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1.
Amim LH Pacheco AG Fonseca-Costa J Loredo CS Rabahi MF Melo MH Ribeiro FC Mello FC Oliveira MM Lapa e Silva JR Ottenhoff TH Kritski AL Santos AR 《Molecular biology reports》2008,35(4):563-566
Several genetic cytokine gene variants have been associated with host susceptibility to infectious diseases, including tuberculosis.
Based upon the importance of IFN-γ in protective immunity against Mycobacterium tuberculosis, and the functional role of the IFN-γ + 874T/A single nucleotide polymorphism in IFN-γ production, we genotyped 93 Brazilian
tuberculosis patients and 266 asymptomatic health care workers, including 150 individuals with a positive tuberculin skin
test, and analyzed the possible association of the +874A low IFN-γ producer allele with tuberculosis occurrence. Using multivariable
logistic regression models, genotype and allele frequencies of the mutant + 874A (low IFN-γ producer) allele were significantly
associated with tuberculosis disease. Heterozygous carriers had a 25% increased chance, while individuals presenting the A/A
homozygous genotype had an over two-fold risk of having active tuberculosis (95% CI, 1.16–5.91, P = 0.03). Despite the mixed ethnicity observed in Brazilian populations, the present data agree with observations reported
in other populations and thus demonstrate that the functional +874T/A IFN-γ gene polymorphism is associated with tuberculosis
in different populations. 相似文献
2.
Chintana Phawong Collins Ouma Piyatida Tangteerawatana Jarinee Thongshoob Tom Were Yuvadee Mahakunkijcharoen Duangrurdee Wattanasirichaigoon Douglas Jay Perkins Srisin Khusmith 《Immunogenetics》2010,62(6):345-356
Polymorphic variability in immune response genes, such as IL12B, encoding the IL-12p40 subunit is associated with susceptibility to severe malaria in African populations. Since the role
of genetic variation in conditioning severe malaria in Thai adults is largely unexplored, the functional association between
IL12B polymorphisms [i.e. IL12Bpro (rs17860508) and IL12B 3′ UTR T/G (rs3212227)], severe malaria and cytokine production was examined in patients with Plasmodium falciparum infections (n = 355) recruited from malaria endemic areas along the Thai–Myanmar border in northwest Thailand. Circulating IL-12p40 (p = 0.049) and IFN-γ (p = 0.051) were elevated in patients with severe malaria, while only IL-12p40 was significantly higher in severe malaria patients
with hyperparasitaemia (p = 0.046). Carriage of the IL12Bpro1.1 genotype was associated with enhanced severity of malaria (OR, 2.34; 95% CI, 0.94–5.81; p = 0.066) and hyperparasitaemia (OR, 3.42; 95% CI, 1.17–9.87; p = 0.025) relative to the IL12Bpro2.2 genotype (wild type). Individuals with the IL12Bpro1.1 genotype also had the lowest IL-12p40 (p = 0.002) and the highest IFN-γ (p = 0.004) levels. Construction of haplotypes revealed that carriage of the IL12Bpro-2/3′ UTR-T haplotype was associated with protection against severe malaria (OR, 0.51; 95% CI, 0.29–0.90; p = 0.020) and reduced circulating IFN-γ (p = 0.06). Thus, genotypic and haplotypic variation at IL12Bpro and IL12B 3′ UTR in this population influences susceptibility to severe malaria and functional changes in circulating IL-12p40 and
IFN-γ levels. Results presented here suggest that protection against severe malaria in Thai adults is associated with genotypic
variants that condition enhanced IL-12p40 and reduced IFN-γ levels. 相似文献
3.
Cheong JY Cho SW Chung SG Lee JA Yeo M Wang HJ Lee JE Hahm KB Kim JH 《Biochemical genetics》2006,44(5-6):246-255
The natural history of hepatitis B virus (HBV) infection is probably related to host immune factors. Interferon-γ (IFN-γ) plays significant roles in immune defense. This study was undertaken to investigate the association between HBV infection and single nucleotide polymorphisms (SNPs) of IFN-γ, IFN-γ receptor (IFNGR)-1 and 2, and interferon regulatory factor (IRF)-1 genes. Between March 2002 and December 2002, 614 Korean patients were enrolled in two different groups: an HBV clearance group (n = 201), who were hepatitis B surface antigen (HBsAg) negative with antibodies to HBsAg and hepatitis B core antigen, and an HBV persistence group (n = 413), who were repeatedly HBsAg positive. We assessed polymorphisms in the IFN-γ gene at position +874, in the IFNGR-1 gene at positions −56 and +95, in the IFNGR-2 gene at the second position of codon 64 (Gln64Arg), and in the IRF-1 gene promoter (−410, −388), and the genotype distributions of the HBV clearance and persistence groups were compared. On the basis of unconditional logistic regression analysis with adjustment for age and sex, no statistically significant association with susceptibility to persistent HBV infection was observed with the IFN-γ, IFNGR-1 and 2, and IRF-1 gene polymorphisms under the codominant, dominant, and recessive models. 相似文献
4.
5.
Wendy Ingram Shahram Kordasti Lucas Chan Linda D. Barber Gee J. Tye Nicola Hardwick Ghulam J. Mufti Farzin Farzaneh 《Cancer immunology, immunotherapy : CII》2009,58(10):1679-1690
Immunotherapeutic strategies are increasingly being explored as a method of enhancing anti-tumour immune responses in patients
with acute myeloid leukaemia (AML). Regulatory CD4+ T cells (Tregs) suppress effector T and natural killer (NK) cells and therefore pose a potential challenge to the efficacy
of immunotherapy. AML cells transduced with a lentivirus expressing CD80 (B7.1) and IL2 (LV-CD80/IL2) are capable of stimulating
T and NK cell cytotoxicity in vitro. This study examines the effect of CD80/IL2 modified AML cells on Treg number and function.
We report a significant increase in the number of CD8+ T cells (P = 0.046) CD3−CD56+ NK cells (P = 0.028) and CD3+CD4+CD25highFoxp3+ Tregs (P = 0.043) following stimulation for 7 days with allogeneic LV-CD80/IL2 AMLs. In contrast, autologous LV-CD80/IL2 AML cell
cultures provide a weaker stimulation with a lower number of CD8+ T cells (P = 0.011) and no change in NK cell or Treg numbers. However, an increase in cytotoxic CD8+ T cells and NK cells are detected following both allogeneic and autologous LV-CD80/IL2 stimulation as demonstrated by an
increase in IFN-γ and CD107a expression. Despite the presence of increased numbers of Tregs with suppressive activity in a
subset of cultures, increased lysis of unmodified AMLs was still achieved following allogeneic (day 0, 2.2%; day 7, 20.4%)
and more importantly, autologous LV-CD80/IL2 culture in which AML patients had recently received intensive chemotherapy (day
0, 0%; day 7, 16%). Vaccination with LV-CD80/IL2 therefore provides a potential strategy to enhance anti-leukaemia immune
responses without a concomitant stimulation of Treg-mediated inhibition of cytotoxic immunological responses. 相似文献
6.
Hilde Kelchtermans Evelien Schurgers Lies Geboes Tania Mitera Jo Van Damme Jacques Van Snick Catherine Uyttenhove Patrick Matthys 《Arthritis research & therapy》2009,11(4):R122-13
Introduction
Interleukin (IL)-17 is a pro-inflammatory cytokine in rheumatoid arthritis (RA) and collagen-induced arthritis (CIA). Since interferon (IFN)-γ inhibits Th17 cell development, IFN-γ receptor knockout (IFN-γR KO) mice develop CIA more readily. We took advantage of this model to analyse the mechanisms of action of IL-17 in arthritis. The role of IFN-γ on the effector mechanisms of IL-17 in an in vitro system was also investigated. 相似文献7.
8.
Cornforth AN Fowler AW Carbonell DJ Dillman RO 《Cancer immunology, immunotherapy : CII》2011,60(1):123-131
The use of whole cell tumor vaccines and various means of loading antigen onto dendritic cells have been under investigation
for over a decade. Induction of apoptosis and the exposure of immune-stimulating proteins are thought to be beneficial for
the use in immunotherapy protocols, but conclusive evidence in the clinical setting has been lacking. Incubation of melanoma
cell lines with interferon-gamma (IFN-γ) increased phosphatidylserine and calreticulin exposure, but not in the IFN-γ-resistant
cell line Lu-1205. Short-term autologous melanoma cell lines used for loading dendritic cells for immunotherapy showed differential
response to the pro-apoptotic effects of IFN-γ. These IFN-γ-treated tumor cells (TCs) were irradiated and used for loading
antigen for dendritic cell therapy. A log-rank comparison of survival for patients whose TCs were found to be either sensitive
(upregulated phosphatidylserine and calreticulin) or insensitive to IFN-γ revealed a strongly significant correlation to progression-free
(p = 0.003) and overall survival (p = 0.002) favorably in those patients whose cell lines were resistant to the proapoptotic effect of IFN-γ. These results suggest
that the use of IFN-γ in anti-melanoma dendritic cell-based immunotherapy may only be beneficial when the cells do not undergo
apoptosis in response to IFN-γ and support the contention that the use of some apoptotic cells in vaccines may be detrimental. 相似文献
9.
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
10.
Y. Li S. L. Yang Z. L. Tang W. T. Cui Y. L. Mu M. X. Chu S. H. Zhao Z. F. Wu K. M. Peng K. Li 《Molecular biology reports》2010,37(3):1309-1317
As a component of E3 ubiquitin protein ligases called SCFs, SKP2 protein belongs to a member of FBLs protein which is the biggest eukaryotic subfamily of F-BOX proteins with 12 members.
In this study, we cloned and sequenced partial cDNA, intron 1 and intron 6 of porcine SKP2 gene. The partial cDNA is 1,402 bp long and has an open reading frame of 1,272 bp which encodes 424 putative amino acids.
The deduced protein comprises a conserved F-BOX domain at position from the 90th to 140th amino acid. The phylogenetic tree
indicated that porcine SKP2 has the closest genetic relationship with bovine SKP2 than other selected animal species. Quantitative RT-PCR analysis displayed that the tissue expression level of porcine SKP2 fluctuated remarkably in a large range, and it expressed in thymus with the highest level and in longissimus dorsi muscle
with the lowest level. Two SNPs were identified, meanwhile, further polymorphism analysis with Cfr42I showed that AA genotype
was in dominance absolutely among four kinds of unrelated Chinese indigenous miniature and one introduced Landrace pig breeds.
In addition, association analysis with immune traits and blood parameters revealed that the SNP Cfr42I in intron 1 was significantly
associated with red cell distribution width of neonate piglets at 0 day (P = 0.027). 相似文献
11.
Y. Li S. L. Yang Z. L. Tang W. T. Cui Y. L. Mu M. X. Chu S. H. Zhao Z. F. Wu K. Li K. M. Peng 《Molecular biology reports》2010,37(1):579-585
As a kind of E3 ligase, the product of FBXL4 gene belongs to a member of FBLs which is the biggest eukaryotic subfamily of F-BOX proteins, it can recognize some substrate
through particular protein–protein interaction domains. To investigate its functions, the polymorphism and association analysis
was analyzed. The partial cDNA of porcine FBXL4 with 2384 bp long was first cloned; the deduced protein comprises a conserved F-BOX domain at position from the 277th to
332nd amino acid. The phylogenetic tree indicated porcine FBXL4 has the closest genetic relationship with bovine FBXL4 than other selected animal species. Ten tissue expression level of porcine FBXL4 mRNA fluctuated remarkably in a large range by quantitative RT-PCR analysis. For two identified SNPs, the genotyping analysis
of Tail showed TT genotype owned dominance in introduced Landrace pig and miniature Guizhou and Wuzhishan breeds, but CC genotype
was more than two other genotypes in miniature Laiwu breed. While in another genotyping analysis of BsaJI, CC genotype was
obviously more than other genotypes in two kinds of Chinese miniature pig breeds and introduced Landrace pig breeds. Furthermore,
the association analysis with immune traits and blood parameters revealed that SNP Tail was significantly associated with
the lymphocyte percentage (P = 0.0166) and the antibody levels for pseudorabies virus vaccination (P = 0.0001) of neonate piglets at 0 day. Meanwhile, SNP BsaJI was significantly associated with lymphocyte percentage of individuals
at 32 days (P = 0.0351), neutrophil percentage (P = 0.0005), the absolute lymphocyte count (P = 0.0458), and the mixed cells (P = 0.0010) of neonate piglets at 0 day. 相似文献
12.
Mukesh Kumar Xiaoyuan Kong Aruna K Behera Gary R Hellermann Richard F Lockey Shyam S Mohapatra 《Genetic vaccines and therapy》2003,1(1):3
Background
Allergic subjects produce relatively low amounts of IFN-γ, a pleiotropic Th-1 cytokine that downregulates Th2-associated airway inflammation and hyperresponsiveness (AHR), the hallmarks of allergic asthma. Adenovirus-mediated IFN-γ gene transfer reduces AHR, Th2 cytokine levels and lung inflammation in mice, but its use would be limited by the frequency of gene delivery required; therefore, we tested chitosan/IFN-γ pDNA nanoparticles (CIN) for in situ production of IFN-γ and its in vivo effects. 相似文献13.
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
14.
Association of the interferon-γ receptor variant (Val14Met) with systemic lupus erythematosus 总被引:4,自引:0,他引:4
Tanaka Y Nakashima H Hisano C Kohsaka T Nemoto Y Niiro H Otsuka T Otsuka T Imamura T Niho Y 《Immunogenetics》1999,49(4):266-271
Genetic factors seem to play a significant role in susceptibility to systemic lupus erythematosus (SLE). The purpose of this
study was to investigate whether the amino acid polymorphism (Val14Met) found within the IFN-γ receptor gene (IFNGR1) plays a prominent role in susceptibility to SLE. We found Val14Met located at the COOH terminal of the signal peptide of
the IFN-γ receptor. There was a significant difference in this polymorphism frequency between SLE patients and healthy populations.
To clarify whether this amino acid substitution resulted in the alteration of the receptor function, we evaluated the induction
of HLA-DR antigen expression on B cells by IFN-γ stimulation. There was also a significant difference in the induction of
HLA-DR by IFN-γ stimulation between B cells. Furthermore, an intracellular cytokine assay indicated that the Th1/Th2 balance
of Th cells bearing the variant receptor shifted to Th2. The genetic polymorphism found within the IFN-γ receptor gene (Val14Met)
may result in a shift to Th2, and this shift may increase susceptibility to SLE.
Received: 13 April 1998 / Revised: 30 July 1998 相似文献
15.
PA28 subunits of the mouse proteasome: primary structures and chromosomal localization of the genes 总被引:2,自引:0,他引:2
The 20S proteasome is a multi-subunit protease responsible for the production of peptides presented by major histocompatibility
complex (MHC) class I molecules. Recent evidence indicates that an interferon-γ (IFN-γ)-inducible PA28 activator complex enhances
the generation of class I binding peptides by altering the cleavage pattern of the proteasome. In the present study, we determined
the primary structures of the mouse PA28 α- and β-subunits. The deduced amino acid sequences of the α- and β-subunits were
49% identical. We also determined the primary structure of the mouse PA28 γ-subunit (Ki antigen), a protein of unknown function
structurally related to the α- and β-subunits. The amino acid sequence identity of the γ-subunit to the α- and β-subunits
was 40% and 32%, respectively. Interspecific backcross mapping showed that the mouse genes coding for the α- and β-subunits
(designated Psme1 and Psme2, respectively) are tightly linked and map close to the Atp5g1 locus on chromosome 14. Thus, unlike the LMP2 and LMP7 subunits, the IFN-γ-inducible subunits of PA28 are encoded outside
the MHC. The gene coding for the γ-subunit (designated Psme3) was mapped to the vicinity of the Brca1 locus on chromosome 11. A computer search of the DNA databases identified a γ-subunit-like protein in ticks and Caenorhabditis elegans, the organisms with no adaptive immune system. It appears that the IFN-γ-inducible α- and β-subunits emerged by gene duplication
from a γ-subunit-like precursor.
Received: 11 March 1997 相似文献
16.
17.
IFN-α regulates IL 10 production by CML cells in vitro 总被引:1,自引:0,他引:1
Graham Pawelec Elke Schlotz Arnika Rehbein 《Cancer immunology, immunotherapy : CII》1999,48(8):430-434
High levels of spontaneous in vitro IL 10 secretion by a subset of untreated chronic phase CML patients' cells are shown
to be decreased in the presence of IFN-α. However, the lower level of spontaneous IL 10 secretion by healthy control cells
are was not depressed by IFN-α. In contrast to its effects on IL 10 production, IFN-α increased the low spontaneous secretion
of IL 1α by patients' cells, bud did not further increase the higher levels of spontaneous IL 1β secretion by normal cells.
It had no effect on secretion of TNF-α by patients or normals. Spontaneous secretion of IL-1α (or IFN-γ) by patients' cells
was not observed whether or not IFN-α was present. Therefore, one mechanism of action of IFN-α in vivo may involve decreasing
endogenous IL 10 secretion (thereby reducing suppressive effects on T cell reactivity) and increasing IL 1β secretion (thereby
enhancing antigen presentation).
Received: November 1998 / Accepted: 1 March 1999 相似文献
18.
The full-length cDNA sequence of one porcine gene, ROPN1, was isolated using the rapid amplification of cDNA ends (RACE) method
based on one pig EST sequence which was highly homologous to the coding sequence of human ROPN1 gene. The porcine ROPN1 gene
encodes a protein of 212 amino acids which shares high homology with the rhophilin associated protein 1 (ROPN1) of eight species:
gray short-tailed opossum (96%), horse (95%), cattle (94%), mouse (93%), rat (92%), chimpanzee (85%), human (85%) and rhesus
monkey (85%). Phylogenetic analysis revealed that the porcine ROPN1 gene has a closer genetic relationship with the ROPN1
gene of gray short-tailed opossum. Polymorphism analysis showed that there was a T/C mutation at the position of 536 bp of
mRNA and this leaded to the amino acid alteration from the Arg residue to the Cys residue. PCR-Hae III-RFLP was established
to detect this T/C mutation and eight pig breeds display obvious genotype and allele frequency differences at this mutation
locus. Association of this SNP with litter size traits was assessed in Large White (n = 100) and Landrace (n = 100) pig populations, and results demonstrated that this polymorphic locus was significantly associated with the litter
size of first parity (P < 0.01) and all parities (P < 0.05) in Large White sows, and also significantly associated with the litter size of all parities in Landrace sows (P < 0.01). Therefore, ROPN1 gene could be a useful candidate gene in selection for increasing litter size in pigs. These data
serve as a foundation for further insight into this novel porcine gene. 相似文献
19.
20.
Mi YY Yu QQ Xu B Zhang LF Min ZC Hua LX Feng NH Yao Y 《Molecular biology reports》2011,38(7):4461-4467
Interferon gamma (IFN-γ) plays a pivotal role in antiproliferative, antitumor and antiviral activities. The +874 polymorphism
in IFN gene region reportedly affects cancer risk. However, pertinent studies offer conflicting results. To derive a more
precise estimation, we performed a meta-analysis based on 1,929 cases and 2,830 controls from 17 published case–control studies,
assessing the strength of the association using odds ratios with 95% confidence intervals. Our meta-analysis showed the evidence
that IFN-γ +874 T/A was not associated with increased cancer risk in ethnicity and source of controls. However, stratified
analysis by cancer type indicated a significantly increased risk of cervical cancer (AT vs. TT: OR = 1.10, 95% CI = 1.02–1.19,
P = 0.961 for heterogeneity). Further prospective researches with a larger single study are required to evaluate any association
with other types of cancer or in other populations. 相似文献