miR-197 Expression in Peripheral Blood Mononuclear Cells from Hepatitis B Virus-Infected Patients
0
조회
0
다운로드
0
인용
0
참고문헌
초록
Background/Aims: This study aimed to investigate the microRNA (miRNA) expression profiles in peripheral blood mononuclear cell (PBMC) of hepatitis B virus (HBV)-infected patients with different clinical manifestations and to analyze the function of miR-197. Methods: PBMC miRNA expression profiles in 51 healthy controls, 70 chronic asymptomatic carriers,107 chronic hepatitis B patients, and 76 HBV-related acute on chronic liver failure patients were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). miR-197 mimic and inhibitor were transfected in THP-1 cells. qRT-PCR and ELISA for interleukin (IL)-18 mRNA and protein levels were performed, respectively. Results: The microarray analysis revealed that 17 PBMC miRNA expression profiles (12 miRNAs downregulated and five miRNAs upregulated)differed significantly in HBV-induced liver disease patients presenting with various symptoms. The qRT-PCR results suggested that the PBMC miR-197 levels regularly decreased as the severity of liver disease symptoms became aggravated. IL-18, a key regulator in inflammation and immunity, was inversely correlated with miR-197 levels. Bioinformatic analysis indicated that IL-18 was a target of miR-197. Exogenous expression of miR-197 could significantly repress IL-18 expression at both the mRNA and protein levels in THP-1 cells. Conclusions: We concluded that multiple PBMC miRNAs had differential expression profiles during HBV infection and that miR-197 may play an important role in the reactivation of liver inflammation by targeting IL-18.
Abstract
Background/Aims: This study aimed to investigate the microRNA (miRNA) expression profiles in peripheral blood mononuclear cell (PBMC) of hepatitis B virus (HBV)-infected patients with different clinical manifestations and to analyze the function of miR-197. Methods: PBMC miRNA expression profiles in 51 healthy controls, 70 chronic asymptomatic carriers,107 chronic hepatitis B patients, and 76 HBV-related acute on chronic liver failure patients were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). miR-197 mimic and inhibitor were transfected in THP-1 cells. qRT-PCR and ELISA for interleukin (IL)-18 mRNA and protein levels were performed, respectively. Results: The microarray analysis revealed that 17 PBMC miRNA expression profiles (12 miRNAs downregulated and five miRNAs upregulated)differed significantly in HBV-induced liver disease patients presenting with various symptoms. The qRT-PCR results suggested that the PBMC miR-197 levels regularly decreased as the severity of liver disease symptoms became aggravated. IL-18, a key regulator in inflammation and immunity, was inversely correlated with miR-197 levels. Bioinformatic analysis indicated that IL-18 was a target of miR-197. Exogenous expression of miR-197 could significantly repress IL-18 expression at both the mRNA and protein levels in THP-1 cells. Conclusions: We concluded that multiple PBMC miRNAs had differential expression profiles during HBV infection and that miR-197 may play an important role in the reactivation of liver inflammation by targeting IL-18.
참고문헌 (25)
- Chisari FV, "Pathogenesis of hepatitis B virus infection", Pathol Biol (Paris), 58, pp.258~266 (2010)
- Bartel DP, "icroRNAs: genomics, biogenesis, mechanism, and function", Cell, 116, pp.281~297 (2004)
- Bi Y, "MicroRNAs: novel regulators during the immune response", J Cell Physiol, 218, pp.467~472 (2009)
- Qiu L, "miR-122-induced down-regulation of HO-1 negatively affects miR-122-mediated suppression of HBV", Biochem Biophys Res Commun, 398, pp.771~777 (2010)
- Zhang X, "Modulation of hepatitis B virus replication and hepatocyte differentiation by microRNA-1", Hepatology, 53, pp.1476~1485 (2011)
- Ura S, "Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma", Hepatology, 49, pp.1098~1112 (2009)
- Murakami Y, "Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues", Oncogene, 25, pp.2537~2545 (2006)
- Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association, "The guidelines of prevention and treatment for chronic hepatitis B", Zhonghua Gan Zang Bing Za Zhi, 13, pp.881~891 (2005)
- Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Diseases and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association, "Diagnostic and treatment guidelines for liver failure", Zhonghua Gan Zang Bing Za Zhi, 14, pp.643~646 (2006)
- Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method", Methods, 25, pp.402~408 (2001)
- Otaegui D, "Differential micro RNA expression in PBMC from multiple sclerosis patients", PLoS One, 4, pp.e6309~ (2009)
- Hoekstra M, "The peripheral blood mononuclear cell microRNA signature of coronary artery disease", Biochem Biophys Res Commun, 394, pp.792~797 (2010)
- Pan XB, "Characterization of microRNA expression profiles associated with hepatitis B virus replication and clearance in vivo and in vitro", J Gastroenterol Hepatol, 27, pp.805~812 (2012)
- Tili E, "Modulation of miR-155 and miR-125b levels following lipopolysaccharide", TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock, 2007, pp.179, 5082~5089
- Huang B, "miR-142-3p restricts cAMP production in CD4+CD25- T cells and CD4+CD25+ TREG cells by targeting AC9 mRNA", EMBO Rep, 10, pp.180~185 (2009)
- Zhou B, "miR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely", Proc Natl Acad Sci U S A, 104, pp.7080~7085 (2007)
- Johnnidis JB, "Regulation of progenitor cell proliferation and granulocyte function by microRNA-223", Nature, 451, pp.1125~1129 (2008)
- Ji F, "Circulating microRNAs in hepatitis B virus-infected patients", J Viral Hepat, 18, pp.e242~e251 (2011)
- Weber F, "A limited set of human microRNA is deregulated in follicular thyroid carcinoma", J Clin Endocrinol Metab, 91, pp.3584~3591 (2006)
- Lehmann U, "Identification of differentially expressed microRNAs in human male breast cancer", BMC Cancer, 10, pp.109~ (2010)
- Estep M, "Differential expression of miRNAs in the visceral adipose tissue of patients with non-alcoholic fatty liver disease", Aliment Pharmacol Ther, 32, pp.487~497 (2010)
- Arola-Arnal A, "Proanthocyanidins modulate microRNA expression in human HepG2 cells", PLoS One, 6, pp.e25982~ (2011)
- Shinoda M, "Increased serum and hepatic tissue levels of interleukin-18 in patients with fulminant hepatic failure", J Gastroenterol Hepatol, 21, pp.1731~1736 (2006)
- Roth GA, "Pro-inflammatory interleukin-18 and caspase-1 serum levels in liver failure are unaffected by MARS treatment", Dig Liver Dis, 41, pp.417~423 (2009)
- Sun Y, "Effect of IL-18 on peripheral blood mononuclear cells of chronic hepatitis B and hepatitis B virus DNA released by HepG2.2.15 cell lines", Hepatobiliary Pancreat Dis Int, 3, pp.230~234 (2004)
