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Objective To investigate the association between promoter polymorphisms of interferon-alpha receptor-1 (IFNAR1) gene and the treatment response to interferon-alpha (IFN-α) in patients with chronic hepatitis B (CHB). Methods Sixty-one CHB patients who consented to receive IFN-a therapy were enrolled in this study. The subjects were treated with recombinant IFN-α2b 500 MU intramuscular injection qod for 48 weeks. The treatment responses were monitored.Meanwhile, the promoters of IFNAR1 gene in these patients were sequenced. Measurement data were analyzed by t test and enumeration data were analyzed by Chi square test. Results Twenty-two treated patients achieved complete response. Eight patients achieved partial response and 31 had no response. Polymorphisms were identified in the promoter of IFNAR1 gene, which included C/T substitution at locus -408, C/T substitution at locus-3 and GT microsatellite repeat sequence at locus-77 [-77(GT)n]. The three polymorphisms were in linkage and composed some haplotypes,such as - 408C/-77(GT)5/-3C. The response rate to IFN-α in CHB patients with genotypes -408C/-77(GT)5/-3C, -408C/-77(GT)5/-3C, and-408C/-77(GT)5/-3C, non -408C/ - 77(GT)5/-3C in IFNAR1 gene promoter was higher than that in patients with genotype non -408C/-77(GT)5/-3C, non-408C/- 77(GT)5/- 3C (61. 0% vs 25. 0%, x2=6. 961, P =0.008). Conclusions CHB patients with genotype-408C/ - 77(GT)5/ - 3C, -408C/-77(GT)5/-3C and -408C/ -77(GT)5/ -3C, non -408C/ -77(GT)5/-3C in the promoter of the IFNAR1 gene are prone to have better response to IFN-a treatment. Polymorphisms in the promoter of IFN-αgene are associated with the treatment response to IFN-α in CHB patients.
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Objective To investigate the effects of triptolide on the expression of a series of proteins associated with interferon-γ (IFN-γ)signaling in HaCaT keratinocytes.Methods After pretreatment with difrerent dosages of triptolide(10-10-10-7 mol/L),HaCaT cells were stimulated by recombinant human IFN-γ(rhIFN-γ,500 U/mL)for various periods followed by the collection of cells.Then,total protein was extracted from these cells and subjected to Western blotting for the detection of expression of interferon-γ receptor α(IFN-γRα),phosphorylated Janus kinase 2(pJAK2)and suppressor of cytokine signaling (SOCS1).Results Triptolide at the concentrations of 10-8 mol/L and 10-7 mol/L significantly inhibited the IFN-γRα expression upregulated by rhIFN-γ(both P＜0.05).The expression of pJAK2 induced bv rhIFN-γ was also suppressed by triptolide at the concentrations of 10-9 moI/L and 10-8 mol/L(both P＜0.05).The inhibition of triptolide on IFN-γRα and pJAK2 expression was dose-dependent and the 50%inhibitory concentrations(IC50 value)were 1.37×10-8 mol/L and 2.83×10-9 mol/L,respectively.On the contrary,triptolide upregulated the expression of SOCS1 stimulated by rhIFN-γ at the concentrations of 10-10,10-9 and 10-8 mol/L(P＜0.05,0.05,0.01,respectively)with the 50%effective dosage(ED50 value)at 3.32 × 10-11 mol/L.Conclusions By inhibiting the expression of IFN-γRα as well as phosphorylation of JAK2 and upregulating the expression of SOCS1,triptolide inhibits the phosphorylation of STAT-1,resulting in the inhibition of genetic transcription of multiple inflammatory factors induced by IFN-γ signaling in HaCaT keratinocytes,and the inhibition probably contributes to the efficacy of triptolide in the treatment of IFN-γ-dependent inflammatory skin disorders,such as psoriasis.
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Objective To investigate the mRNA expressions of IFN-gamma receptor and TNF-alpha receptor in peripheral blood mononuclear cells (PBMCs) of patients with psoriasis vulgaris and their role in the pathogenesis of psoriasis. Methods Fifty patients with psoriasis vulgaris (37 cases of active psoriasis and 13 cases of stable psoriasis) and 24 healthy human controls were included in this study. PBMCs were isolated from blood samples obtained from all patients and controls. The mRNA expressions of IFN-gamma receptor and TNF-aipha receptor in PBMCs were detected by RT-PCR. The disease severity in patients was evaluated by psoriasis area and severity index (PASI). Results The mRNA expressions of IFN-gamma receptor and TNF-alpha receptor were observed in the PBMCs of all subjects. The mRNA expression levels of IFN-gamma receptor were 0.72 ± 0.17 in healthy controls, 1.11 ± 0.55 in all patients with psoriasis, 1.13 ±0.57 in patients with active psoriasis and 1.03 ± 0.52 in patients with stable psoriasis, respectively. A signifi-cant increase was observed in the expression levels of IFN-gamma receptor mRNA in all psoriatic patients and in patients with active psoriasis compared with those in healthy controls (both P < 0.05), but there was no significant difference between the healthy controls and patients with stable psoriasis (P ＞ 0.05). The expres-sion levels of TNF-alpha receptor mRNA were 2.05 ± 1.34 in healthy controls, 2.70 ± 3.80 in all psoriatic patients, 2.90 ± 4.40 in patients with active psoriasis, 2.14 ± 1.05 in patients with stable psoriasis, respectively;there was no significant difference between psoriatic patients and healthy controls (P ＞ 0.05). However, no correlation was found between the mRNA expression of IFN-gamma receptor, that of TNF-alpha receptor,and disease severity in psoriatic patients. Conclusions The mRNA expression of IFN-gamma receptor in PBMCs is up-regulated in patients with psoriasis vulgaris, which is unrelated to the activity of psoriasis.
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Objective To assess the association between the amino acid polymorphism (Arg64Gln)within the interferon-γ receptor 2 gene (IFN-γR2) and psoriasis vulgaris in Chinese Hans. Methods Blood samples were collected from 182 patients with psoriasis vulgaris and 114 healthy human controls in Jiangsu and Anhui provinces. The amino acid polymorphism (Arg64Gin) within the IFN- γR2 was examined by PCR-restriction fragment length polymorphism (RFLP) and DNA sequencing. Results No significant difference was observed in the amino acid polymorphism (Arg64GIn) within the IFN-γR2 between the psoriatic patients and healthy controls (P > 0.05 ). There was a significant difference between patients with nail involvement and those without in the frequency of Gln64/Gln64 genotype (57.5% vs 38.1%, X~2= 5.33, P < 0.05),andArg64 (Gln64)allele [19.3% (80.7%)vs30% (70%), X~2=5.03, P < 0.05]. The frequencies of Gln64/Arg64 genotype and Gln64/Gln64 genotype in psoriatic patients with nail involvement significantly differed from those in the controls (29.8% vs 49.1%,X~2 = 5.48, P < 0.05; 57.5% vs 35.1%, X~2= 6.23, P <0.05 ), while no significant difference was found between the psoriatic patients without nail involvement and controls. Moreover, significant difference was noted between patients with prior upper respiratory tract infection (as inducements) and those without in the frequency of Arg64/Arg64 genotype (33.3% vs 15.5%, X~2 =4.94, P < 0.05) and Gln64 (Arg64) allele [51.9% (48.1%) vs 35.2% (64.8%), X~2= 5.46, P < 0.05]. Condusion The amino acid polymorphism (Arg64Gln) within the IFN-γR2 may be associated with the nail involvement and upper respiratory tract infection in patients with psoriasis vulgaris.
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Objective To study the influence of NS4B on host defense system. Methods After cell line stably expressed NS4B was established, cell expression profiling caused by NS4B was studied using DNA microarray, and the results of microarray were verified via IFNGR1 fluorescence intensity analysis. Results The data showed that HCV-NS4B could suppress host defense system-associated gene ex-pression, in particular, IFN-γsignal transduction-related genes. Conclusion NS4B could play a role in persistence and resistance to IFN therapy in HCV infection.