共查询到20条相似文献,搜索用时 413 毫秒
1.
Yeo Dae Yoon Eun Sook Lee Jong Pil Park Mee Ree Kim Jun Won Lee Tae Hoon Kim Min Kyun Na Jin Hee Kim 《Biotechnology and Bioprocess Engineering》2011,16(6):1099-1105
Hizikia fusiforme is a commonly used food that possesses potent anti-bacterial, anti-fungal, and anti-inflammatory activities. The immunostimulatory
activities of aqueous extract of Hizikia fusiforme (HFAE) in RAW 264.7 macrophages and whole spleen cells were investigated. HFAE activated RAW 264.7 macrophages to produce
cytokines such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in
a dose-dependent manner. In addition, HFAE induced the mRNA expression of TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophages.
Moreover, HFAE stimulated proliferation of whole spleen cells and reference mitogen. Taken together, the results demonstrate
that HFAE potently activates the immune function by regulating NO, TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophage and promoting
spleen cell proliferation. 相似文献
2.
Yao Z Qiu S Wang L Lu R Zhou CL Zhao PP Li HQ Gao WY 《Cancer immunology, immunotherapy : CII》2006,55(1):56-60
Tyroserleutide (YSL) is a type of active, low molecular weight polypeptide, comprised of three amino acids, which has antitumor
effects. YSL has various advantages over the other bioactive peptides such as its low molecular weight, simple construction,
nonimmunogenicity, specificity, few side effects, and ease of synthesis. However, the biological activities contributing to
it’s antitumor effects are not yet known. We studied the effects of YSL on the in vitro cytotoxic activity of BALB/c mice
peritoneal macrophages (PEMφ) against the target tumor cell lines BEL-7402 and B16-F10. We also measured the concentrations
of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and nitric oxide (NO) produced by YSL-activated Mφ, and we determined
the concentrations of IL-1β and NO secreted by YSL-activated murine macrophage RAW264.7 cells. YSL activated Mφ in vitro,
inhibited BEL-7402 proliferation, enhanced PEMφ antitumor effects, and stimulated IL-1β, TNF-α, and NO production by RAW264.7
cells. These data suggest that YSL activates the monocyte–macrophage system, which enhances Mφ antitumor effects against BEL-7402
and B16-F10 cells and stimulates the secretion by Mφ of cytotoxic effectors such as IL-1β, TNF-α, and NO. 相似文献
3.
4.
Iva Bozic Danijela Savic Danijela Laketa Ivana Bjelobaba Ivan Milenkovic Sanja Pekovic Nadezda Nedeljkovic Irena Lavrnja 《PloS one》2015,10(2)
Microglial cells are resident immune cells of the central nervous system (CNS), recognized as key elements in the regulation of neural homeostasis and the response to injury and repair. As excessive activation of microglia may lead to neurodegeneration, therapeutic strategies targeting its inhibition were shown to improve treatment of most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1 (thiamine) derivate exerting potentially anti-inflammatory effects. Despite the encouraging results regarding benfotiamine potential to alleviate diabetic microangiopathy, neuropathy and other oxidative stress-induced pathological conditions, its activities and cellular mechanisms during microglial activation have yet to be elucidated. In the present study, the anti-inflammatory effects of benfotiamine were investigated in lipopolysaccharide (LPS)-stimulated murine BV-2 microglia. We determined that benfotiamine remodels activated microglia to acquire the shape that is characteristic of non-stimulated BV-2 cells. In addition, benfotiamine significantly decreased production of pro-inflammatory mediators such as inducible form of nitric oxide synthase (iNOS) and NO; cyclooxygenase-2 (COX-2), heat-shock protein 70 (Hsp70), tumor necrosis factor alpha α (TNF-α), interleukin-6 (IL-6), whereas it increased anti-inflammatory interleukin-10 (IL-10) production in LPS stimulated BV-2 microglia. Moreover, benfotiamine suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and protein kinase B Akt/PKB. Treatment with specific inhibitors revealed that benfotiamine-mediated suppression of NO production was via JNK1/2 and Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and Akt pathways. Finally, the potentially protective effect is mediated by the suppression of translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus. Therefore, benfotiamine may have therapeutic potential for neurodegenerative diseases by inhibiting inflammatory mediators and enhancing anti-inflammatory factor production in activated microglia. 相似文献
5.
Maneb and paraquat are known to induce Parkinson’s disease (PD) phenotype, however, caffeine offers neuroprotection. Nitric
oxide (NO) acts an important mediator in PD phenotype and tyrosine kinase (TK), nuclear factor kappa B (NF-kB), p38 mitogen
activated protein kinase (p38 MAPK) are known to regulate its production. The present study aimed to elucidate the role of
caffeine in the regulation of NO production and microglial activation and their subsequent contribution in dopaminergic neuroprotection.
The animals were treated with caffeine and/or maneb and paraquat along with controls. In a few sets of experiments, the animals
were also treated with aminoguanidine, an inhibitor of inducible NO synthase, pyrrolidine dithiocarbamate (PDTC), an inhibitor
of NF-kB, genistein, an inhibitor of TK or SB202190, an inhibitor of p38 MAPK. Tyrosine hydroxylase (TH)-immunoreactivity
and anti-integrin αM (OX-42) staining were performed to assess the number of dopaminergic neurons and activation of microglia,
respectively. NO was measured in terms of nitrite, however, the expressions of p38 MAPK, interleukin (IL)-1β, NF-kB and TK
were checked by western blot analyses. Maneb and paraquat induced the number of degenerating dopaminergic neurons, microglial
cells, nitrite content, expressions of IL-1β, p38 MAPK, NF-kB and TK and caffeine co-treatment reduced the level of such alterations.
Reductions were more pronounced in the animals co-treated with aminoguanidine, PDTC, genistein or SB202190. The results obtained
thus demonstrate that caffeine down-regulates NO production, neuroinflammation and microglial activation, which possibly contribute
to neuroprotection. 相似文献
6.
7.
Beilei Lei Brian Mace Hana N. Dawson David S. Warner Daniel T. Laskowitz Michael L. James 《PloS one》2014,9(7)
Female sex is associated with improved outcome in experimental brain injury models, such as traumatic brain injury, ischemic stroke, and intracerebral hemorrhage. This implies female gonadal steroids may be neuroprotective. A mechanism for this may involve modulation of post-injury neuroinflammation. As the resident immunomodulatory cells in central nervous system, microglia are activated during acute brain injury and produce inflammatory mediators which contribute to secondary injury including proinflammatory cytokines, and nitric oxide (NO) and prostaglandin E2 (PGE2), mediated by inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. We hypothesized that female gonadal steroids reduce microglia mediated neuroinflammation. In this study, the progesterone’s effects on tumor necrosis factor alpha (TNF-α), iNOS, and COX-2 expression were investigated in lipopolysaccharide (LPS)-stimulated BV-2 microglia. Further, investigation included nuclear factor kappa B (NF-κB) and mitogen activated protein kinase (MAPK) pathways. LPS (30 ng/ml) upregulated TNF-α, iNOS, and COX-2 protein expression in BV-2 cells. Progesterone pretreatment attenuated LPS-stimulated TNF-α, iNOS, and COX-2 expression in a dose-dependent fashion. Progesterone suppressed LPS-induced NF-κB activation by decreasing inhibitory κBα and NF-κB p65 phosphorylation and p65 nuclear translocation. Progesterone decreased LPS-mediated phosphorylation of p38, c-Jun N-terminal kinase and extracellular regulated kinase MAPKs. These progesterone effects were inhibited by its antagonist mifepristone. In conclusion, progesterone exhibits pleiotropic anti-inflammatory effects in LPS-stimulated BV-2 microglia by down-regulating proinflammatory mediators corresponding to suppression of NF-κB and MAPK activation. This suggests progesterone may be used as a potential neurotherapeutic to treat inflammatory components of acute brain injury. 相似文献
8.
G. van Luijtelaar S. Lyashenko R. Vastyanov G. Verbeek A. Oleinik C. van Rijn G. Volokhova A. Shandra A. Coenen L. Godlevsky 《Neurophysiology》2012,43(6):478-486
We investigated the role of two cytokines, IL-1β and TNF-α, in the development of absence seizures using a genetic model of
absence epilepsy in WAG/Rij rats. We administered these cytokines to animals systemically and measured the number of spike-wave
discharges (SWDs) in the EEG. We also coadministered IL-1β with the GABA reuptake inhibitor tiagabine and measured the levels
of IL-1β and TNF-α in the brain and blood plasma of 2-, 4-, and 6-month-old WAG/Rij rats and animals that served as a non-epileptic
control (ACI). We found that IL-1β induced a significant increase in SWDs 2-5 h after administration, while TNF-α enhanced
SWDs much later. Both cytokines enhanced passive behavior; body temperature was elevated only after TNF-α. The action of tiagabine
was potentiated by earlier IL-1β injection, even when IL-1β was no longer active. Young WAG/Rij rats showed higher levels
of TNF-α in blood serum than young ACI rats; the effects in the brain tended to be opposite. The marked differences in timing
of the increase in SWDs suggest different time scales for the action of both cytokines tested. It is proposed that the results
found after TNF-α are due to the de novo synthesis of IL-1β. TNF-α may possess neuroprotective effects. IL-1β might increase GABA-ergic neurotransmission. The changes
in the efficacy of antiepileptic drugs related to changes in the cytokine systems may have some clinical relevance. 相似文献
9.
Nakaizumi A Horie T Kida T Kurimoto T Sugiyama T Ikeda T Oku H 《Cellular and molecular neurobiology》2012,32(1):95-106
Modulation of enzyme activity through nitrosylation has recently been identified as a new physiological activity of nitric
oxide (NO). We hypothesized that NO enhances the TNF-α-induced death of retinal neurons through a suppression of nuclear factor-κB
(NF-κB) by nitrosylation. In this study, cells from the RGC-5 line were exposed to different concentrations (2.0, 10, and
50 ng/ml) of TNF-α, and the degree of TNF-α-induced cell death was determined by the WST-8 assay and by flow cytometric measurements
of the externalization of phosphatidylserine. The effects of etanercept, a soluble TNFR-Fc fusion protein, and S-nitroso-N-penicillamine (SNAP), an NO donor, on the toxicity were determined. Experiments were also performed to determine whether
nitric oxide synthase (NOS) was associated with the toxicity of TNF-α. The activation of NF-κB was determined by the detection
of the p65 subunit in the nuclear extracts. Our results showed that exposure of RGC-5 cells to different concentrations of
TNF-α significantly decreased the number of living cells in a dose-dependent way. The death was partially due to apoptosis
with an externalization of phosphatidylserine, and the death was suppressed by etanercept. Exposure to TNF-α increased the
activation of NF-κB and the expression of iNOS. Although NF-κB inhibitors suppressed the increase of iNOS, they also potentiated
the TNF-α-induced death. Both L-NAME and aminoguanidine, both NOS inhibitors, rescued the cells from death. In contrast, addition
of SNAP caused nitrosylation of the inhibitory κB kinase, and suppressed the NF-κB activation and potentiated the TNF-α-induced
neurotoxicity. These results indicate that NO potentiates the neurotoxicity of TNF-α by suppressing NF-κB. 相似文献
10.
Núria Gresa-Arribas Cristina Viéitez Guido Dentesano Joan Serratosa Josep Saura Carme Solà 《PloS one》2012,7(9)
Neuron-microglia co-cultures treated with pro-inflammatory agents are a useful tool to study neuroinflammation in vitro, where to test the potential neuroprotective effect of anti-inflammatory compounds. However, a great diversity of experimental conditions can be found in the literature, making difficult to select the working conditions when considering this approach for the first time. We compared the use of neuron-primary microglia and neuron-BV2 cells (a microglial cell line) co-cultures, using different neuron:microglia ratios, treatments and time post-treatment to induce glial activation and derived neurotoxicity. We show that each model requires different experimental conditions, but that both neuron-BV2 and neuron-primary microglia LPS/IFN-γ-treated co-cultures are good to study the potential neuroprotective effect of anti-inflammatory agents. The contribution of different pro-inflammatory parameters in the neurotoxicity induced by reactive microglial cells was determined. IL-10 pre-treatment completely inhibited LPS/IFN-γ-induced TNF-α and IL-6 release, and COX-2 expression both in BV2 and primary microglial cultures, but not NO production and iNOS expression. However, LPS/IFN-γ induced neurotoxicity was not inhibited in IL-10 pre-treated co-cultures. The inhibition of NO production using the specific iNOS inhibitor 1400 W totally abolished the neurotoxic effect of LPS/IFN-γ, suggesting a major role for NO in the neurotoxic effect of activated microglia. Consequently, among the anti-inflammatory agents, special attention should be paid to compounds that inhibit NO production. 相似文献
11.
12.
Over activation of microglia results in the production of proinflammatory agents that have been implicated in various brain diseases. Pycnogenol is a patented extract from French maritime pine bark (Pinus pinaster Aiton) with strong antioxidant and anti-inflammatory potency. The present study investigated whether pycnogenol may be associated with the production of proinflammatory mediators in lipopolysaccharide-stimulated BV2 (mouse-derived) microglia. It was found that pycnogenol treatment was dose-dependently associated with significantly less release of nitricoxide (NO), TNF-α, IL-6 and IL-1β, and lower levels of intercellular adhesion molecule1 (ICAM-1) and perilipin 2 (PLIN2). Furthermore, this effect was replicated in primary brain microglia. Levels of inducible NO synthase mRNA and protein were attenuated, whereas there was no change in the production of the anti-inflammatory cytokine IL-10. Further evidence indicated that pycnogenol treatment led to the suppression of NF-κB activation through inhibition of p65 translocation into the nucleus and inhibited DNA binding of AP-1, suggesting that these proinflammatory factors are associated with NF-κB and AP-1. We conclude that pycnogenol exerts anti-inflammatory effects through inhibition of the NF-κB and AP-1pathway, and may be useful as a therapeutic agent in the prevention of diseases caused by over activation of microglia. 相似文献
13.
Fei Guo Xiang Guo An Xie Yuan Lei Lou Yang Wang 《Biological trace element research》2011,142(3):693-703
Lanthanide ions have been proven to have various biologic effects. Lanthanum with extremely active physical and chemical property
was evidenced to possess antibacterial and immune adjustment effects. In the present study, the anti-inflammatory effects
of lanthanum chloride (LaCl3) on lipopolysaccharide (LPS)-challenged mice were examined in vivo and in vitro. The results indicated that LaCl3 can greatly decrease the secretion of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β as well as TNF-α mRNA expression
in the mice challenged with LPS. To clarify the mechanism involved, the effects of LaCl3 on the activation of nuclear factor (NF)-κB were examined both in liver and in peritoneal macrophages. The LPS-induced activation
of NF-κB was significantly blocked by LaCl3. These findings demonstrate that the inhibition of the LPS-induced inflammatory media, such as TNF-α and IL-1β, by LaCl3, is due to the inhibition of NF-κ B activation. 相似文献
14.
Protective effects of an anti-inflammatory cytokine, interleukin-4, on motoneuron toxicity induced by activated microglia 总被引:1,自引:0,他引:1
Microglia-mediated cytotoxicity has been implicated in models of neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease, but few studies have documented how neuroprotective signals might mitigate such cytotoxicity. To explore the neuroprotective mechanism of anti-inflammatory cytokines, we applied interleukin-4 (IL-4) to primary microglial cultures activated by lipopolysaccharide as well as to activated microglia cocultured with primary motoneurons. lipopolysaccharide increased nitric oxide and superoxide (O(2) (.-)) and decreased insulin-like growth factor-1 (IGF-1) release from microglial cultures, and induced motoneuron injury in microglia-motoneuron cocultures. However, lipopolysaccharide had minimal effects on isolated motoneuron cultures. IL-4 interaction with microglial IL-4 receptors suppressed and nitric oxide release, and lessened lipopolysaccharide-induced microglia-mediated motoneuron injury. The extent of nitric oxide suppression correlated directly with the extent of motoneuron survival. Although IL-4 enhanced release of free IGF-1 from microglia in the absence of lipopolysaccharide, it did not enhance free IGF-1 release in the presence of lipopolysaccharide. These data suggest that IL-4 may provide a significant immunomodulatory signal which can protect against microglia-mediated neurotoxicity by suppressing the production and release of free radicals. 相似文献
15.
Tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β) genetic variants which resulting in TNF-α and IL-1 overproduction
may increase susceptibility to autoimmune diseases such as atherosclerosis. We have studied the association of TNF-α G308A
and IL-1β (+3953) C/T polymorphism with myocardial infarction in Turkish population. 143 patients with myocardial infarction
and 213 age-matched healthy controls were included in the study. In univariant analysis, the frequencies of IL-1β, TNF-α genotype
or allele, and haplotype of C:A and T:A were significantly elevated in patients when compared with those of controls. GA genotype
of TNF-α, T allele of IL-1β and A of TNF-α allele seem to be risk factors for myocardial infarction. In contrast, CC genotype
of IL-1β and GG genotype of TNF-α have protective effect against myocardial infarction. In multivariate logistic regression
analysis, TNF-α A allele, gender and smoking were associated with myocardial infarction. In conclusion, we can state that
TNF-α A allele might be associated with myocardial infarction. 相似文献
16.
The capacity of cornel iridoid glycoside (CIG) to suppress the manifestations of ischemic stroke was investigated. CIG was
administered to rats by the intragastric route once daily for 7 days. Focal cerebral ischemia was induced by 2 h of middle
cerebral artery occlusion followed by 24 h of reperfusion. In non-treated rats large infarct areas were observed within 24 h
of reperfusion. Examination of the ischemic cerebral cortex revealed microglia and astrocyte activation, increased interleukin-1β
(IL-1 β) and tumor necrosis factor-α (TNF-α) concentrations, increased DNA fragmentation in the ischemia penumbra, elevated
Bax expression, increased caspase-3 cleavage, and decreased Bcl-2 expression. Pretreatment with CIG decreased the infarct
area, DNA fragmentation, IL-1β and TNF-α concentrations, microglia and astrocyte activation, Bax expression, and caspase-3
cleavage while increasing Bcl-2 expression. CIG exerts anti-neuroinflammatory and anti-apoptotic effects which should prove
beneficial for prevention or treatment of stroke. 相似文献
17.
Danielle Burger 《Arthritis research & therapy》2000,2(6):472-5
The intricate interactions that regulate relationships between endogenous tissue cells and infiltrating immune cells in the rheumatic joint, particularly in rheumatoid arthritis (RA), were the subject of the meeting. A better understanding of these interactions might help to define intervention points that could be used to develop specific therapies. The presentations and discussions highlighted the fact that, once chronic inflammation is established, several pro-inflammatory loops involving tumour necrosis factor (TNF)-α and interleukin (IL)-1β can be defined. Direct cellular contact with stimulated T lymphocytes induces TNF-α and IL-1β in monocytes which in turn induce functions in fibroblast-like synoviocytes. The latter include the production of stromal cell-derived factor-1α (SDF-1α) which enhances the expression of CD40L in T cells, which stimulates SDF-1α production in synoviocytes, which in turn protects T and B cells from apoptosis and enhances cell recruitment thus favoring inflammatory processes. IL-1β and TNF-α also induce IL-15 in fibroblast-like synoviocytes, which induces the production of IL-17 which in turn potentiates IL-1β and TNF-α production in monocyte-macrophages. This underlines the importance of TNF-α and IL-1β in RA pathogenesis, and helps explain the efficiency of agents blocking the activity of these cytokines in RA. Factors able to block the induction of cytokine production (such as apolipoprotein A-I [apo A-I] and interferon [IFN]-β) might interfere more distally in the inflammatory process. Furthermore, stimulated T lymphocytes produce osteoclast differentiation factor (ODF), which triggers erosive functions of osteoclasts. Therefore, factors capable of affecting the level of T lymphocyte activation, such as IFN-β, IL-15 antagonist, or SDF-1α antagonist, might be of interest in RA therapy. 相似文献
18.
19.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):954-959
Microglial activation has been associated with neurodegenerative diseases by inducing the neuroinflammatory mediators such as nitric oxide (NO), TNF-α and IL-1β. (?)-Nyasol, a norlignan isolated from a medicinal plant Anemarrhena asphodeloides, showed anti-inflammatory potential in lipopolysaccharide (LPS)-activated BV-2 microglial cells. (?)-Nyasol inhibited the production of NO and prostaglandin E2 (PGE2) and also the expression of inducible nitric oxide synthase and cyclooxygenase-2, which are responsible for the respective production of NO and PGE2. It also suppressed the mRNA levels of TNF-α and IL-1β in activated microglial cells. These effects of (?)-nyasol were correlated with the inactivation of p38 MAPK and the suppression of LPS-induced I-κBα degradation. Taken together, these results suggest that (?)-nyasol can be a modulator in neuroinflammatory conditions induced by microglial activation. 相似文献
20.
Ethyl acetate extracts of alfalfa (Medicago sativa L.) sprouts inhibit lipopolysaccharide-induced inflammation in vitro and in vivo 总被引:1,自引:0,他引:1
Yong-Han Hong Wen-Wan Chao Miaw-Ling Chen Bi-Fong Lin 《Journal of biomedical science》2009,16(1):64-12
This study aimed to investigate if food components that exert anti-inflammatory effects may be used for inflammatory disorders
by examining alfalfa sprout ethyl acetate extract (ASEA). The cytokine profile and life span of BALB/c mice with acute inflammation
after intra-peritoneal (ip) injection of 15 mg/kg BW lipopolysaccharide (LPS) were determined. The results showed that the
life span of LPS-induced inflammatory mice were negatively correlated with serum levels of TNF-α, IL-6, and IL-1β at 9 hr
after LPS-injection, which indicated that suppressing these cytokines in the late phase of inflammation may be beneficial
for survival. The in vitro experiment then showed that ASEA significantly reduced IL-6 and IL-1β production and the NF-κB trans-activation activity
of mitogen-stimulated RAW264.7 cells. To further evaluate the anti-inflammatory effects of ASEA in vivo, BALB/c mice were tube-fed with 25 mg ASEA/kg BW/day in 50 μl sunflower oil, while the control and PDTC (pyrrolidine dithiocarbamate,
an anti-inflammatory agent) groups were tube-fed with 50 μl sunflower oil/day only. After one week of tube-feeding, the PDTC
group was injected with 50 mg/kg BW PDTC and one hour later, all of the mice were injected with 15 mg/kg BW LPS. The results
showed that the ASEA and PDTC groups had significantly lower serum TNF-α, IL-6, and IL-1β levels at 9 hr after LPS challenge,
and significantly higher survival rates than the control group. This study suggests that ASEA supplementation can suppress
the production of pro-inflammatory cytokines and alleviate acute inflammatory hazards. 相似文献