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1.
Inna G. Ovsyannikova Neelam Dhiman Iana H. Haralambieva Robert A. Vierkant Megan M. O’Byrne Robert M. Jacobson Gregory A. Poland 《Human genetics》2010,127(2):207-221
Toll-like, vitamin A and D receptors and other innate proteins participate in various immune functions. We determined whether
innate gene-sequence variations are associated with rubella vaccine-induced cytokine immune responses. We genotyped 714 healthy
children (11–19 years of age) after two doses of rubella-containing vaccine for 148 candidate SNP markers. Rubella virus-induced
cytokines were measured by ELISA. Twenty-two significant associations (range of P values 0.002–0.048) were found between SNPs in the vitamin A receptor family (RARA, RARB, TOP2B and RARG), vitamin D receptor
and downstream mediator of vitamin D signaling (RXRA) genes and rubella virus-specific (IFN-γ, IL-2, IL-10, TNF-α, and GM-CSF)
cytokine immune responses. A TLR3 gene promoter region SNP (rs5743305, −8441A > T) was associated with rubella-specific GM-CSF
secretion. Importantly, SNPs in the TRIM5 gene coding regions, rs3740996 (His43Tyr) and rs10838525 (Gln136Arg), were associated
with an allele dose-related secretion of rubella virus-specific TNF-α and IL-2/GM-CSF, respectively, and have been previously
shown to have functional consequences regarding the antiviral activity and susceptibility to HIV-1 infection. We identified
associations between individual SNPs and haplotypes in, or involving, the RIG-I (DDX58) gene and rubella-specific TNF-α secretion.
This is the first paper to present evidence that polymorphisms in the TLR, vitamin A, vitamin D receptor, and innate immunity
genes can influence adaptive cytokine responses to rubella vaccination. 相似文献
2.
Ovsyannikova IG Haralambieva IH Vierkant RA Pankratz VS Jacobson RM Poland GA 《Human genetics》2011,130(4):547-561
Toll-like receptors (TLRs) and their intracellular signaling molecules play an important role in innate immunity. In this study, we examined associations between polymorphisms in TLR family genes and measles vaccine-specific immune responses. We genotyped 764 subjects (11-22 years old) after two doses of measles vaccine for TLR signaling SNP markers (n = 454). The major alleles of coding SNPs in the TLR2 (rs3804100) and TLR4 (rs5030710) genes were associated with a dose-related increase (660 vs. 892 mIU/ml, p = 0.002) and a dose-related decrease (2,209 vs. 830 mIU/ml, p = 0.001) in measles-specific antibodies, respectively. A significant association was found between lower measles antibody levels and the haplotype ACGGCGAGAAAAGAGAAGAGAGAGAA (p = 0.01) in the MAP3K7 gene. Furthermore, the minor allele of a SNP (rs702966) of the KIAA1542 (IRF7) gene was associated with a dose-related decrease in IFN-γ Elispot responses (38 vs. 26 spot-forming cells per 2 × 10(5) PBMCs, p = 0.00002). We observed an additional 12 associations (p < 0.01) between coding (nonsynonymous and synonymous) polymorphisms within the TLRs (TLR2, 7, and 8), IKBKE, TICAM1, NFKBIA, IRAK2, and KIAA1542 genes and variations in measles-specific IL-2, IL-6, IFN-α, IFN-γ, IFNλ-1, and TNF-α secretion levels. Our data demonstrate that polymorphisms in TLR and other related immune response signaling molecules have significant effects on measles vaccine-associated immune responses. These data help to establish the genetic foundation for immune response variation in response to measles immunization and provide important insights for the rational development of new measles vaccines. 相似文献
3.
Daneshmandi S Pourfathollah AA Pourpak Z Heidarnazhad H Kalvanagh PA 《Molecular biology reports》2012,39(2):1845-1853
Asthma is a multifactor inflammatory disorder, and its management requires understanding of its various pathogenesis and control
mechanisms. Cytokines and other inflammatory mediators are important factors in asthma pathophysiology. In this study, we
evaluated the role of cytokine polymorphisms in the asthma susceptibility, progress, control, and lung functions. IL-4-C590T
polymorphism by PCR-RFLP method, IFN-γ T+874A, TNF-α-A308G, IL-6 G−174C and TGF-β T+869C variants by ARMS-PCR method and IgE
serum level by ELISA technique were determined in 81 asthmatic patients and 124 normal subjects. Asthma diagnosis, treatment
and control levels were considered using standard schemes and criteria. TNF-α−308GA genotype was more frequent in asthmatics
(P = 0.025, OR 3.352), and polymorphisms between different asthma control levels (P > 0.05) were not different. IFN-γ+874AT genotype had a positive correlation with the familial history of asthma (P = 0.034, OR 2.688). IL-6−174C allele (P = 0.045), TNF-α−308GG genotype (P = 0.002) and TNF-α−308G allele (P = 0.004) showed reduced values, and TNF-α−308GA genotype (P = 0.002) increased FEF25-75 value in asthmatics. IFN-γ+874AA genotype caused a decrease in FVC factor (P = 0.045). This study showed that TNF-α−308GA is a risk factor for asthma, but cytokine gene variants do not affect asthma
control and IgE serum levels. Variants producing lower levels of IL-6, TNF-α and IFN-γ are associated with reduced pulmonary
capacities. To achieve an appropriate schema for asthma management, further studies with consideration of different aspects
in a larger group of patients would be more elucidative. 相似文献
4.
Choi IY Moon PD Koo HN Myung NY Kim SJ Lee JH Han SH Moon G Seo SY Sung HJ Park RK Jeong HJ Um JY Kim HM Hong SH 《In vitro cellular & developmental biology. Animal》2007,43(7):215-221
To explore effects of Forsythia koreana methanol extract (FKME) on mast cell-mediated allergic and inflammatory properties, the effect of FKME was evaluated on compound
48/80-induced systemic anaphylaxis, ear swelling, and anti-dinitrophenyl (DNP) immunoglobulin E (IgE)-induced passive cutaneous
anaphylaxis (PCA). In addition, the effect of FKME was investigated on the histamine release from rat peritoneal mast cells
(RPMCs) stimulated by compound 48/80, which promotes histamine release. The human mast cell line HMC-1 was stimulated by phorbol
12-myristate 13-acetate plus calcium ionophore A23187. Activated HMC-1 can produce several proinflammatory and chemotactic
cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-8. Cytokine levels in the culture supernatant
were measured by an enzyme-linked immunosorbent assay. Cytotoxicity by FKME was determined by a 3-(4,5-dimethylthiazol-2-yl)-diphenyl-tetrazolium
bromide (MTT) assay. FKME inhibited compound 48/80-induced systemic anaphylactic shock and ear swelling in mice. When 1 g/kg
FKME was pretreated or posttreated with mice, compound 48/80-induced mice morality was 50 and 66.7%, respectively. One gram
per kilogram of FKME pretreatment inhibited ear-swelling responses derived from compound 48/80 by 29.75%. A PCA reaction was
inhibited by 17.9%. In an in vitro model, FKME (1 mg/ml) inhibited histamine release from the RPMCs by 13.8% and TNF-α, IL-6,
and IL-8 production from HMC-1 cells by 71.16% (P < 0.001), 86.72% (P < 0.001), and 44.6%, respectively. However, FKME had no cytotoxic effects on cell viability. In conclusion, FKME inhibited
not only systemic anaphylaxis and ear swelling induced by compound 48/80 but also inhibited a PCA reaction induced by anti-DNP
IgE in vivo. Treatment with FKME showed significant inhibitory effects on histamine, TNF-α, IL-6, and IL-8 release from mast
cells. 相似文献
5.
The aim of this study was to explore whether the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) or tumor necrosis factor-α
(TNF-α) polymorphisms contribute to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) susceptibility.
The authors conducted a meta-analysis on associations between polymorphisms of the 3′ untranslated region (UTR) microsatellite
at exon 3, exon 4 CT60 (A/G), exon 1 +49 (A/G), and promoter -318 (C/T) of CTLA-4, and TNF-α promoter-308 (A/G) and AAV susceptibility
as determined using; (1) allelic contrast and (2) homozygote contrast, (3) recessive, and (4) dominant models. A total of
11 comparisons were considered in this meta-analysis. These studies encompassed 7 CTLA-4 studies and 4 TNF-α studies in 10
European populations and 1 Asian population. The (AT)n repeat polymorphisms of CTLA-4 were found to be significantly associated with AAV in European populations (OR of 86 vs. xx
allele = 0.402, 95% CI = 0.184–0.875, P = 0.022). The one study conducted on this polymorphism in Asians showed no significant association with AAV. Meta-analysis
of the 86/86 (recessive effect), 86/86 and 86/xx (dominant effect), and 86/86 vs. xx/xx (homozygote contrast) of the (AT)n repeat revealed a significant association with AAV in Europeans. Both the CTLA-4 CT60 and +49 polymorphisms were found to be significantly associated with AAV in European populations, and allele and genotype-based
analyses showed a significant association between the CTLA-4 CT60 and +49 polymorphisms with AAV in Europeans (OR of the A allele of CT60 = 0.769, 95% CI = 0.619–0.017, P = 0.035; OR of the T allele of +49 = 1.382, 95% CI = 1.147–1.664, P = 0.001, respectively). Meta-analysis of the CTLA-4 -318 polymorphism failed to identify any association with AAV. Furthermore, meta-analysis of the AA genotype, the AA and
AG genotypes, and the A allele of TNF-α failed to reveal any association with Wegener’s granulomatosis (WG). This meta-analysis
demonstrates that the CTLA-4 polymorphisms confer susceptibility to AAV in Europeans. In contrast, no association was found
between the TNF-α-308 polymorphism and susceptibility to WG in Europeans. 相似文献
6.
7.
Zheng Jun Li Kyung-Cheol Sohn Dae-Kyoung Choi Ge Shi Dongkyun Hong Han-Eul Lee Kyu Uang Whang Young Ho Lee Myung Im Young Lee Young-Joon Seo Chang Deok Kim Jeung-Hoon Lee 《PloS one》2013,8(10)
Imiquimod is known to exert its effects through Toll-like receptor 7 (TLR7) and/or TLR8, resulting in expression of proinflammatory cytokines and chemokines. Keratinocytes have not been reported to constitutively express TLR7 and TLR8, and the action of imiquimod is thought to be mediated by the adenine receptor, not TLR7 or TLR8. In this study, we revealed the expression of TLR7 in keratinocytes after calcium-induced differentiation. After addition of calcium to cultured keratinocytes, the immunological responses induced by imiquimod, such as activation of NF-κB and induction of TNF-α and IL-8, were more rapid and stronger. In addition, imiquimod induced the expression TLR7, and acted synergistically with calcium to induce proinflammatory cytokines. We confirmed that the responses induced by imiquimod were significantly inhibited by microRNAs suppressing TLR7 expression. These results suggest that TLR7 expressed in keratinocytes play key roles in the activation of NF-κB signaling by imiquimod, and that their modulation in keratinocytes could provide therapeutic potential for many inflammatory skin diseases. 相似文献
8.
The expression of monocyte cell-surface receptors represents one index of immune dysfunction, which is common with aging.
Although mouse models of aging are prevalent, monocyte subset assessment is rare. Our purpose was to compare cell receptor
expression on classic (CD115+/Gr-1high) and non-classic (CD115+/Gr-1low) monocytes from 80- or 20-week-old CD-1 mice. Three-colour flow cytometry was used to determine the concentration of monocyte
subsets and their respective cell-surface expression of TLR2, TLR4, CD80, CD86, MHC II and CD54. These receptors were selected
because they have been previously associated with altered monocyte function. Data were analysed with independent t-tests; significance was set at P < 0.05. Old mice had a greater concentration of both classic (258%, P = 0.003) and non-classic (70%, P = 0.026) monocytes. The classic : non-classic monocyte ratio doubled in old as compared with that in young mice (P = 0.006), indicating a pro-inflammatory shift. TLR4 (↓27%, P = 0.001) and CD80 (↓37%, P = 0.004) were decreased on classic monocytes from old as compared with those from young mice. TLR2 (↑24%, P = 0.002) and MHCII (↓21%, P = 0.026) were altered on non-classic monocytes from old as compared with those from young mice. The increased classic : non-classic
monocyte ratio combined with changes in the cell-surface receptor expression on both monocyte subsets is indicative of immune
dysfunction, which may increase age-associated disease risk. 相似文献
9.
Kerstin Müller Rainer Altenkamp Jens Raila Daniel Schmidt Robert Dietrich Andrea Hurtienne Michael Wink Oliver Krone Leo Brunnberg Florian J. Schweigert 《European Journal of Wildlife Research》2011,57(5):1043-1049
In this study, we investigated the α-tocopherol plasma concentrations in healthy free-ranging nestlings of the white-tailed
sea eagle (Haliaeetus albicilla) (n = 32), osprey (Pandion haliaetus) (n = 39), northern goshawk (Accipiter gentilis) (n = 25), common buzzard (Buteo buteo) (n = 31), and honey buzzard (Pernis apivorus) (n = 18) as well as of free-ranging adults of the white-tailed sea eagle (n = 10), osprey (n = 31), and northern goshawk (n = 45). α-Tocopherol plasma concentrations were determined by reverse-phase high-performance liquid chromatography. α-Tocopherol
plasma concentrations in nestlings of osprey, white-tailed sea eagle, and northern goshawk did not differ significantly amongst
the species, but the common buzzard and honey buzzard nestlings had significantly lower α-tocopherol plasma concentrations
than nestlings of the other species (both P < 0.001). Adult male ospreys and white-tailed sea eagles had significantly higher α-tocopherol concentrations compared to
adult females (both P < 0.005). Adult ospreys and northern goshawks had significantly higher α-tocopherol plasma concentrations compared to their
nestlings (both P < 0.001). In adult female northern goshawks, plasma concentrations of α-tocopherol increased significantly before egg laying
(P < 0.001). These results demonstrate α-tocopherol plasma concentrations in birds of prey to be species specific and influenced
by age and reproductive status. 相似文献
10.
Watanabe A Shimokawa T Moriyama M Komine F Amaki S Arakawa Y Ra C 《Immunogenetics》2006,58(12):937-946
Fc receptor for IgA (FcαR, CD89) is capable of triggering IgA-mediated immune responses to pathogens and has been proposed to function in circulating IgA clearance. Because inheritable variations modifying individual immune responses or immunoglobulin catabolism may affect the chronicity of viral infection, we investigated whether promoter polymorphisms of the FcαR gene (FCAR) affect chronic hepatitis C virus (HCV) infection and its disease progression. The two −311T/C and −142T/C single-nucleotide polymorphisms (SNPs) were studied by direct DNA sequencing in 177 Japanese patients with chronic hepatitis C (CHC). Both −311CC and −142CC genotypes were more frequent in CHC patients (15.9 and 18.6%) compared with 210 healthy controls (5.7 and 10.0%) [p = 0.001, odds ratio (OR) = 3.10, 95% confidence interval CI) = 1.53–6.30 and p = 0.014, OR = 2.06, 95% CI = 1.14–3.72, respectively], and were associated with infection with HCV genotype 2a/2b (p = 0.019 and p = 0.005, respectively). Conversely, −311CC and −142CC were decreased in 59 patients at advanced stages of disease as assessed on the basis of hepatic fibrosis markers such as decreased platelet count (PLT) ( < 150,000/μl) (5.1 and 8.5%) compared with 91 patients with normal PLT ( ≥ 150,000/μl) (24.2 and 26.4%) (p = 0.006 and p = 0.005, respectively). Moreover, among the patients with normal PLT (but not with decreased PLT), −311CC or −142CC was significantly associated with decreased serum IgA levels (p = 0.023 or p = 0.007, respectively). These results suggest that the FCAR promoter SNPs may be related to chronic HCV infection and disease progression in Japanese CHC, which might be explained by altered FcαR expression affecting IgA-mediated immune responses and/or IgA catabolism. 相似文献
11.
Behaviour of interleukin-2 serum levels in advanced non-small-cell lung cancer patients: relationship with response to therapy and survival 总被引:8,自引:0,他引:8
Orditura M Romano C De Vita F Galizia G Lieto E Infusino S De Cataldis G Catalano G 《Cancer immunology, immunotherapy : CII》2000,49(10):530-536
Interleukin(IL)-2 is a T helper (Th) 1 type cytokine that has been shown to play an important role in antitumour immune responses.
In this study, the prognostic significance of serum IL-2 levels was investigated in 60 advanced non-small-cell lung cancer
(NSCLC) patients. IL-2 serum levels were determined before chemotherapy, at the end of chemotherapy and during follow-up,
using a commercially available enzyme-linked immunoadsorbent assay kit. The results were analysed according to the response
to therapy and were used to generate a model predicting overall survival and time to treatment failure. All 60 patients were
shown to have higher IL-2 serum levels than controls (P < 0.0001). Stage IV patients had significantly lower IL-2 levels than stage III patients (P < 0.0001), although they were still significantly higher than controls (P < 0.0001). It is interesting that, when patients were divided into responders and non-responders according to the response
to therapy, the former were shown to have significantly higher pre-chemotherapy levels than the latter (P < 0.0001). Moreover, a further significant increase in IL-2 serum levels (P=0.004) and a significant decrease (P < 0.0001) were shown in responders and non-responders, respectively at the end of the therapy. Using univariate and multivariate
analyses, both overall survival and time to treatment failure were shown to be affected by the mean pathological levels of
IL-2. Furthermore, the prognostic significance of the serum level of IL-2 was confirmed by the stepwise regression analysis.
In conclusion, determination of pre-treatment IL-2 serum levels was shown to be of independent prognostic utility in patients
with advanced NSCLC; therefore, its possible use for prediction of outcome is proposed.
Received: 16 March 2000 / Accepted: 27 July 2000 相似文献
12.
Toll-like receptor 4 (TLR4) is a receptor protein that binds pathogen ligands, which are mainly associated with Gram-negative
bacteria. The objective of this study was to investigate the association of nucleotide polymorphisms in TLR4 with infectious
bovine keratoconjunctivitis (IBK), or pinkeye, incidence in American Angus cattle. Animals with previously calculated breeding
values for IBK susceptibility were used to identify two SNPs in TLR4; Int1 (A/G) in intron1 (−26 Ex2 position) and Ex3 (C/T)
in exon3 (1,678 position). To investigate the possible role of these SNPs in IBK susceptibility, the disease incidence information
was collected on 370 calves raised in Iowa at two time points—June or August (disease season) and October (at weaning) and
genotyped using PCR-RFLP protocols. In statistical models including year, pasture management group, and SNP, the Int1 SNP
had a significant effect on IBK infection rates both in-season (P < 0.05) and at weaning (P < 0.01), whereas the Ex3 SNP was not significant (P > 0.79) at either time point. Furthermore, the Int1 SNP alone could account for 2.1% of phenotypic variation in IBK infection
during the disease season and 3.0% of phenotypic variation in IBK infection at the time of weaning. These data indicate that
there is a relationship between Int1 genotype and the rate of IBK infection in American Angus cattle. 相似文献
13.
Atle Wibe Anna-Karin Borg-Karlson Torbjörn Norin Hanna Mustaparta 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1997,180(6):585-595
Naturally produced plant volatiles, eliciting responses of single olfactory receptor neurons in the pine weevil, have been
identified by gas chromatography linked with mass spectrometry. The receptor neurons (n = 72) were classified in 30 types, according to the compound which elicited the strongest response in each neuron, 20 of
which compounds were identified. Most potent for 14 types of neurons (n = 50) were monoterpenes, including bicyclic (e.g. α-pinene, camphor and myrtenal) for 8 types (n = 32), monocyclic (limonene, carvone, α-terpinene) for 3 types (n = 12) and acyclic (e.g. β-myrcene and linalool) for 3 types (n = 6). Other compounds eliciting strongest responses of a neuron were five sesquiterpenes, including α-copaene and a farnesene-isomer,
and an anethole type which has no biosynthetic relationship with terpenes. Within one type, receptor neurons with quite selective
responses to the most potent compound as well as neurons with additional responses to several, structurally similar compounds
were found, indicating that the neurons may have the same functional types of membrane receptors, but different sensitivities.
Response spectra of neurons within the bicyclic-, mono-cyclic and acyclic types showed more overlapping than across the neuron
types. Minimal overlapping response spectra was found between monoterpene and sesquiterpene neurons. The results suggest that
this structure-activity relationship is significant for encoding plant odour information in the pipe weevil.
Accepted: 6 January 1997 相似文献
14.
Yi-Chun Chen Fen-Ju Hu Phoebe Chen Yih-Ru Wu Hsiu-Chuan Wu Sien-Tsong Chen Guey-Jen Lee-Chen Chiung-Mei Chen 《BMC neurology》2010,10(1):41
Background
Genetic factors may play a role in susceptibility to spontaneous deep intracerebral hemorrhage (SDICH). Previous studies have shown that TNF-α gene variation was associated with risks of subarachnoid hemorrhage in multiple ethnicities. The present case-control study tested the hypothesis that genetic variations of the TNF-α gene may affect the risk of Taiwanese SDICH. We examined the association of SDICH risks with four single nucleotide polymorphisms (SNPs) within the TNF-α gene promoter, namely T-1031C, C-863A, C-857T, and G-308A. 相似文献15.
16.
Mohamed A. Haidara Mohamed D. Morsy Hesham A. Abdel-Razek Dimitri P. Mikhailidis Esma R. Isenovic 《Journal of physiology and biochemistry》2010,66(3):255-264
Septicemia leads to oxidative stress with overproduction of reactive-oxygen species (ROS) and consumption of endogenous antioxidant
enzymes. We tested a twofold hypothesis: (1) does oxidative stress (OxS) induced by sepsis acting alone or in concert with
augmented inflammatory processes contributes to sepsis-related vascular dysfunction, and, (2) whether ozone (O3) and l-canavanine (CAV) mitigate the negative impact of the aforementioned phenomena. We investigated the relative impact of treatment
with CAV and/or O3 on vascular OxS associated vascular functional changes in septicemic rats. For this study, 60 male Sprague–Dawley rats were
used and divided into six experimental groups (n = 10): control group (C), sham-operated (Sham), septicemic rats (S), S rats treated with CAV (100 mg/kg. i.p; S + CAV), S
rats treated with O3 (1.2 mg/kg, i.p.; S + O3) and S rats treated with both O3 and CAV (S + O3 + CAV). After 22 h, the mean arterial blood pressure (MAP), the aortic ring vascular reactivity to phenylephrine, abdominal
aortic blood flow (AABF), serum tumor necrosis factor-α (TNF-α) and plasma nitrite/nitrate (NOx) concentration were measured.
In addition, hepatic antioxidant enzyme activities sodium dismutase (SOD) and glutathione peroxidase (GSH-Px) were estimated.
Septicemia caused significant elevation of serum TNF-α (p < 0.001) and plasma NOx (p < 0.001) and significant (p < 0.001) reduction of AABF (p < 0.001), aortic vascular response to phenylephrine (p < 0.001), MAP (p < 0.001) and hepatic SOD and GSH-Px activity (p < 0.001) compared with the C group, while treatment with O3 and/or CAV induced significant amelioration of all those increases. Abnormalities were attenuated to a similar extent with
treatment with both O3 and CAV. These results suggested that concomitant administration of O3 and CAV alleviated the compromised vascular reactivity in septicemic conditions and prevent its progression into septic shock
compared with each alone. 相似文献
17.
Tumor necrosis factor-alpha (TNF-α) has been regarded as a candidate gene for Crohn’s disease (CD) based on its inflammatory function in immune reaction and
the clinical effectiveness of anti-TNF-α therapy. However, studies to date have reported inconsistent findings for the association
between TNF-α and CD. The PubMed, EMBASE, and Medline databases were systematically reviewed from all English language publications
up to April, 2011. A total of twenty-nine studies concerning the association between CD and the TNF-α promoter polymorphisms of −308G/A, −857C/T and −238G/A were identified, among of them only twenty-three studies match the
inclusion criteria (including 3,843 cases and 6,260 controls) and were selected for the statistical test. We found that neither
the G allele of −308G/A (OR 1.02, 95% CI 0.87–1.19, P = 0.84), C allele of −857C/T (OR 0.97, 95% CI 0.86–1.09, P = 0.57) and G allele of −238G/A (OR 0.91, 95% CI 0.70–1.18, P = 0.48), and nor their GG (OR 1.05, 95% CI 0.88–1.25, P = 0.59), CC (OR 0.98, 95% CI 0.86–1.12, P = 0.76) and GG (OR 0.92, 95% CI 0.70–1.21, P = 0.55) genotypes were associated with CD susceptibility, respectively. Our meta-analysis demonstrates that three promoter
polymorphisms of TNF-α above may not confer susceptibility to CD. 相似文献
18.
Immunologic significance of HLA class I genes in measles virus-specific IFN-γ and IL-4 cytokine immune responses 总被引:2,自引:0,他引:2
Ovsyannikova IG Ryan JE Vierkant RA Pankratz VS Jacobson RM Poland GA 《Immunogenetics》2005,57(11):828-836
The variability of immune responses modulated by human leukocyte antigen (HLA) genes and secreted cytokines is a significant
factor in the development of a protective effect of measles vaccine. We studied the association between type 1 helper T cells
(Th1)- and Th2-like cytokine immune responses and HLA class I alleles among 339 schoolchildren who previously received two
doses of the measles vaccine. Median values for measles-specific interferon gamma (IFN-γ) and interleukin-4 (IL-4) cytokines
were 40.7 pg/ml [interquartile range (IQR) 8.1–176.7] and 9.7 pg/ml (IQR 2.8–24.3), respectively. Class I HLA-A (*0101 and
*3101) and HLA-Cw (*0303 and *0501) alleles were significantly associated with measles-virus-induced IFN-γ secretion. HLA-A*3101
and Cw*0303 were associated with a higher median IFN-γ response, while A*0101 and Cw*0501 were associated with lower measles-specific
IFN-γ response. We found limited associations between HLA class I gene polymorphisms and Th2-like (IL-4) immune responses
after measles vaccination, indicating that HLA class I molecules may have a limited effect on measles-vaccine-induced IL-4
secretion. Understanding the genetic factors that influence variations in cytokine secretion following measles vaccination
will provide insight into the factors that influence both cell-mediated and humoral immunity to measles. 相似文献
19.
Cadmium (Cd) exposure has been recognized to result in a wide variety of cellular responses, including oxidative stress and
body weight loss. The aim of the present study was to examine the effect of lycopene supplementation on the antioxidant defense
system, lipid peroxidation (LPO) level, nitric oxide (NO), tumor necrosis factor alpha (TNF-α) production, and body weight
in Cd-exposed rats. Animals were divided into four groups (n = 7): control, Cd-treated, Cd plus lycopene-treated, and lycopene-treated. Cadmium (as CdCl2) was administrated orally for 20 days (6.6 mg kg−1 day−1), and lycopene (10 mg kg−1 day−1) was similarly administered. Lycopene administration significantly suppressed Cd-induced LPO in plasma and kidney homogenates.
Lycopene also reversed Cd-decreased body weight compared to the control. Cadmium treatment had diverse effects on the antioxidant
enzyme activities. Although antioxidant superoxide dismutase activity was unchanged, glutathione peroxidase activity was decreased,
and catalase activity was elevated in kidney homogenates of Cd-administrated group. However, lycopene treatment reversed Cd-changed
enzyme activities to the control level. Xanthine oxidase activity and TNF-α concentration were not altered by Cd administration,
indicating that superoxide anion production and inflammation were not stimulated. Cadmium did not change NO levels in kidney
homogenates but decreased those in plasma, and this effect was not prevented by lycopene supplementation. The result suggests
that consumption of adequate levels of lycopene may be useful to prevent heavy-metal-induced LPO and body weight loss. 相似文献
20.
Woehrle T Du W Goetz A Hsu HY Joos TO Weiss M Bauer U Brueckner UB Marion Schneider E 《Cytokine》2008,41(3):322-329
Toll-like receptors (TLRs) are crucial pattern-recognition receptors (PRRs) for activation of innate and adapted immunity. TLR2 heterodimerizes with TLR1 or TLR6 to recognize multiple pathogen-associated molecular patterns (PAMPs) of fungi, Gram-positive pathogens, and mycobacteria. Receptor activation culminates in monocyte, T-helper (Th)1, and Th2 cytokine release. Single nucleotide polymorphisms (SNPs) Arg753Gln and Arg677Trp affect TLR2 responsiveness and may contribute to the course of sepsis, which is associated with substantial morbidity and mortality during intensive care treatment. We genotyped 325 critically ill patients with septic shock, and performed a detailed clinical follow-up with 47 of these patients. Here, we investigated whether distinct sepsis episodes result in defined plasma cytokine patterns, and whether cytokine profiles may be linked to the TLR2 polymorphisms. Blood sampling was done daily and microbiological testing was performed on a routine basis. DNA was extracted from whole blood and TLR2 SNPs were typed by pyrosequencing. Cytokines were measured by multiplexed array technologies and the leukocyte phenotype was determined by flow cytometry. Among the 325 ICU patients, 17 individuals (5.2%) were heterozygous for Arg753Gln. The SNP Arg677Trp was not found in any patient. Episodes of Gram-negative, Gram-positive, and Candida sepsis were recorded. During Gram-positive sepsis, the cytokine pattern did not differ between Arg753Gln heterozygous patients and wild type patients. By contrast, during Candida sepsis, the Arg753Gln heterozygous patients showed biomarker patterns that differed from wild type patients with elevated TNF-α plasma concentrations, but reduced IFN-γ and IL-8 levels. In conclusion, TLR2 SNP Arg753Gln results in altered cytokine release in response to Candida but not to Gram-positive sepsis. 相似文献