共查询到20条相似文献,搜索用时 31 毫秒
1.
Hong-Mei Wang Ting Zhang Qiang Li Jian-Kang HuangRong-Fu Chen Xiao-Jiang Sun 《Neurochemistry international》2013
An increasing amount of evidence has emerged to suggest that neuroinflammatory process is involved in the pathogenesis of Parkinson’s disease (PD). Activated microglia and astrocytes are found in the substantia nigra (SN) of Parkinson’s disease brains as well as in animal models of Parkinson’s disease. Although reactive astrocytes are involved in the progression of PD, the role of reactive astrocytes in neuroinflammation of PD has received limited attention to date. Recently, Glycogen synthase kinase-3β (GSK-3β) was identified as a crucial regulator of the inflammatory response. The purpose of this study was to explore the mechanism by which 6-hydroxydopamine (6-OHDA) induces inflammatory response in astrocytes and observe the anti-inflammatory effect of lithium chloride (LiCl) on 6-OHDA-treated astrocytes. 相似文献
2.
Our work aimed to provide a topographical analysis of all known ionotropic P2X1–7 and metabotropic P2Y1,2,4,6,11–14 receptors that are present in vivo at the protein level in the basal ganglia nuclei and particularly in rat brain slices
from striatum and substantia nigra. By immunohistochemistry-confocal and Western blotting techniques, we show that, with the
exception of P2Y11,13 receptors, all other subtypes are specifically expressed in these areas in different amounts, with ratings of low (P2X5,6 and P2Y1,6,14 in striatum), medium (P2X3 in striatum and substantia nigra, P2X6,7 and P2Y1 in substantia nigra) and high. Moreover, we describe that P2 receptors are localized on neurons (colocalizing with neurofilament
light, medium and heavy chains) with features that are either dopaminergic (colocalizing with tyrosine hydroxylase) or GABAergic
(colocalizing with parvalbumin and calbindin), and they are also present on astrocytes (P2Y2,4, colocalizing with glial fibrillary acidic protein). In addition, we aimed to investigate the expression of P2 receptors
after dopamine denervation, obtained by using unilateral injection of 6-hydroxydopamine as an animal model of Parkinson’s
disease. This generates a rearrangement of P2 proteins: most P2X and P2Y receptors are decreased on GABAergic and dopaminergic
neurons, in the lesioned striatum and substantia nigra, respectively, as a consequence of dopaminergic denervation and/or
neuronal degeneration. Conversely, P2X1,3,4,6 on GABAergic neurons and P2Y4 on astrocytes augment their expression exclusively in the lesioned substantia nigra reticulata, probably as a compensatory
reaction to dopamine shortage. These results disclose the presence of P2 receptors in the normal and lesioned nigro-striatal
circuit, and suggest their potential participation in the mechanisms of Parkinson’s disease. 相似文献
3.
In the peripheral nervous system (PNS), tumor necrosis factor-alpha (TNF-α) derived from activated Schwann cells (SCs) play
a critical role as a pleiotropic mediator. In this study, we examined the function of TNF-α as an inflammatory mediator in
SCs activation. TNF-α exhibits its biological effect through two distinct surface receptors, TNF receptor 1 (TNFR1) and TNFR2.
We show here that cultured SCs express both TNFR1 and TNFR2, and that activation of these receptors by TNF-α promotes expression
of TNF-α. Meanwhile, TNF-α also increased the production of other inflammatory mediators. Furthermore, TNF-α is involved in
the induction of apoptosis through binding to TNFR in SCs. The activation of SCs by lipopolysaccharide (LPS) is partially
mediated by SCs-derived TNF-α. These findings suggest the existence of a positive feedback loop in the activation of SC via
TNF-α. This loop may be involved in the prolonged activation of SCs. Acute or chronic stimulation of TNF-α by SC at sites
of PNS inflammation may be critical in determining whether TNF-α has activational, inflammatory, or cytotoxic effects on these
cells.
Yongwei Qin and Chun Cheng contributed equally to this work. 相似文献
4.
P38 mitogen-activated protein kinases (p38 MAPK) and tumor necrosis factor-α (TNF-α) play important roles in oxidative stress-induced
apoptosis in cardiac myocytes. However, the regulation and functional role of cross-talk between p38 MAPK and TNF-α pathways
have not yet been fully characterized in cardiac myocytes. In this study, we found that inhibition of p38 MAPK with SB-203580
(SB) reduced H2O2-stimulated secretion of TNF-α, whereas pre-activation of p38 MAPK with sodium arsenite (SA) enhanced H2O2-stimulated secretion of TNF-α. In addition, pretreatment of cells with TNF-α increased basal and H2O2-stimulated p38 MAPK and apoptosis of cardiac myocytes, and p38 MAPK-associated apoptosis of cardiac myocytes induced by TNF-α
was blocked by inhibition of p38 MAPK with SB. Finally, H2O2-induced apoptosis was attenuated by the inhibitors of p38 MAPK or reactive oxygen species (ROS), whereas it was enhanced
by p38 MAPK agonist SA. These results suggest that H2O2-induced secretion of TNF-α increases apoptosis of cardiac myocytes through ROS-dependent activation of p38 MAPK. This may
represent a novel mechanism that TNF-α partly interplays with p38 MAPK pathways during oxidative stress-modulated apoptosis
in cardiac myocytes. 相似文献
5.
β-1,4-galactosyltransferase I (β-1,4-GalT I) plays an important role in the synthesis of the backbone structure of adhesion molecules involved in leukocyte–endothelial
cell interaction. The expression of β-1,4-GalT I mRNA increased in primary human endothelial cells after exposure to tumor necrosis factor-α (TNF-α). In the central nervous system (CNS), astrocytes play a pivotal role in immunity as immunocompetent cells by secreting
cytokines and inflammatory mediators, there are two types of astrocytes. Type-1 astrocytes can secrete TNF-α when stimulated
with Lipopolysaccharide (LPS), while the responses of type-2 astrocytes during inflammation are unknown. So we examined the
expression change of β-1,4-GalT I mRNA in type-2 astrocytes after exposure to TNF-α and LPS. Real-time PCR showed that TNF-α or LPS affected β-1,4-GalT I mRNA expression in a time- and dose-dependent manner. RT-PCR analysis revealed that TNFR1 and TNFR2 were present
in normal untreated type-2 astrocytes, and that TNF-α, TNFR1 and TNFR2 increased in type-2 astrocytes after exposure to TNF-α or LPS. Immunocytochemistry showed that TNFR1 was
expressed in the cytoplasm, nucleus and processes of normal untreated type-2 astrocytes, and distributed mainly in the cytoplasm
and processes after exposure to LPS. TNFR2 was mainly expressed in the nucleus of normal untreated type-2 astrocytes, and
distributed mainly in the processes of type-2 astrocytes after exposure to LPS. Both anti-TNFR1 and anti-TNFR2 antibodies
suppressed β-1,4-GalT I mRNA expression induced by TNF-α or LPS. From these results, we conclude that TNF-α signaling via both TNFR1 and TNFR2 translocated from nucleus to cytoplasm or processes is sufficient to induce β-1,4-GalT I mRNA. In addition, we observed that not only exogenous TNF-α but also TNF-α produced by type-2 astrocytes affected β-1,4-GalT I mRNA production in type-2 astrocytes. These results suggest that an autocrine loop involving TNF-α contributes
to the production of β-1,4-GalT I mRNA in response to inflammation.
Chunlin Xia is the co-first author. 相似文献
6.
α-Synuclein plays a key role in the pathological neurodegeneration in Parkinson’s disease. Although its contribution to normal
physiology remains elusive, the selective degeneration of α-synuclein-containing dopaminergic neurons in Parkinson’s disease
may be linked to abnormal α-synuclein induced toxicity. In the present study, a complex of α-synuclein and vesicular monoamine
transporter-2 was identified by GST-Pull Down experiment. In wild-type α-synuclein stably transfected SH-SY5Y cell lines,
the activity of vesicular monoamine transporter-2 decreased by 31% as determined by [3H] dopamine uptake, and its expression also decreased in both protein and mRNA levels using western and northern blot analysis.
Overexpression of wild-type α-synuclein did not induce cell death or apoptosis, but significantly enhanced the intracellular
reactive oxygen species level as assayed by flow cytometry. These data suggest that Up-regulated α-synuclein expression inhibits
the activity of vesicular monoamine transporter-2, thereby interrupting dopamine homeostasis and resulting in dopaminergic
neuron injury in Parkinson’s disease. 相似文献
7.
8.
Preciado-Patt Liana Cahalon Liora Hershkovitz Rami Lider Ofer Pras Mordechai Fridkin Mati 《International journal of peptide research and therapeutics》1998,5(5-6):349-355
Summary Serum amyloid A (SAA), an acute-phase reactant, exists naturally as a minor protein in the sera of healthy individuals. However,
its levels in sera are increased markedly during various transient and chronic inflammatory diseases, often concomitantly
with accumulation at inflicted sites. SAA is synthesized mainly in the liver following the synergistic action of cytokines,
mainly tumor necrosis factor-α (TNF-α) and interleukin-1 and-6 (IL-1 and IL-6). It was already shown by us that upon interaction
with SAA or amyloid A (AA), the extracellular matrix (ECM) and laminin induced the adhesion of resting human CD4+ T-cells in an apparently β1-integrin-mediated manner. Herein we have shown that the SAA-ECM complex modulates the regulation of cytokine synthesis by
human T-lymphocytes. The SAA-ECM complex dramatically enhanced the release of TNF-α by human T-cells in a dose-dependent manner,
reaching its maximal effect in the presence of 100 μM recombinant SAA. The SAA domain, responsible for the enhanced release
of TNF-α by human T-lymphocytes, is apparently the amyloid A protein (AA, i.e. SAA2-82). Specifically, TNF-α enhanced secretion
is mediated through intimate interactions of SAA/AA, with laminin. Thus, the ECM serving as a temporary anchorage site for
SAA and AA seems to be involved in regulating TNF-α secretion and the recruitment and accumulation of immunocytes in extravascular,
inflammatory compartments. 相似文献
9.
10.
Shen A Chen J Qian J Zhu J Hu L Yan M Zhou D Gao Y Yang J Ding F Cheng C 《Glycoconjugate journal》2009,26(1):19-31
β1,4-Galactosyltransferase-I (β1,4-GalT-I) is one of the best studied glycosyltransferases. Previous studies demonstrated
that β1,4-GalT-I was a major galactosyltransferase responsible for selectin-ligand biosynthesis and that inflammatory responses
of β1,4-GalT-I deficient mice were impaired. In this study, we investigate the expression of β1,4-GalT-I in lipopolysaccharide
(LPS)-induced neuroinflammatory processes. The results of this study demonstrated that β1,4-GalT-I was strongly induced by
intraspinal administration of LPS. More than 90% galactose-containing glycans and β1,4-GalT-I were expressed in immune cells.
The ELISA assay shows focal injection LPS also induces TNF-α alteration. Double staining indicated β1,4-GalT-I overlapped
with TNF-α. Moreover, RT-PCR for β1,4-GalT-I mRNA showed that β1,4-GalT-I mRNA in microglia in vitro was affected in a dose- and time dependent manner in response to LPS or TNF-α stimulation. All these results indicated that
the increase of β1,4-GalT-I might attribute to the effect of TNF-α excreting during inflammation. E-selectin, which ligand
was modified by β1,4-GalT-I, was correlated with galactose-containing glycans following injecting LPS into spinal cord. We
therefore suggest that β1,4-GalT-I may play an important role in regulating immune cell migration into the inflammatory site.
Aiguo Shen and Jianping Chen contributed equally to this work. 相似文献
11.
An intimate interplay exists between the bone and the immune system, which has been recently termed osteoimmunology. The activity
of immune cells affects the intrinsic balance of bone mineralization and resorption carried out by the opposing actions of
osteoblasts and osteoclasts. The aim of this study was to determine the possible interaction between inflammatory-induced
conditions and matrix metalloproteinases-2,-9 (MMP-2,-9) synthesis and secretion by bone marrow-derived osteoprogenitor cells
during advanced stages of osteogenesis. Rat bone marrow-derived mesenchymal stem cells (MSCs) were cultured in the presence
of osteogenic supplements in order to direct the cells towards the osteogenic differentiation lineage. At the late stages
of osteogenesis, assessed by histochemistry, immunohistochemistry and RT-PCR, cultures were exposed to pro-inflammatory cytokines,
tumor necrosis factor-alpha (TNF-α) and interleukin-1alpha (IL-1α). Biochemical, histochemical and molecular biology techniques
were used to discern the influence of pro-inflammatory cytokines on MMP-2,-9 synthesis and secretion. Results indicated that
MMP-9 synthesis and secretion were significantly induced after exposure to the cytokines (TNF-α, IL-1α) treatment, while MMP-2
levels remained unchanged. These results indicate that in response to inflammatory processes, osteoblasts, in addition to
osteoclasts, can also be involved and contribute to the process of active bone resorption by secretion and activation of MMPs. 相似文献
12.
de Souza LF Gelain DP Jardim FR Ribeiro GR Zim M Bernard EA 《Molecular and cellular biochemistry》2006,281(1-2):123-128
Recent reports have described purinergic modulation of tumor necrosis factor-alpha (TNF-α) signaling in neutrophils and astrocytes.
In Sertoli cells, both TNF-R1 and TNF-R2 TNF-α receptors are present and this cytokine modulates many functions of these cells
related to the maintenance of spermatogenesis. Sertoli cells express distinct purinoreceptors and previous work has shown
that these cells secrete extracellular nucleotides and their metabolites. In this work, we studied the possible role of extracellular
purines in TNF-α signaling in cultured Sertoli cells. This cytokine increased inosine concentration from 30 min to 6 h, with
no effect at 24 h. Both TNF-α and inosine increased nitrite accumulation and nitric oxide synthase activity. Erythro-9-(2-hydroxy-3-nonyl)adenine
(EHNA), an adenosine deaminase inhibitor, abolished the TNF-α induced inosine increase, nitrite accumulation and nitric oxide
synthase activity. These results suggest that extracellular inosine acts as intermediary in TNF-α stimulated nitric oxide
production in cultured Sertoli cells. 相似文献
13.
14.
15.
Soluble human tumor necrosis factor receptors (shTNFRI and shTNFRII) are antagonists of tumor necrosis factor-α (TNF-α) and
are under clinical investigation as therapy for autoimmune diseases and transplant rejection. However, shTNFRI and shTNFRII
are limited for clinical usage because of their short half-lives in vivo. Recombinant TNF-α receptors (infliximab and etanercept)
are used in treatment of rheumatoid arthritis and Crohn’s disease but are also being tested for a number of other autoimmune
diseases. Human serum albumin (HSA) has been used to construct long-acting fusion proteins. Here, we report the effect of
fusion of HSA with shTNFRI and with shTNFRII on shTNFR’s neutralizing activity against TNF-α. HSA fusion proteins were separately
expressed in Pichia pastoris. Purified recombinant shTNFRI-HSA, HSA-shTNFRI and HSA-shTNFRII could block the cytolytic activity of TNF-α in L929 cells,
and the fusion at N-terminus of shTNFRI could result in larger degree of activity decline than that at the C-terminus. Activity of three fusion proteins was much weaker than etanercept, which demonstrated that fusion of HSA significantly
influenced TNF-α neutralizing activity of shTNFRs. Compared with Fc fragment, HSA fusion technology may therefore not be an
ideal strategy in development of long-acting shTNFRs protein drugs. 相似文献
16.
Tumor necrosis factor-α (TNF-α) plays an important role in pathological angiogenesis associated with inflammatory response.
Pim-3 kinase belonging to serine/threonine protein kinases is a potent suppressor of myc-induced apoptosis. We have recently
demonstrated that Pim-3 plays an essential role in endothelial cell (EC) spreading and migration. In this study, we showed
that TNF-α transiently increased Pim-3 mRNA expression, and this was mediated through Tumor necrosis factor-α receptor-1 (TNFR1)
pathway in ECs. TNF-α could promote stabilization of Pim- 3 mRNA in ECs. Small-interfering RNA (siRNA)-mediated gene knockdown
of Pim-3 significantly impaired TNF-α-induced formation of EC membrane protrusions in vitro. Furthermore, Pim-3 silencing inhibited EC sprouting in subcutaneous Matrigel in vivo. eNOS mRNA abundance was lower in Pim-3 siRNA transfected ECs compared with the control ECs. These observations suggest that
Pim-3 plays a role in TNF-α-induced angiogenesis. 相似文献
17.
Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) affect a large percent of the population worldwide. Experimental
studies have revealed that T2DM and AD share several molecular processes that underlie their respective degenerative pathology.
Based on this information, we quantified TNF-α, IL-6 levels, serum glucose, serum triglyceride, hepatic triglyceride, serum
AST, serum ALT and butyrylcholinesterase (BuChE) in various rat tissues. HFD was fed to rats resulting in increased body weight,
fasting blood glucose, IL-6, TNF-α levels, hepatic triglyceride, serum AST, serum ALT and BuChE. SK0506 treatment significantly
prevented weight gain induced by HFD feeding. SK0506, but not Rosiglitazone, significantly reduced serum and hepatic triglycerides
levels. Treatment with SK0506 also ameliorated elevated levels of both inflammatory markers (TNF-α and IL-6) and serum liver
enzymes (ALT and AST) significantly in HFD fed rats. BuChE activity also reduced in skeletal muscle and adipose tissues of
rats treated by SK0506. In conclusion, current study has opened new potential avenues towards research for management of T2DM
and AD by Chinese herbal extracts, “SK0506”. 相似文献
18.
Neuronal apoptosis in neurodegenerative diseases is correlated with inflammatory reactions. The beneficial or detrimental
role of apoptosis in neuroinflammation is unclear. In this study, we injected β-amyloid peptide into the rat cortex for induction
of neuroinflammation in hippocampus. We observed an increase in TNF-α as an inflammatory cytokine and caspase3 and TUNEL-positive
cells as apoptotic marker. As far as ability of TNF-α to induce apoptosis or activate NF-kβ, the question is what will happen
if the balance between two pathways is disturbed by inhibition of apoptosis. Using caspase inhibitors, we inhibited apoptosis
and assessed NF-kβ, Hsp 70 (a hallmark of cancer), cmyc (proto-oncogene) and p53 (tumor suppressor protein). There was an
unexpected decrease in NF-kβ while Hsp70 and cmyc upregulated and p53 decreased. These results imply that inhibition of apoptosis
due to increased susceptibility to abnormal mitosis may not provide a reliable strategy for treatment of neuroinflammatory
diseases. 相似文献
19.
α-Synuclein and dopamine metabolism 总被引:4,自引:0,他引:4
α-Synuclein (α-Syn), a 140-amino-acid protein richly expressed in presynaptic terminals in the central nervous system, has
been shown to play a central role in the pathogenesis of Parkinson’s disease. Although the normal functions of α-Syn remain
elusive, accumulating evidence shows that the molecule is involved in multiple steps related to dopamine metabolism, including
dopamine synthesis, storage, release, and uptake. The regulatory effect of α-Syn on dopamine metabolism is likely to tone
down the amount of cytoplasmic dopamine at nerve terminals, thereby limiting its conversion to highly reactive oxidative molecules.
Formation of α-Syn protofibrils triggered by factors such as gene mutations and environmental toxins can make the molecule
lose its normal functions, leading to disrupted homeostasis of dopamine metabolism, increased cytoplasmic dopamine levels,
and enhanced oxidative stress in dopaminergic neurons. The enhanced oxidative stress will, in turn, exacerbate the formation
of α-Syn protofibrils and drive the neurons into a vicious cycle, which will finally result in the selective degeneration
of the dopaminergic neurons associated with Parkinson’s disease. 相似文献
20.
S. J. D. Vitkus S. A. Hanifin D. W. McGee 《In vitro cellular & developmental biology. Animal》1998,34(8):660-664
Summary Intestinal epithelial cells (IEC) have previously been shown to produce several cytokines including interleukin-6 (IL-6).
However, many factors which may regulate IL-6 secretion by human IEC still remain a mystery due in part to the lack of appropriate
model cell lines and the difficulty of culturing human IEC over long periods of time. We have determined that the human colonic
carcinoma cell line Caco-2 is capable of secreting IL-6 when stimulated by the inflammatory cytokines IL-1β or tumor necrosis
factor-α (TNF-α), and stimulation of these cells with IL-1β plus TNF-α induced a synergistic enhancement of IL-6 secretion.
The inflammatory cytokine-induced enhancement in IL-6 secretion was greatest when the cells were cultured in a 10% CO2 atmosphere as compared to cells grown in 5% CO2, suggesting that environmental CO2 levels may affect IEC cytokine secretion. Finally, long-term culture of the Caco-2 cells to induce cellular differentiation
had no effect on the capacity of these cells to produce IL-6, indicating that the regulation of IL-6 secretion was not affected
by differentiation. Taken together, these studies provide important information on the factors which regulate IL-6 secretion
by human IEC as they may contribute to the cytokine network during a mucosal inflammation. The results also suggest that the
Caco-2 cell line is an appropriate model for further studies on the regulation of cytokine secretion by human IEC. 相似文献