Interferon-Stimulated Genes Response in Endothelial Cells Following Hantaan Virus Infection

The regulation mechanism of interferon (IFN) and IFN-stimulated genes is a very complex procedure and is dependent on cell types and virus species. We observed molecular changes related to anti-viral responses in endothelial cells during Hantaan virus (HTNV) infection. We found that there are two patterns of gene expression, the first pattern of gene expression being characterized by early induction and short action, as in that of type I IFNs,' and the other being characterized by delayed induction and long duration, as those of IRF-7, MxA, and TAP-1/2. Even though there are significant differences in their induction folds, we found that all of IFN-alpha/beta , IRF- 3/7, MxA, and TAP-1/2 mRNA expressions reached the peak when the viral replication was most active, which took place 3 days of post infection (d.p.i.). In addition, an interesting phenomenon was observed; only one gene was highly expressed in paired genes such as IFN-alpha/beta??(3/277-folds), IRF-3/7 (2.2/29.4-folds), and TAP- 1/2 (26.2/6.1-folds). Therefore, IFN-beta, IRF-7, and TAP-1 seem to be more important for the anti-viral response in HTNV infection. MxA was increased to 296-folds at 3 d.p.i. and kept continuing 207-folds until 7 d.p.i.. The above results indicate that IFN-beta works for an early anti-viral response, while IRF7, MxA, and TAP-1 work for prolonged anti-viral response in HTNV infection.

Short-Term High Expression of Interferon-Alpha Modulates Progression of Type 1 Diabetes in NOD Mice

Type I diabetes (T1D) is an organ-specific autoimmune disease caused by the T cell-mediated destruction of the insulin-producing beta cells in the pancreatic islets. The onset of T1D is the consequence of a progressive destruction of islet beta cells mediated by an imbalance between effector CD4+ T helper (Th)1 and regulatory CD4+ Th2 cell function. Since interferon-alpha (IFN-alpha) has been known to modulate immune function and autoimmunity, we investigated whether administration of adenoviral-mediated IFN-alpha gene would inhibit the diabetic process in NOD mice. The development of diabetes was significantly inhibited by a single injection of adenoviral-mediated IFN-alpha gene before 8 weeks of age. Next, we examined the hypothesis that Th2-type cytokines are associated with host protection against autoimmune diabetes, whereas Th1-type cytokines are associated with pathogenesis of T1D. The expression of IFN-alpha induced increase of serum IL-4 and IL-6 (Th2 cytokines) levels and decrease of serum IL-12 and IFN-gamma (Th1 cytokines) levels. Therefore, overexpression of IFN-alpha by adenoviral-mediated delivery provides modulation of pathogenic progression and protection of NOD mice from T1D.

Observation on Peg-IFN alpha-2? Combined with Capsule Ribavirin in Treatment Drug Addicts with Chronic Hepatitis C / 医学研究杂志

0.05).Conclusions Compared with the patients with Chronic Hepatitis C related to transfusionem,the efficiency of peg-IFN alpha-2b combined with ribavirin in treatment of IVDU with Chronic Hepatitis C was similar,and the therapy is a effective choice in treatment of IVDU with Chronic Hepatitis C.

IFN-alpha Downregulates ERK Phosphorylation of CD4+ T Lymphocytes in Systemic Lupus Erythematosus / 대한류마티스학회지

OBJECTIVE: CD4+ T cells from patients with systemic lupus erythematosus (SLE) display aberrant TCR signaling and IFN-alpha plays critical roles in the pathogenesis of SLE; however, the effects of IFN-alpha on disease-associated TCR signaling defects remain unknown. This study investigated the ERK phosphorylation during TCR triggering and the effects of IFN-alpha on ERK signaling in CD4+ T cells. METHODS: CD4+ T lymphocytes were sorted from PBMC using magnetic beads in patients with SLE who met the 1982 revised ACR criteria for SLE and age-matched healthy controls. The phosphorylation of ERK 1/2 was analyzed by flow cytometry and mean fluorescent intensity was measured to define the degree of phosphorylation of ERK. In some experiments, anti-CD3 stimulation was performed after preincubation with patient or control serum, diluted in tissue culture media, with or without addition of an anti-IFN-alpha antibody. The serum level of IFN-alpha was measured by ELISA. RESULTS: ERK-1/2 phosphorylation was decreased in CD4+ T cells of lupus patients than healthy controls and associated with disease activity. Pre-incubation of control CD4+ T cells with allogeneic lupus plasma decreased ERK-1/2 phosphorylation more than allogeneic control and RA plasma and this was reversed by anti-IFN-alpha Ab. Accordingly, ERK-1/2 phosphorylation was decreased in control CD4+ T cells pre-incubation with lupus plasma with high IFN-alpha levels more than lupus plasma with non-detectable IFN-alpha levels. Recombinant IFN-alpha inhibited TCR-mediated ERK-1/2 phosphorylation dose-dependently. CONCLUSION: These results suggest that IFN-alpha stimulation in vivo may underlie the aberrant TCR-mediated MAPK signaling in lupus CD4+ T cells and associated with disease pathogenesis.

Detection of hepatitis B virus pre-C region mutation in cases of chronic hepatitis B and its relationship with IFN treatment / 中国实用内科杂志

Objective To investigate the relationship between hepatitis B virus pre-core region 1896 site mutation in cases of chronic hepatitis B and IFN-alpha treatment.Methods 200 patients with chronic hepatitis B were randomly divided into experimental group(n=100) and control group(n=100).The patients in experimental group were treated with regular liver-protective drugs and IFN-alpha,while Control group patients received only regular liver-protective drugs for 6 months.PCR-RFLP were used to detect hepatitis B virus(HBV)DNA with pre-C region 1896 site mutation in two grops pre and post treatment.Results The mutation rates before interferon treatment were 20%(20/100) and 18%(18/100) in experimental group and control group,respectly.After treatment,the effective rates in experimental group were 60%(12/20) and 50%(40/80) in Patients with Chronic Hepatitis B variant and wild strain virus Infection,respectly.The effective rate in experimental group was significantly higher than that in control group.Conclusion IFN-alpha therapy was not correlated with genomic variability of the core region.

Effects suramin, tumor necrosis factor-alpha(TNF-alpha, interferon-alpha(IFN-alpha on human renal carcinoma cell line growth / 대한비뇨기과학회지

Recently much interest has been expressed for the use of biological response modifiers and growth factor antagonists in the treatment or radiation and chemotherapeutic drug-refractory renal cell carcinoma. Herein antiproliferative effects of Suramin, human recombinanl tumor necrosis factor alpha (TNF-alpha) and human recombinant interferon alpha (IFN-alpha) as a single and in combination were studied in vito on human renal carcinoma cell line (Caki-1). Antiproliferative effect was evaluated by trypan blue dye exclusion assay after 3 days exposure to Suramin at 10, 30, 100, 300, 1,000 mcg/ ml. TNF-alpha at 1, 10, 50, 100, 500, 1,000 units/ml and IFN-alpha at 10, 100, 1,000. 10,000 units/ml concentration, respectively. In addition, effects of combined administration in tolerable peak plasma level or suramin (300 mcg/ml). TNF-alpha (500 units/ml) and IFN-alpha (1000 units/ml) were comparatively analyzed to those of single drug administration. The results were as follows: 1. Significant dose dependent antiproliferative effects were shown by Suramin at above 100 mcg/ml. TNF-alpha at above 500 units/ml and IFN-alpha at above 10 units/ml, respectively (p<0.05). 2. At peak plasma level, suramin, TNF-alpha and IFN-alpha showed less than 50% inhibition of proliferation. 3. On combined administration, suramin plus TNF-alpha (61.0%), Suramin plus IFN-alpha(71.7%) and TNF-alpha plus IFN-alpha (57.2%) induced significantly greater inhibition of proliferation (p<0.005). These results suggest that further in vivo study using combination of Suramin plus TNF-alpha Suramin plus IFN-alpha and TNF-alpha plus IFN-alpha is necessary and that these combination trials may become one of the treatment options for renal cell carcinoma.