OBJECTIVES: To investigate the effect of interferon-λ1 (IFN-λ1) on glucocorticoid (GC) resistance in human bronchial epithelial cells (HBECs) stimulated by respiratory syncytial virus (RSV). METHODS: HBECs were divided into five groups: control, dexamethasone, IFN-λ1, RSV, and RSV+IFN-λ1. CCK-8 assay was used to measure the effect of different concentrations of IFN-λ1 on the viability of HBECs, and the sensitivity of HBECs to dexamethasone was measured in each group. Quantitative real-time PCR was used to measure the mRNA expression levels of p38 mitogen-activated protein kinase (p38 MAPK), glucocorticoid receptor (GR), and MAPK phosphatase-1 (MKP-1). Western blot was used to measure the protein expression level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic ratio of GR was calculated. RESULTS: At 24 and 72 hours, the proliferation activity of HBECs increased with the increase in IFN-λ1 concentration in a dose- and time-dependent manner (P˂0.05). Compared with the RSV group, the RSV+IFN-λ1 group had significant reductions in the half-maximal inhibitory concentration of dexamethasone and the mRNA expression level of p38 MAPK (P<0.05), as well as significant increases in the mRNA expression levels of GR and MKP-1, the level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic GR ratio (P<0.05). CONCLUSIONS IFN-λ1 can inhibit the p38 MAPK pathway by upregulating MKP-1, promote the nuclear translocation of GR, and thus ameliorate GC resistance in HBECs.
Humans ; p38 Mitogen-Activated Protein Kinases/genetics* ; Glucocorticoids/pharmacology* ; Receptors, Glucocorticoid/analysis* ; Dual Specificity Phosphatase 1/physiology* ; Dexamethasone/pharmacology* ; Drug Resistance/drug effects* ; Respiratory Syncytial Viruses ; Interferons/pharmacology* ; MAP Kinase Signaling System/drug effects* ; Epithelial Cells/drug effects* ; Signal Transduction/drug effects* ; Cells, Cultured

Hepatitis B virus (HBV) infection is one of the most serious public health problems. HBV infection could lead to hepatitis B, and even further develop into hepatic cirrhosis and hepatocellular carcinoma. Interferon lambda (IFN-λ) is a member of the interferon (IFN) family and an important cytokine for antiviral defense. There are four members in IFN-λ family, including IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4. The genetic polymorphisms in the IFN-λ genes are associated with HBV replication and treatment response of HBV patients. In this review, we summarized the roles of genetic polymorphisms of the IFN-λ genes played in HBV infection, disease progression and treatment, with the aim to better understand their function. This review could serve as a reference for the HBV prevention and treatment of HBV patients, as well as for future clinical usage.
Antiviral Agents/pharmacology* ; Hepatitis B/genetics* ; Hepatitis B virus/genetics* ; Humans ; Interferons/pharmacology* ; Liver Neoplasms ; Polymorphism, Genetic ; Virus Replication/genetics*

OBJECTIVE: To study the effect of 5-aminoimidazole-4-formamide ribonucleotide (AICAR) combined with interferon (IFN-α-2b) on the proliferation and apoptosis of chronic myeloid leukemia K562 cells, and explore its possible mechanism. METHODS: CCK-8 method was used to detect the inhibition of cell proliferation. Wright Giemsa method was used to stain and cell morphology was observed by light microscopy. FITC Annexin V/PI double staining method was used to analyze the change of apoptosis rate. Immunocytochemistry method was used to detect the expression of wild-type P53 protein. RESULTS: Different concentration of AICAR was inhibitory effect on K562 cells at different time point of action for 24 h, 48 h, and 72 h, and the inhibition was time and dose-dependent (r=0.71, r=0.84). The combination of AICAR and IFN-α-2b could effectively inhibit the proliferation and promote apoptosis of K562 cells. The inhibition rate of K562 cells was (45.26±2.54)%, and the early apoptosis rate was (33.72±0.23)%, which was statistically significantly different from the control group, AICAR or IFN-ɑ-2b alone (P<0.05). The combination of two drugs promoted the expression of wild-type p53 protein. CONCLUSION AICAR and/or IFN-ɑ-2b can inhibit the cell proliferation and promote the apoptosis of K562 cells. The combination of two drugs shows synergistic antitumor effect, and its mechanism may be related to the promotion of high expression of wild-type p53 protein.
Apoptosis ; Cell Proliferation ; Formamides ; Humans ; Imidazoles ; Interferons ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Ribonucleotides/pharmacology*

OBJECTIVETo explore the inhibitory effect of thalidomide combined with interferon (IFN) on the human acute myeloid leukemia cell line Kasumi- 1 and its mechanism.

METHODSThe inhibitiory effect of Kasumi- 1 cells by thalidomide, interferon or combination was detected by CCK- 8 method, the apoptosis by flow cytometry, the expression of apoptosis related proteins by Western blot, vascular endothelial growth factor (VEGF) concentration in culture supernatant by ELISA.

RESULTSThalidomide inhibited the proliferation of Kasumi- 1 in a dose- dependent manner from 50 μg/ml to 500 μg/ml with an IC₅₀ of (451.13 ± 6.92）μg/ml at 24 h and (362.50 ± 14.52）μg/ml at 48 h. IFN also demonstrated the inhibitory capacity in a dose-dependent manner from 500 U/ml to 5 000 U/ml, with an IC₅₀ of (2 209 ± 127) U/ml at 24 h and (1 393±63) U/ml at 48 h. The apoptosis rates of Kasumi-1 cells treated with thalidomide 350 μg/ml or IFN 1 400 U/ml for 48 h were (14.68 ± 2.61) % and (21.71 ± 0.71)%, respectively, significantly higher than control group (P<0.01). In combination group the inhibition and the apoptosis rate were (88.50 ± 2.40) % and (41.95 ± 3.41)%, significantly higher than control and each single agent group (P<0.01). The VEGF concentrations of combination group [(94.61 ± 5.46) ng/L decreased significantly, as compared to thalidomide group [(141.11 ± 3.70) ng/L and IFN group [(119.90 ± 2.00) ng/L (P < 0.05). Western blot analysis showed Bcl-2 expression of Kasumi-1 cells decreased, while p-P38, Bax, cytochrome C, cleaved-Caspase-3, 8, 9 increased after treated with thalidomide 350 μg/ml or IFN 1 400 U/ml for 48 h. When treated with the combination agents, the expression of Bcl-2 further decreased and p-P38, Bax, cytochrome C, cleaved-Caspase-3, 8, 9 further increased as compared with each single agent (P < 0.05).

CONCLUSIONThalidomide and IFN could synergistically inhibit the proliferation of Kasumi-1 cells probably through inducing apoptosis via the mitochondrial pathway, death receptor pathway and P38 MAPK pathway, as well as inhibiting VEGF secretion.

Apoptosis ; Caspases ; metabolism ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Humans ; Interferons ; pharmacology ; Leukemia, Myeloid, Acute ; pathology ; MAP Kinase Signaling System ; Thalidomide ; pharmacology ; Vascular Endothelial Growth Factor A ; metabolism

Drug Resistance, Viral ; Endopeptidases ; Hepatitis B virus ; drug effects ; Hepatitis B, Chronic ; virology ; Humans ; Interferons ; pharmacology

Antiviral Agents ; pharmacology ; Hepatitis B virus ; drug effects ; Interferons ; pharmacology

OBJECTIVETo construct the recombinant HCV-1b replicon by replacing NS5A region using serum samples from patients with chronic hepatitis C (CHC) in South China and explore the biological characteristics of NS5A protein in response to antiviral therapy.

METHODSThe on-off plasmid containing the cutting sites of the restriction endonucleases MIu I and Bcl I was designed based on the backbone of robust HCV 1b replicon. The full-length fragments of HCV NS5A were amplified from different CHC patients by RT-PCR and cloned into pMD-18 vector, followed by sequence analysis of amino acid mutation of ISDR, PKRBD, V3 and IRRDR within the NS5A region. If the amplicon obtained contained no MIu I or Bcl I cutting sites, the NS5A fragment was re-amplified using primers containing the cutting sites and inserted into the replicon for replacement.

RESULTSThe full-length fragments of NS5A were obtained successfully from CHC patients. The core region of ISDR-V3 of NS5A was replaced in the HCV replicon plasmid and showed correct sequences. The amino acid mutations of ISDR and PKRBD within NS5A were more frequent in patients with sustained viral response (SVR) than those without SVR. A high variability in the amino acid sequence was observed in both IRRDR and V3 regions.

CONCLUSIONThe plug-in type recombinant HCV replicon for replacement of NS5A region in the virus from CHC patients has been successfully constructed, which provides a basis for further investigation of the biological characteristics of NS5A protein, the mechanisms of interferon-resistance, and antiviral therapy of difficult-to-treat CHC.

Amino Acid Sequence ; Antiviral Agents ; administration & dosage ; pharmacology ; Drug Resistance ; genetics ; Genetic Variation ; Genotype ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; drug therapy ; virology ; Humans ; Interferons ; administration & dosage ; pharmacology ; Molecular Sequence Data ; Recombination, Genetic ; Replicon ; genetics ; Sequence Analysis ; Viral Nonstructural Proteins ; genetics

OBJECTIVETo study the expression of gene associated with retinoid-interferon-induced mortality-19(GRIM-19) in preimplantation embryo of mice and explore its role in embryonic development.

METHODSThe protein and mRNA expressions of GRIM-19 in 2-cell, 4-cell, 8-cell, morula, and blastocyst phases of mice preimplantation embryo were detected by Western blot analysis and Real-time polymerase chain reaction (PCR).

RESULTSGRIM-19 was continuously expressed in every stage of preimplantation embryo of mice. Western blot analysis and Real-time PCR demonstrated a gradual increase of GRIM-19 expression from 2-cell, which reached a peak in 8-cell phase and then decreased progressively.

CONCLUSIONSThe expression of GRIM-19 in mouse preimplantation embryos changes as at different developmental phases. GRIM-19 may play an important role during embryonic development.

Animals ; Blastocyst ; drug effects ; metabolism ; Female ; Interferons ; pharmacology ; Mice ; NADH, NADPH Oxidoreductases ; genetics ; metabolism ; Pregnancy ; RNA, Messenger ; genetics ; Tretinoin ; pharmacology

OBJECTIVETo screen the mi-RNA expression profile after interferon treatment in cells infected with hepatitis C virus (HCV).

METHODSHuh-7.5.1 cells was infected with HCV by in vitro transcription and cultured with interferon. The mi-RNA microarray was used to measure the mi-RNA expression in the control group, HCV transcription group and interference group. Intra-group differences were analyzed by the 2 ((-delt delt CT)) method.

RESULTSWith mi-RNA expressed in normal Huh-7.5.1 cells as a benchmark, expressions of 13 kinds of mi-RNAs were up-regulated after HCV infection and then down-regulated following interferon treatment; 7 were down-regulated after HCV infection and then up-regulated following interferon treatment.

CONCLUSIONmi-RNA10a, mi-RNA21, mi-RNA149, mi-RNA152 and mi-RNA210 may be related to hepatitis C virus replication and transcription.

Cell Line, Tumor ; Gene Expression Profiling ; Hepacivirus ; genetics ; Humans ; Interferon-alpha ; pharmacology ; Interferons ; pharmacology ; MicroRNAs ; drug effects ; genetics ; RNA, Viral ; genetics ; Transfection

In addition to immune regulation, interferon could suppress hepatitis B virus (HBV) replication through direct antiviral effect. After binding with the receptors on cell membrane, interferon directly inhibits HBV at different steps in HBV replication cycle by activating cell signaling cascades such as JAK-STAT pathway, interferon regulatory factor (IRFs) signaling pathway, and so on, followed by inducing a series of cytokines which are involved in regulation of the function of HBV enhancer I / X promoter (Ehn I / Xp). Also, interferon could induce the host cells to produce anti-viral proteins. This review describes the direct antiviral mechanism of interferon on HBV.
Animals ; Antiviral Agents ; pharmacology ; Hepatitis B virus ; drug effects ; physiology ; Humans ; Interferons ; classification ; pharmacology ; Signal Transduction ; drug effects ; Virus Replication ; drug effects