Dataset Information

Comparison of ISG15, IL28B and USP18 mRNA levels in peripheral blood mononuclear cells of chronic hepatitis B virus infected patients and healthy individuals.

ABSTRACT:

Aim

The purpose of this study was to evaluate the expression level of Interferon-stimulated Gene 15 (ISG15), Interleukin28B (IL28B) or IFN-lambda-3 and Ubiquitin specific peptidase 18 (USP18) genes in Peripheral Blood Mononuclear Cells (PBMCs) of patients with chronic active and inactive hepatitis B in comparison with healthy individuals.

Background

Despite the presence of the vaccine for hepatitis B virus (HBV), it remains a public health challenge. The effort to uncover the immune genes attributed to infection outcome is going through.

Methods

This Cross-sectional study was conducted on hepatitis B infected patients that were admitted to the Clinic of Liver diseases, Shiraz, January-November 2016. Patients were divided into two groups including active and inactive chronic regarding relevant World Gastroenterology Organization Global Guideline. They were mono-infected with HBV, and HCV or HIV co-infection was excluded from the study. Gene expression analysis was performed on fresh PBMCs samples with the help of Real-time PCR method.

Results

Interleukin 28B gene expression showed no statistically significant difference between the three studied groups (P>0.05). The expression level of ISG15 was significantly higher in the healthy control group compared to active (P= 0.0068) and inactive chronic subjects (P<0.0001). Similarly, USP18 expression level in the control group was also significantly higher compared to the active (P= 0.0228) and inactive chronic patients (P=0. 0226).

Conclusion

The results of this study showed that the expression level of ISG15 and USP18 but not IL28B were higher in healthy individuals than in those infected with HBV. This difference expression may highlight the role of ISG15 and USP18 in the immune-related mechanism of HBV infection.

SUBMITTER: Hashemi SMA

PROVIDER: S-EPMC6441482 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Comparison of ISG15, IL28B and USP18 mRNA levels in peripheral blood mononuclear cells of chronic hepatitis B virus infected patients and healthy individuals.

Hashemi Seyed Mohammad Ali SMA Sarvari Jamal J Fattahi Mohammad Reza MR Dowran Razieh R Ramezani Amin A Hosseini Seyed Younes SY

Gastroenterology and hepatology from bed to bench 20190101 1

<h4>Aim</h4>The purpose of this study was to evaluate the expression level of Interferon-stimulated Gene 15 (ISG15), Interleukin28B (IL28B) or IFN-lambda-3 and Ubiquitin specific peptidase 18 (USP18) genes in Peripheral Blood Mononuclear Cells (PBMCs) of patients with chronic active and inactive hepatitis B in comparison with healthy individuals.<h4>Background</h4>Despite the presence of the vaccine for hepatitis B virus (HBV), it remains a public health challenge. The effort to uncover the immu ...[more]

PMID: 30949318

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Project description:BACKGROUND:IL28B polymorphism is recognized as one of the most prominent predictors of hepatitis C spontaneous and treatment-induced clearance. Interestingly, the favorable genotypes of IL28B are found to be more frequent in Asian ethnicity than Caucasian and African populations, respectively. A few studies reported that there is a mysterious association between the IL28B polymorphism and the hepatitis C virus (HCV) genotype in patients with chronic hepatitis C but they did not give any reason for this phenomenon. OBJECTIVES:The foremost purpose of this study was to compare the distribution of IL28B genotypes between Iranian healthy individuals and patients with chronic hepatitis C. PATIENTS AND METHODS:In this study, 921 patients with chronic hepatitis C and 142 healthy individuals were included. The IL28B rs12979860 and rs8099917 polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS:The frequency of IL28B rs12979860 CC, CT, and TT genotypes in chronic hepatitis C patients was 38%, 48.8%, and 13.2% and in healthy individuals was 43.7%, 48.6%, and 7.7%. Also, the frequency of IL28B rs8099917 TT, GT, and GG genotypes in chronic hepatitis C patients was 58.3%, 37.1%, and 4.6% and in healthy individuals was 64.1%, 32.4% and 3.5%. The differences in the distribution of IL28B rs12979860 and rs8099917 genotypes between patients with chronic hepatitis C and healthy individuals were not statistically significant. When we compared the distribution of IL28B genotypes between the healthy group and the HCV infected patients by HCV genotype, we found 9.8% higher frequency of rs12979860 CC genotype in the healthy individuals than HCV genotype 1 infected patients (P = 0.03) however there was no significant difference in the distribution of rs12979860 genotypes between the healthy and HCV genotype 3 infected groups (P = 0.46). CONCLUSIONS:It seems that the impact of IL28B polymorphism on the spontaneous clearance of HCV genotype 1 is more prominent than HCV genotype 3 which results in the observation of higher rs12979860 C allele frequency in chronic hepatitis C patients with HCV genotype 3 than HCV genotype 1.

Project description:The interferon (IFN)-stimulated gene product 15 (ISG15) represents an ubiquitin-like protein (Ubl), which in a process termed ISGylation can be covalently linked to target substrates via a cascade of E1, E2, and E3 enzymes. Furthermore, ISG15 exerts functions in its free form both, as an intracellular and as a secreted protein. In agreement with its role as a type I IFN effector, most functions of ISG15 and ISGylation are linked to the anti-pathogenic response. However, also key roles in other cellular processes such as protein translation, cytoskeleton dynamics, exosome secretion, autophagy or genome stability and cancer were described. Ubiquitin-specific protease 18 (USP18) constitutes the major ISG15 specific protease which counteracts ISG15 conjugation. Remarkably, USP18 also functions as a critical negative regulator of the IFN response irrespective of its enzymatic activity. Concordantly, lack of USP18 function causes fatal interferonopathies in humans and mice. The negative regulatory function of USP18 in IFN signaling is regulated by various protein-protein interactions and its stability is controlled via proteasomal degradation. The broad repertoire of physiological functions and regulation of ISG15 and USP18 offers a variety of potential intervention strategies which might be of therapeutic use. Due to the high mutation rates of pathogens which are often species specific and constantly give rise to a variety of immune evasion mechanisms, immune effector systems are under constant evolutionarily pressure. Therefore, it is not surprising that considerable differences in ISG15 with respect to function and sequence exist even among closely related species. Hence, it is essential to thoroughly evaluate the translational potential of results obtained in model organisms especially for therapeutic strategies. This review covers existing and conceptual assay systems to target and identify modulators of ISG15, ISGylation, USP18 function, and protein-protein interactions within this context. Strategies comprise mouse models for translational perspectives, cell-based and biochemical assays as well as chemical probes.

Dataset Information

Comparison of ISG15, IL28B and USP18 mRNA levels in peripheral blood mononuclear cells of chronic hepatitis B virus infected patients and healthy individuals.

Aim

Background

Methods

Results

Conclusion

Publications

Comparison of ISG15, IL28B and USP18 mRNA levels in peripheral blood mononuclear cells of chronic hepatitis B virus infected patients and healthy individuals.

Similar Datasets

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