Abouzied
MM, Gieselmann
V, Franken S.
Institut fur Physiologische
Chemie, Rheinische
Friedrich-Wilhelms Universitat,
Nussallee 11, 53115 BACKGROUND: Hepatoma-derived
growth factor (HDGF) belongs to a polypeptide family containing five
additional members called HDGF related proteins 1-4 (HRP-1 to -4) and Lens
epithelial derived growth factor. Whereas some family members such as HDGF
and HRP-2 are expressed in a wide range of tissues, the expression of
others is very restricted. HRP-1 and -4 are only expressed in testis, HRP-3
only in the nervous system. Here we investigated the expression of HDGF,
HRP-2 and HRP-3 in the central nervous system of adult rats on the cellular
level by immunohistochemistry. In addition we
performed Western blot analysis of various brain regions as well as
neuronal and glial cell cultures. RESULTS: HDGF
was rather evenly expressed throughout all brain regions tested with the
lowest expression in the substantia nigra. HRP-2 was strongly expressed in the thalamus,
prefrontal and parietal cortex, neurohypophysis,
and the cerebellum, HRP-3 in the bulbus olfactorius, piriform cortex
and amygdala complex. HDGF and HRP-2 were found
to be expressed by neurons, astrocytes and oligodendrocytes. In contrast, strong expression of
HRP-3 in the adult nervous system is restricted to neurons, except for very
weak expression in oligodendrocytes in the brain
stem. Although the majority of neurons are HRP-3 positive, some like cerebellar granule cells are negative. CONCLUSION: The coexpression of HDGF and HRP-2 in glia
and neurons as well as the coexpression of all
three proteins in many neurons suggests different functions of members of
the HDGF protein family in cells of the central nervous system that might
include proliferation as well as cell survival. In addition the restricted
expression of HRP-3 point to a special function of this family member for
neuronal cells. PMID: 16430771 [PubMed -
indexed for MEDLINE J Neurochem.
2006 Oct;99(1):70-83. Hepatoma-derived growth factor, a new trophic factor for motor neurons, is up-regulated in
the spinal cord of PQBP-1 transgenic mice before onset of degeneration. ·
Marubuchi S, Okuda T, Tagawa K, Enokido Y, Horiuchi D, Shimokawa R, Tamura T, Qi ML, Eishi Y, Watabe K, Shibata M, Nakagawa M, Okazawa H. Department of Neuropathology, Medical Research
Institute and 21st Century Center of Excellence Program for Brain
Integration and Its Disorders, Tokyo Medical and Dental University, Tokyo,
Japan. Hepatoma-derived growth factor (HDGF)
is a nuclear protein homologous to the high-mobility group B1 family of
proteins. It is known to be released from cells and to act as a trophic factor for dividing cells. In this study HDGF
was increased in spinal motor neurons of a mouse model of motor neuron
degeneration, polyglutamine-tract-binding
protein-1 (PQBP-1) transgenic mice, before onset of degeneration. HDGF
promoted neurite extension and survival of spinal
motor neurons in primary culture. HDGF repressed cell death of motor neurons
after facial nerve section in newborn rats in vivo. We also found a
significant increase in p53 in spinal motor neurons of the transgenic mice.
p53 bound to a sequence in the upstream of the
HDGF gene in a gel mobility shift assay, and promoted gene expression
through the cis-element in chloramphenicol
acetyl transfer (CAT) assay. Finally, we found that HDGF was increased in
CSF of PQBP-1 transgenic mice. Collectively, our results show that HDGF is
a novel trophic factor for motor neurons and
suggest that it might play a protective role against motor neuron
degeneration in PQBP-1 transgenic mice. PMID: 16987236 [PubMed -
indexed for MEDLINE J Neurochem.
2006 Oct;99(1):70-83. Hepatoma-derived growth factor, a new trophic factor for motor neurons, is up-regulated in
the spinal cord of PQBP-1 transgenic mice before onset of degeneration. ·
Marubuchi S, Okuda T, Tagawa K, Enokido Y, Horiuchi D, Shimokawa R, Tamura T, Qi ML, Eishi Y, Watabe K, Shibata M, Nakagawa M, Okazawa H. Department of Neuropathology, Medical Research
Institute and 21st Century Center of Excellence Program for Brain
Integration and Its Disorders, Tokyo Medical and Dental University, Tokyo,
Japan. Hepatoma-derived growth factor (HDGF)
is a nuclear protein homologous to the high-mobility group B1 family of
proteins. It is known to be released from cells and to act as a trophic factor for dividing cells. In this study HDGF
was increased in spinal motor neurons of a mouse model of motor neuron
degeneration, polyglutamine-tract-binding
protein-1 (PQBP-1) transgenic mice, before onset of degeneration. HDGF
promoted neurite extension and survival of spinal
motor neurons in primary culture. HDGF repressed cell death of motor
neurons after facial nerve section in newborn rats in vivo. We also found a
significant increase in p53 in spinal motor neurons of the transgenic mice.
p53 bound to a sequence in the upstream of the
HDGF gene in a gel mobility shift assay, and promoted gene expression
through the cis-element in chloramphenicol
acetyl transfer (CAT) assay. Finally, we found that HDGF was increased in
CSF of PQBP-1 transgenic mice. Collectively, our results show that HDGF is
a novel trophic factor for motor neurons and
suggest that it might play a protective role against motor neuron
degeneration in PQBP-1 transgenic mice. PMID: 16987236 [PubMed -
indexed for MEDLINE] J
Allergy Clin Immunol.
2005 Dec;116(6):1256-63. Am
J Respir Crit Care
Med. 2005 Feb 15;171(4):305-14. Epub 2004 Nov 5. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Sep;27(9):585-8. Differential Regulation of CD40-Mediated TNF
Receptor-Associated Factor Degradation in B Lymphocytes. B Cell Maturation Antigen, the Receptor
for a Proliferation-Inducing Ligand and B
Cell-Activating Factor of the TNF Family, Induces Antigen Presentation in B
Cells. ICAM-1 gene expression in endothelial cells: Effects on the
inhibition of STAT3 phosphorylation.
Links
Links
Chronic exposure to TNF-alpha increases
airway mucus gene expression in vivo.
Busse PJ, Zhang TF, Srivastava K,
Lin BP, Schofield B,
Sealfon SC,
Li XM.
Division of Clinical Immunology,
BACKGROUND: Hypersecretion of mucus plays an
important role in the pathogenesis and severity of asthma. The primary
proteins in mucus are mucin glycoproteins;
MUC-5AC is the primary airway mucin gene. The
calcium chloride-activated channel gene hCLCA1 (gob-5 in the mouse) has
been suggested to increase MUC-5AC gene expression, and both are increased
in asthmatic patients and murine models.
TNF-alpha increases the expression of these genes in vitro but has not been
investigated in vivo. OBJECTIVE: We sought to determine whether TNF-alpha
increases gene expression of gob-5 and MUC-5AC and induces
mucus cell metaplasia in vivo. METHODS: Naive
BALB/c mice received 50 ng of recombinant murine TNF-alpha (rmTNF-alpha)
intratracheally daily for 1, 2, or 3 weeks;
another group received the same dose of intratracheal
rmTNF-alpha daily for 3 weeks and then
alternate-day treatment for 3 additional weeks (total of 6 weeks). AKR mice
received 50 ng of rmTNF-alpha
intratracheally for 3 or 6 weeks daily. Naive nontreated mice were used as control animals. Airway
gene products for gob-5 and MUC-5AC were determined by means of real-time
PCR. Lung tissue sections were stained with periodic acid-Schiff/Alcian blue to assess mucus cell metaplasia.
RESULTS: rmTNF-alpha significantly increased gene
expression of airway gob-5 and MUC-5AC after 2 weeks in the BALB/c mice.
There was noticeable mucus staining in all mice treated for at least 3
weeks with TNF-alpha and in 80% of the mice receiving 2 weeks of treatment.
After 3 weeks of treatment, the AKR mice also showed increased gob-5
expression. CONCLUSIONS: This study demonstrates for the first time that
TNF-alpha alone in vivo is sufficient to increase airway mucus gene
expression in 2 murine strains.
PMID: 16337454 [PubMed - indexed for MEDLINE]
Metalloproteinases mediate mucin 5AC expression
by epidermal growth factor receptor activation.
Deshmukh
HS, Case LM, Wesselkamper
SC, Borchers
MT, Martin LD,
Shertzer
HG, Nadel
JA, Leikauf
GD.
Chronic obstructive pulmonary disease is marked by alveolar enlargement and
excess production of airway mucus. Acrolein, a
component of cigarette smoke, increases mucin 5AC
(MUC5AC), a prevalent airway mucin in NCI-H292
cells by transcriptional activation, but the signal transduction pathways involved
in acrolein-induced MUC5AC expression are
unknown. Acrolein depleted cellular glutathione
at doses of 10 muM or greater, higher than those
sufficient (0.03 muM) to increase MUC5AC mRNA,
suggesting that MUC5AC expression was independent of oxidative stress. In
contrast, acrolein increased MUC5AC mRNA levels
by phosphorylating epidermal growth factor
receptor (EGFR) and mitogen-activated protein kinase 3/2, or MAPK 3/2(ERK1/2). Pretreating
the cells with an EGFR-neutralizing antibody, or a metalloproteinase
inhibitor, decreased the acrolein-induced MUC5AC
mRNA increase. Small, interfering RNA directed against ADAM17 or MMP9
inhibited the acrolein-induced MUC5AC mRNA
increase. Acrolein increased the release and
subsequent activation of pro-MMP9. Acrolein
increased MMP9 and decreased tissue inhibitor of metalloproteinase 3
(TIMP3), an endogenous inhibitor of ADAM17, transcripts. Together, these
data suggest that acrolein induces MUC5AC
expression via an initial ligand-dependent
activation of EGFR mediated by ADAM17 and MMP9. In addition, a prolonged
effect of acrolein may be mediated by altering
MMP9 and TIMP3 transcription.
PMID: 15531749 [PubMed - indexed for MEDLINE]
[Expression of epidermal growth factor
receptor and MUC5AC on human airway with chronic obstructive pulmonary
disease]
[Article in Chinese]
Mao L, Bai
CX, Zhang M, Wang YH, Chen J.
Department of Pulmonary Diseases,
OBJECTIVE: To determine the relationship between epidermal growth factor
receptor (EGFR) expression and mucin 5AC (MUC5AC)
synthesis in human airways with chronic obstructive pulmonary disease
(COPD). METHODS: Lung specimens were obtained from 38 patients who were
undergoing lobectomy, and the samples were taken
from areas remote to the lesion. EGFR and MUC5AC protein expression were
examined using immunohistochemical analysis and
Western blot in peripheral airways (less than 2 mm in diameter) from 16
subjects with COPD, 10 subjects with a history of more than 30 pack-year
smoking and 12 nonsmokers or exsmokers (0 - 10
pack-year smoker). RESULTS: Weak EGFR protein signals were detected in the
lungs of the controls (2.01 +/- 1.02) in comparison with stronger signal in
the COPD patients (4.62 +/- 1.65, P < 0.01) and the smokers (4.89 +/-
1.89, P < 0.01). EGFR immunoreactivity was
observed mainly in goblet cells in the controls, the percentage of positive
cell being 71.1% +/- 14.3%, which was higher than those in COPD (21.1% +/-
8.6%) or in the smoker (21.9% +/- 9.7%) airways. In contrast, COPD or
smoker airways showed more expression of EGFR which expressed mainly in
basal cells (42.9% +/- 14.2%, 52.1% +/- 13.5%, respectively) than that in
the control airways (23.7% +/- 9.5%, P < 0.01). However there was no significant differences in EGFR expression and
location in peripheral airways between COPD patients and smokers (P >
0.05). There was significant positive correlation between EGFR immunoreactivity and the area of the MUC5AC positive staining
in all subjects (r = 0.877 4, P < 0.001). CONCLUSION: It is suggested
that EGFR activation is involved in mucin
expression in COPD airways.
PMID: 15498267 [PubMed - indexed for MEDLINE]
Moore
CR, Bishop GA.
Interdisciplinary Graduate Program in Immunology.
Engagement of CD40 on murine B cells by its ligand CD154 induces the binding of TNFR-associated
factors (TRAFs) 1, 2, 3, and 6, followed by the
rapid degradation of TRAFs 2 and 3. TRAF
degradation occurs in response to signaling by other TNFR superfamily members, and is likely to be a normal
regulatory component of signaling by this receptor family. In this study,
we found that receptor-induced TRAF degradation limits TRAF2-dependent CD40
signals to murine B cells. However, TRAFs 1 and 6 are not degraded in response to CD40
engagement, despite their association with CD40. To better understand the
mechanisms underlying differential TRAF degradation, mixed protein domain
TRAF chimeras were analyzed in murine B cells.
Chimeras containing the TRAF2 zinc (Zn) domains induced effective
degradation, if attached to a TRAF domain that binds to the PXQXT motif of
CD40. However, the Zn domains of TRAF3 and TRAF6 could not induce
degradation in response to CD40, regardless of the TRAF domains to which
they were attached. Our data indicate that TRAF2 serves as the master
regulator of TRAF degradation in response to CD40 signaling, and this
function is dependent upon both the TRAF Zn domains and receptor binding
position.
PMID: 16148124 [PubMed - in process]
Yang M, Hase
H, Legarda-Addison
D, Varughese
L, Seed B, Ting AT.
B cell maturation Ag (BCMA), a member of the TNFR superfamily
expressed on B cells, binds to a proliferation-inducing ligand
(APRIL) and B cell-activating factor of the TNF family (BAFF) but the
specific B cell responses regulated by BCMA remain unclear. This study
demonstrates that ligation of A20 B cells transfected with BCMA induces the expression of CD40,
CD80/B7-1, CD86/B7-2, MHC class II, and CD54/ICAM-1, which subsequently
enhances the presentation of OVA peptide Ag to DO11.10 T cells. BCMA
expression in murine splenic
B cells can be induced with IL-4 and IL-6, allowing subsequent treatment
with APRIL or agonist anti-BCMA to similarly induce Ag presentation. A
comparative analysis of hybrid receptors of TNFR2 fused to the cytoplasmic domains of APRIL/BAFF receptors found that
only BCMA, but not transmembrane activator and
calcium-modulator and cyclophilin ligand interactor or BAFF-R,
is capable of activating Ag presentation. Although all three receptors can
trigger NF-kappaB signaling, only BCMA activates
the JNK pathway conferring on BCMA the specific ability to activate this Ag
presentation response.
PMID: 16116167 [PubMed - in process]
Resveratrol suppresses IL-6-induced
Wung
BS, Hsu MC, Wu CC, Hsieh CW.
Department of Applied Microbiology,
Resveratrol, a polyphenolic
phytoaxelin present in red wine, has been
suggested to protect against atherosclerosis and cardiovascular disease
because of its antioxidant effects. Intercellular adhesion molecule
(ICAM-1), induced by cytokines, has been hypothesized to play a role in the
early events during atherosclerosis. In this study we tested the effects of
resveratrol upon both IL-6-induced ICAM-1 gene
expression and its underlying signaling pathways in endothelial cells (ECs). Resveratrol was found
to inhibit both TNFalpha- and IL-6-induced ICAM-1
gene expression at the promoter, transcriptional and protein levels. Resveratrol also abrogates the tyr705 phosphorylation of STAT3 in IL-6-treated ECs, in a dose- and time-dependent manner. Although quercetin had similar effects, resveratrol
showed higher inhibitory properties following 2-4 h pretreatments. Resveratrol has been shown to induce the activity of
endothelial nitric oxide synthase (eNOS) and increase NO production. Consistent with this,
the treatment of ECs with a NO donor (SNAP)
reduces IL-6-induced STAT3 phosphorylation.
Conversely, exposure of ECs to a NOS inhibitor
reversed the effects of resveratrol upon
IL-6-induced STAT3 phosphorylation. Furthermore, ECs transfected with
constitutively active Rac1 (RacV12) showed increases in ICAM-1 promoter
activity, intracellular reactive oxygen species (ROS) levels and STAT3 phosphorylation, and these increases were attenuated by
resveratrol treatment. In summary, we demonstrate
for the first time that resveratrol inhibits
IL-6-induced ICAM-1 gene expression, in part, by interfering with Rac-mediated pathways via the attenuation of STAT3 phosphorylation. This study therefore provides
important new insights that may contribute to the proposed beneficial
effects of resveratrol in endothelial responses
to cytokines during inflammation.
PMID: 16150460 [PubMed - as supplied by
publisher]