共查询到20条相似文献,搜索用时 31 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.
Hirofumi Shoda Keishi Fujio Yumi Yamaguchi Akiko Okamoto Tetsuji Sawada Yuta Kochi Kazuhiko Yamamoto 《Arthritis research & therapy》2007,8(6):R166
IL-32 is a newly described cytokine in the human found to be an in vitro inducer of tumor necrosis factor alpha (TNFα). We examined the in vivo relationship between IL-32 and TNFα, and the pathologic role of IL-32 in the TNFα-related diseases – arthritis and colitis.
We demonstrated by quantitative PCR assay that IL-32 mRNA was expressed in the lymphoid tissues, and in stimulated peripheral
T cells, monocytes, and B cells. Activated T cells were important for IL-32 mRNA expression in monocytes and B cells. Interestingly,
TNFα reciprocally induced IL-32 mRNA expression in T cells, monocyte-derived dendritic cells, and synovial fibroblasts. Moreover,
IL-32 mRNA expression was prominent in the synovial tissues of rheumatoid arthritis patients, especially in synovial-infiltrated
lymphocytes by in situ hybridization. To examine the in vivo relationship of IL-32 and TNFα, we prepared an overexpression model mouse of human IL-32β (BM-hIL-32) by bone marrow transplantation.
Splenocytes of BM-hIL-32 mice showed increased expression and secretion of TNFα, IL-1β, and IL-6 especially in response to
lipopolysaccharide stimulation. Moreover, serum TNFα concentration showed a clear increase in BM-hIL-32 mice. Cell-sorting
analysis of splenocytes showed that the expression of TNFα was increased in resting F4/80+ macrophages, and the expression of TNFα, IL-1β and IL-6 was increased in lipopolysaccharide-stimulated F4/80+ macrophages and CD11c+ dendritic cells. In fact, BM-hIL-32 mice showed exacerbation of collagen-antibody-induced arthritis and trinitrobenzen sulfonic
acid-induced colitis. In addition, the transfer of hIL-32β-producing CD4+ T cells significantly exacerbated collagen-induced arthritis, and a TNFα blockade cancelled the exacerbating effects of hIL-32β.
We therefore conclude that IL-32 is closely associated with TNFα, and contributes to the exacerbation of TNFα-related inflammatory
arthritis and colitis. 相似文献
3.
Kajiura-Kobayashi H Yoshida N Sagata N Yamashita M Nagahama Y 《Development genes and evolution》2000,210(8-9):416-425
Mos plays a crucial role in meiotic cell division in vertebrates. In Xenopus, Mos is involved in the initiation of oocyte maturation as an initiator and in the arrest at the metaphase II stage (MII)
as a component of the cytostatic factor (CSF). The function of Mos is mediated by MAP kinase (MAPK). We investigated the function
of the Mos/MAPK pathway during goldfish oocyte maturation induced by 17α,20β-dihydroxy-4-pregnen-3-one (17α,20β-DP), a natural
maturation-inducing hormone in fishes. Mos was absent in immature goldfish oocytes. It appeared before the onset of germinal
vesicle breakdown (GVBD), increased to a maximum in mature oocytes arrested at MII and disappeared after fertilization. MAPK
was activated after Mos synthesis but before maturation-promoting factor (MPF) activation, and its activity reached maximum
at MII. Injection of either Xenopus or goldfish c-mos mRNA into one blastomere of 2-cell-stage Xenopus and goldfish embryos induced metaphase arrest, suggesting that goldfish Mos has a CSF activity. Injection of constitutively
active Xenopus c-mos mRNA into immature goldfish oocytes induced MAPK activation, but neither MPF activation nor GVBD occurred. Conversely, the
injection of goldfish c-mos antisense RNA inhibited both Mos synthesis and MAPK activation in the 17α,20β-DP-treated oocytes, but these oocytes underwent
GVBD. These results indicate that the Mos/MAPK pathway is not essential for initiating goldfish oocyte maturation despite
its general function as a CSF. We discuss the general role of Mos/MAPK during oocyte maturation, with reference to the difference
in contents of inactive MPF (pre-MPF) stored in immature oocytes.
Received: 10 February 2000 / Accepted: 25 April 2000 相似文献
4.
In a previous report (Cebo et al. J Biol Chem 276 (2001) 5685–5691), it was established that biologically active recombinant human IL-1α and IL-1β had different carbohydrate-binding
properties. IL-1α recognized a di-antennary N-glycan with two α2-3-linked sialic acid residues, whereas IL-1β recognized the
GM4, a α2-3-linked sialylated glycosphingolipid. These different carbohydrate-binding properties of two interleukins binding
to the same receptor (IL-1R) could explain why these molecules had different biological effects and cell specificities. Molecular
modeling of the ligands and in silico docking experiments defined putative carbohydrate-recognition domains localized in the same area of the two molecules, a
domain different from that defined as the type I IL-1R binding domain. The calculated pattern of hydrogen bonding and of van
der Waals interactions fulfilled the essential features observed for calcium-independent lectins (mammalian, viral or bacterial).
The analysis of the same domain of the third members of this family of molecules, the IL-1R-antagonist, indicated it did not
fulfill the criteria for carbohydrate-recognition domains. It is proposed that its role as a pure antagonist is due to the
absence of lectin activity and consequently explained its inability to associate IL-1R with other surface molecular complexes
necessary for signaling. 相似文献
5.
Cartilaginous fish are the oldest extant jawed vertebrates and the oldest line to have placentae. Their pivotal evolutionary
position makes them attractive models to investigate the mechanisms involved in the maternal-fetal interaction. This study
describes the tissue expression of the cytokine interlukin-1 (IL-1) α, IL-1 β and its specific membrane receptor, IL-1 receptor
type I (IL-1R tI) in a placental cartilaginous fish, the smoothhound shark, Mustelus canis. The presence of this cytokine has been reported in many mammalian placentae, as well as in the placenta of a squamate reptile
and this study extends these observations to the cartilaginous fishes. The uteroplacental complex in M. canis consists of a yolk sac modified into a functional yolk sac placenta and complimentary uterine attachment sites. Immunohistochemistry
for IL-1 α, IL-1 β and the receptor reveals leucocytes of both the mother and fetus to be positive, as well as the apical
aspect of paraplacental cells and the apical vesicles in the umbilical cord epithelium. Yolk sac endoderm is also positive
with all the stains while the ectoderm is positive only for IL-1 α. Immunoreactivity in the uterine epithelium was obtained
for IL-1 α and the receptor. The egg envelope is always negative. 相似文献
6.
Farshad Malihi Azadeh Hosseini-Tabatabaei Hadi Esmaily Reza Khorasani Maryam Baeeri Mohammad Abdollahi 《Central European Journal of Biology》2009,4(3):369-380
Type 1 diabetes mellitus (T1DM) is characterized by an impairment of the insulin-secreting beta cells with an immunologic
base. Inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and free radicals are believed
to play key roles in destruction of pancreatic β cells. The present study was designed to investigate the effect of Silybum marianum seed extract (silymarin), a combination of several flavonolignans with immunomodulatory, anti-oxidant, and anti-inflammatory
potential on streptozotocin (STZ)-induced T1DM in mouse. Experimental T1DM was induced in male albino mice by IV injection
of multiplelow- doses of STZ for 5 days. Seventy-two male mice in separate groups received various doses of silymarin (20,
40, and 80 mg/kg) concomitant or after induction of diabetes for 21 days. Blood glucose and pancreatic biomarkers of inflammation
and toxic stress (IL-1β, TNF-α, myeloperoxidase, lipid peroxidation, protein oxidation, thiol molecules, and total antioxidant
capacity) were determined. Silymarin treatment reduced levels of inflammatory cytokines such as TNF-α and IL-1β and oxidative
stress mediators like myeloperoxidase activity, lipid peroxidation, carbonyl and thiol content of pancreatic tissue in an
almost dose dependent manner. No marked difference between the prevention of T1DM and the reversion of this disease by silymarin
was found. Use of silymarin seems to be helpful in T1DM when used as pretreatment or treatment. Benefit of silymarin in human
T1DM remains to be elucidated by clinical trials. 相似文献
7.
Balzer Sandrock Karen M. Hudson Douglas E. Williams Michael A. Lieberman 《In vitro cellular & developmental biology. Animal》1996,32(4):225-233
Summary The regulation of megakaryopoeisis by cytokines is not yet well understood. It is possible that autocrine loops are established
during megakaryocyte growth and differentiation, aiding in the maturation of these cells. The CHRF-288-11 human megakaryoblastic
cell line has been examined for cytokine production in growing cells and cells stimulated to differentiate by the addition
of phorbol esters. It has been demonstrated that these cells produce RNA corresponding to the interleukins IL-1α, 1β, 3, 7,
8, and 11, granulocyte-macrophage colony stimulating factor (GM-CSF), stem cell factor (SCF), transforming growth factor-β
(TGF-β), tumor necrosis factor-α (TNF-α), interferon-α (INF-α), and basic fibroblast growth factor (bFGF). Additionaly, RNA
corresponding to the receptors for IL-6, GM-CSF, SCF, INF-α,β, bFGF, and monocyte colony stimulating factor (M-CSF) were also
expressed by the cells. The receptor for TNF-α was detected immunologically. Analysis at the protein level demonstrated that
significant amounts of INF-α, TNF-α, GM-CSF, SCF, IL-1α, and a soluble form of the IL-6 receptor were produced by the cells.
Addition of phorbol esters to CHRF-288-11 cells enhances their megakaryocytic phenotype; such treatment also results in increased
secretion of INF-α, TNF-α, and GM-CSF. These results suggest that potential autocrine loops are established during the differentiation
of CHRF-288-11 cells, which may alter the capability of the cell to differentiate. These findings are similar to those recently
obtained for marrow-derived megakaryocytes (Jiang et al.) suggesting that CHRF-288-11 cells provide a useful model system
for the study of cytokine release during megakaryocyte differentiation. 相似文献
8.
In diabetes the endothelium is either chronically or transiently exposed to hyperglycemic conditions. In addition, endothelial
dysfunction in diabetes is related to changes in the inflammatory response and the turnover of extracellular matrix. This
study was undertaken to study the effects of inflammatory stimuli on one particular matrix component, the heparan sulfate
(HS) proteoglycans (PGs) synthesized by primary human umbilical cord vein endothelial cells (HUVEC). Such cells were cultured
in vitro in 5 mM and 25 mM glucose. The latter concentration was used to mimic hyperglycemic conditions in short-term experiments.
HUVEC were also cultured in the presence of the inflammatory agents tumor necrosis factor α (TNF-α), interleukin 1α (IL-1α),
interleukin 1β (IL-1β) and transforming growth factor β (TGF-β). The cells were labeled with 35S-sulfate and 35S-PGs were recovered for further analyses. The major part of the 35S-PGs was secreted to the medium, irrespective of type of stimuli. Secreted 35S-PGs were therefore isolated and subjected to further analyses. TNF-α and IL-1α slightly increased the release of 35S-PGs to the culture medium, whereas IL-1β treatment gave a significant increase. The different treatments neither changed
the ratio of 35S-HS and 35S-chondroitin sulfate (CS) nor the macromolecular properties of the 35S-PGs. However, the 35S-HS chains were slightly increased in size after TNF-α treatment, and slightly decreased after TGF-β treatment, but not affected
by the other treatments. Compositional analysis of labeled disaccharides showed changes in the amount of 6-O-sulfated glucosamine residues after treatment with TNF-α, IL-1α and IL-1β. Western immunoblotting showed that major HSPGs
recovered from these cells were collagen XVIII, perlecan and agrin, and that secretion of these distinct PGs was increased
after IL-1β stimulation. Hence, short term inflammatory stimuli increased the release of HSPGs in HUVEC and affected both
the size and sulfation pattern of HS, depending on type of stimuli. 相似文献
9.
Summary. The effect of taurine (Tau) and taurine chloramine (Tau-Cl) on the production of TNF-α, IL-1β, and IL-6 by peripheral blood mononuclear cells of healthy volunteers was examined. Cells were stimulated with bacterial
lipopolysaccharide (LPS) in the presence of either Tau or Tau-Cl. After 24 h culture the cytokine concentrations were measured
in both culture supernatants (secreted) and cell lysates (cell-associated) using ELISA. In LPS-stimulated cells Tau-Cl inhibited
both the secreted and cell-associated IL-1β and IL-6, while exerted dual effect on TNF-α production: raising it slightly at low and reducing at higher concentration. By contrast, Tau had no significant effect on
the cytokine production. These results indicate that Tau-Cl modulates synthesis of pro-inflammatory cytokines, and therefore
it may play a role in the initiation and propagation of immune response.
Received November 29, 2001 Accepted January 18, 2002 Published online August 30, 2002
Acknowledgments This research was supported by grants from the State Committee for Scientific Research of Poland (No 4 P05B 01018) and the
Institute of Rheumatology (No I/14). The Institute of Rheumatology is supported by a core grant from the State Committee for
Scientific Research of Poland.
Authors' address: Ewa Kontny, Ph.D., Department of Pathophysiology and Immunology, Institute of Rheumatology, Spartanska 1, 02-637 Warsaw,
Poland, E-mail: zpatiir@warman.com.pl
Abbreviations: Tau, taurine; Tau-Cl, taurine chloramine; LPS, lipopolysaccharide; TNF-α, tumor necrosis factor-α; IL-1β, interleukin 1β; IL-6, interleukin 6; PBMC, peripheral blood mononuclear cells 相似文献
10.
Mast cell (MC) activation in the rheumatoid lesion provides numerous mediators that contribute to inflammatory and degradative processes, especially at sites of cartilage erosion. MC activation in rheumatoid synovial tissue has often been associated with tumour necrosis factor (TNF)-α and interleukin (IL)-1β production by adjacent cell types. By contrast, our in situ and in vitro studies have shown that the production of IL-15 was independent of MC activation, and was not related to TNF-α and IL-1β expression. Primary cultures of dissociated rheumatoid synovial cells produced all three proinflammatory cytokines, with production of IL-1β exceeding that of TNF-α, which in turn exceeded that of IL-15. In vitro cultures of synovial macrophages, synovial fibroblasts and articular chondrocytes all produced detectable amounts of free IL-15, macrophages being the most effective. 相似文献
11.
Nath A Chattopadhya S Chattopadhyay U Sharma NK 《Cancer immunology, immunotherapy : CII》2006,55(12):1534-1541
The C–C chemokines, macrophage inflammatory protein (MIP)1α and MIP1β are potent chemoattractants for the monocytes, which form an important component of the stroma of tumor tissue and may regulate tumor growth and associated inflammation. We examined the role of MIP1α and MIP1β in inducing the release of inflammatory cytokines and the generation of tumoricidal monocytes from the peripheral blood monocytes (PBM) of healthy women and patients with carcinoma of breast (CaBr). Interleukin-1 (IL-1) and tumor necrosis factor (TNF) α release by the PBM was markedly stimulated by MIP1α in CaBr patients, but only marginally so in healthy women. In contrast, MIP1β stimulated the release of these cytokines by the PBM of healthy women, but failed to do so in CaBr patients. MIP1α, but not MIP1β, synergized with LPS in inducing the release of IL-1 from the PBM of both healthy women and CaBr patients. Both MIP1α and MIP1β augmented respiratory bursts in PBM and generated tumoricidal PBM that killed T24 cells, MIP1α being more effective in CaBr patients and MIP1β in healthy women. IFN-γ co-stimulated and IL-4 suppressed MIP1α and β-induced cytotoxicity in PBM. The synergy of IFN-γ was more marked with MIP1α than with MIP1β. The differential effects of MIP1α and MIP1β on the PBM of healthy women and CaBr patients co-related with the levels of expression of CCR1 and CCR5 in these monocytes. The expression of CCR5 was higher than that of CCR1 in the PBM of healthy women and the PBM of the CaBr patients showed overexpression of CCR1 and downregulation of CCR5. 相似文献
12.
Plasma essential trace elements, selenium, copper, zinc, and iron concentrations and the levels of immunoregulatory cytokines,
interleukin-1β (IL-1β), interleukin-2 receptor (IL-2r), IL-6, IL-8, and tumor necrosis factor-α (TNF-α) were evaluated in patients with cutaneous leishmaniasis (CL) to investigate a possible role of these cytokines on selenium,
zinc, copper, and iron homeostasis in CL patients. Plasma albumin levels were measured as an index of nutritional status.
Plasma selenium, zinc, and iron concentrations, and IL-2r levels were significantly lower, and copper concentrations and IL-1β, IL-8, IL-6 and TNF-α levels were significantly higher in patients with CL than those of healthy controls. There was no significant difference
in plasma albumin levels between two groups. There were positive important correlations between plasma selenium and IL-2r,
copper and IL-6, and copper and IL-1β, and negative correlations between selenium and IL-8, iron and TNF-α, and zinc and IL-1β contents in patients with CL. Our results showed that plasma trace element contents change in patients with CL. These changes
may not be a result of a specific deficiency from dietary inadequacies or imbalances, but, probably, a result of a part of
the defense strategies of an organism that is regulated by immunoregulatory cytokines. 相似文献
13.
Effects of representative members of the transforming growth factor-β (TGF-β) family, TGF-β1, activin A and BMP-2, on melanin
content and expression of pigment-producing enzymes were examined in B16 melanoma cells. Treatment with TGF-β1 or activin
A but not with BMP-2 significantly decreased melanin content and expression of Tyrosinase and Tyrp-1, suggesting an inhibitory effect of TGF-β1 and activin A on melanin synthesis. TGF-β1 completely inhibited melanin synthesis
induced by α-melanin stimulating hormone (α-MSH), whereas activin A only slightly did. As compared with parental B16 cells,
the inhibitory effects of TGF-β1 and activin A on melanin content were relative smaller in B16 F10 cells, a subline of B16
cells that contain more pigment. The present study indicates that in addition to TGF-β, activin negatively regulates melanogenesis
in the absence of α-MSH, but that the activity in the presence of α-MSH was slightly different between TGF-β and activin. 相似文献
14.
Li N Xu X Xiao B Zhu ED Li BS Liu Z Tang B Zou QM Liang HP Mao XH 《Molecular biology reports》2012,39(4):4655-4661
MicroRNAs have been implicated as a central regulator of the immune system. We have previously reported that Helicobacter pylori (H. pylori) was able to increase the expression of miR-146a, and miR-146a may negatively regulate H. pylori-induced inflammation, but the exact mechanism of how H. pylori contribute the induction of miR-146a is not clear. Here, we attempted to assess the role of H. pylori related proinflammatory cytokines including interleukin (IL)-8, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β, and
cytotoxin-associated gene A (CagA) virulence factor on the induction of miR-146a. We found that IL-8, TNF-α, and IL-1β could
contribute to the induction of miR-146a in gastric epithelial cell HGC-27 in NF-κB-dependent manner, while the induction of
miR-146a upon H. pylori stimulation was independent of above proinflammatory cytokines. Furthermore, overexpression of miR-146a reduced H. pylori—induced IL-8, TNF-α, and IL-1β. However, CagA had no effect on the miR-146a induction. Taken together, our study suggest that proinflammatory cytokines IL-8,
TNF-α, and IL-1β could contribute to the induction of miR-146a during H. pylori infection, while CagA is not necessarily required for miR-146a induction. miR-146a may function as novel negative regulators
to modulate the inflammation. 相似文献
15.
Masato Okamoto Ryoji Kaji Hisashi Goda Go Ohe Hideo Yoshida Mitsunobu Sato Hirofumi Kasatani 《Cancer immunology, immunotherapy : CII》1998,47(4):233-241
It has been reported that certain chemotherapeutic agents exhibit effects that enhance the antitumor host responses in the
patients with malignant diseases. In the present study, we investigated whether cis-diamminedichloroplatinum (cisplatin) and 5-fluorouracil (5-FU) may induce cytokines and effector cells with antitumor efficacy
in vivo and in vitro. The cultivation of human peripheral blood mononuclear cells (PBMC) in the presence of cisplatin (0–1.0
μg/ml) or 5-FU (0–5.0 μg/ml) resulted in the significant augmentation of natural killer (NK) and lymphokine-activated killer
(LAK) cell activities as well as generation of interferon (IFN) γ, tumor necrosis factor (TNF) α, β, interleukin(IL)-1β, IL-6
and IL-12 in vitro. In addition, all of these activities were almost completely neutralized by addition of anti-asialoGM1
antibody and complement (P < 0.05). In an in vivo model, the administration of anti-asialoGM1 antibody significantly shortened the survival time extended
by the treatment with cisplatin or 5-FU (P < 0.05), both on nude mice bearing salivary gland tumors and on syngeneic MethA-tumor-bearing BALB/c mice. Furthermore, high
levels of NK and LAK activities and significant increases of the numbers of cells positive for asialoGM1, IFNγ, TNFα, or IL-1β
were detected in the spleen cells derived from animals given cisplatin or 5-FU as compared with those given saline (P < 0.001–0.05). These findings clearly indicate that cisplatin and 5-FU are potent inducers of several types of cytokines and
effector cells carrying antitumor activity mediated by asialoGM1-positive cells (mainly NK cells) for the most part, and that
these abilities are closely associated with the in vivo antitumor effect of these agents.
Received: 23 July 1998 / Accepted: 10 September 1998 相似文献
16.
Transgenic mice containing a swine class I major histocompatibility complex (MHC) gene,PD1, express swine MHC (SLA) antigen. The tissue distribution of PD1 RNA parallels that observed in the swine, indicating that
the expression ofPD1 is regulated and thattrans-acting factors involved in this regulation have been conserved between the species. Although PD1 RNA levels were much greater
in transgenic spleen than in thymus, no difference in the chromatin organization of thePD1 gene was detected. In both tissues, a single DNase I hypersensitive site mapped within the 5′ flanking region. In vivo treatment
of the transgenics with mouse α, β-interferon increases PD1 expression in a number of tissues. In the spleen, this increase
parallels that observed for the endogenous transplantation antigen, Kb, but differs markedly from the differentiation antigen, Qa-2. Increases in cell surface expression of both PD1 and Kb occurred equally in splenic T- and B-cell populations following α,β-interferon treatment. In contrast, Qa-2 expression in
B cells was enhanced by α,β-interferon, whereas it was unaffected in T cells and thymocytes. 相似文献
17.
18.
Jean Roudier 《Arthritis research & therapy》2000,2(3):217-4
Most patients with rheumatoid arthritis (RA) express HLA-DR4, HLA-DR1 or HLA-DR10. These alleles share a common amino acid
motif in their third hypervariable regions: the shared epitope. In normals and patients with RA, HLA-DR genes exert a major
influence on the CD4 αβ T-cell repertoire, as shown by studies of AV and BV gene usage and by BV BJ gene usage by peripheral
blood CD4 αβ T-cells. However, the rheumatoid T-cell repertoire is not entirely under HLA-DR influence, as demonstrated by
discrepancies in VB JB gene usage between identical twins discordant for RA and by contraction of the CD4 αβ T-cell repertoire
in RA patients. Shared epitope positive HLA-DR alleles may shape the T-cell repertoire by presenting self peptides to CD4
T cells in the thymus. Peptides processed from HLA-DR molecules and encompassing the shared epitope may also be presented
by HLA-DQ and select CD4 αβ T cells in the thymus. Thus, shared epitope-positive alleles impose a frame on the T-cell repertoire.
This predisposing frame is further modified (by unknown factors) to obtain the contracted rheumatoid repertoire. 相似文献
19.
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
20.
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