Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study was performed to estimate association of the Ile50Val polymorphism in IL4RA and clinical characteristics of chronic viral hepatitis including course of disease manifestation which is determined by degree of hepatic fibrosis. The group under investigation included 61 patient diagnosed with chronic viral hepatitis. Control group consisted of 128 randomly selected inhabitants of Tomsk city. Genotyping of Ile50Val polymorphism in the groups was performed by RFLP (restriction fragment length polymorphism) analysis. There was no significant differences in genotypes and alleles frequencies between cases and controls. However differences in genotype distribution depend on fibrosis stage were detected. Ile/Val heterozygote frequency in subgroup of patients without hepatic fibrosis was lower (7.1%) than in controls (51.6%) (p = 0.002) due to increase of both homozygote classes. Subgroup of patients without hepatic fibrosis differed by genotype frequencies both from patients with moderate and severe disease stage (p = 0.035; p = 0.004).
Mol Biol (Mosk)
PMID:[Association study of the Ile50Val polymorphism of interleukin-4 receptor gene (IL4RA) with chronic viral hepatitis]. 1598 67

Gastrointestinal malignancies account for about 20% of all cancers worldwide. It is widely accepted that cancer evolves through several stepwise morphological stages such as the adenoma-carcinoma and hyperplastic polyp-serrated adenoma-carcinoma sequences in colorectal cancers, and the metaplasia-dysplasia-carcinoma sequences in esophageal and gastric cancers. The morphological progression is associated with the accumulation of multiple genetic and epigenetic events. It is now recognized that epigenetic silencing of gene expression by CpG island methylation is an important alternative mechanism of inactivating tumor suppressor genes. Inflammatory conditions of the gastrointestinal and pancreaticobiliary tracts and liver such as Barrett esophagus, Helicobacter pylori gastritis, inflammatory bowel disease and viral hepatitis, are associated with increased frequency of malignancies and CpG methylation. In addition, CpG methylation is present in aberrant crypt foci and pancreatic intraepithelial neoplasia that are considered putative precursors of colon and pancreatic carcinomas, respectively. Understanding of these early genetic and epigenetic changes allows for the discoveries of potential screening, monitoring and therapeutic strategies. Targeting of the epigenetic changes that occur before the development of frank malignancy offers a potential chemopreventive strategy.
Curr Mol Med 2006 Jun
PMID:CpG island methylation in precursors of gastrointestinal malignancies. 1690 Jun 63

Initially described for their antiviral activities, type I Interferons are now recognized as central regulatory elements of the immune response, primarily for their effect on the differentiation of monocytes into dendritic cells and osteoclasts. They are routinely used in clinic for the treatment of several diseases, including viral hepatitis, multiple sclerosis and several forms of cancer. Interferons are however not devoid of toxic effects when high doses are administered to patients, indicating that interferon action must be timely and spatially down regulated. We review here the molecular mechanisms which have been described to shut off the interferon initiated signals.
Cell Mol Biol (Noisy-le-grand) 2006 May 15
PMID:Negative regulation of type I interferon signaling: facts and mechanisms. 1691 99

The complement system plays an important role in mediating both acquired and innate responses to defend against microbial infection, and in disposing immunoglobins and apoptotic cells. The liver (mainly hepatocytes) is responsible for biosynthesis of about 80-90% of plasma complement components and expresses a variety of complement receptors. Recent evidence from several studies suggests that the complement system is also involved in the pathogenesis of a variety of liver disorders including liver injury and repair, fibrosis, viral hepatitis, alcoholic liver disease, and liver ischemia/reperfusion injury. In this review, we will discuss the potential role of the complement system in the pathogenesis of liver diseases.
Cell Mol Immunol 2006 Oct
PMID:The complement system in liver diseases. 1709 30

Fulminant hepatitis in Asian pregnant women is generally caused by hepatitis E virus infection, and extremely high mortality is most common in them. Decreased cell-mediated immunity is considered a major cause of death in these cases, but what exactly influences decreased immunity and high mortality specifically during pregnancy is not known. We used electrophoretic mobility shift assays, immunoblotting, and immunohistochemical analysis to study the expression and DNA binding activity of NF-kB p50 and NF-kB p65 in pregnant fulminant hepatic failure (FHF) patients and compared them with their nonpregnant counterparts. In both PBMC and postmortem liver biopsy specimens the DNA-binding activity of NF-kB was very high in samples from pregnant FHF patients compared with those from nonpregnant women as well as pregnant women with acute viral hepatitis (AVH) without FHF. Further dissection of the NF-kB complex in supershift assays demonstrated complete absence of p65 in the NF-kB complex, which is formed by homodimerization of the p50 component in pregnant FHF patients. Western blotting and immunohistochemical analysis of the expression of p50 and p65 proteins both showed higher levels of p50 expression and a complete absence or a minimal expression of p65, indicating its nonparticipation in NF-kB-dependent transactivation in pregnant FHF patients. We suggest that the exclusion of p65 from the NF-kB transactivation complex seems to be a crucial step that may cause deregulated immunity and severe liver damage, leading to the death of the patient. Our findings provide a molecular basis, for developing novel therapeutic approaches.
Mol Med
PMID:Selective suppression of NF-kBp65 in hepatitis virus-infected pregnant women manifesting severe liver damage and high mortality. 1766 Aug 62

Among the noninvasive alternatives to liver biopsy, several studies have demonstrated the predictive value and a better benefit-to-risk ratio than biopsy of five combinations of simple serum biochemical markers (the super combination being FibroMAX (BioPredictive, Paris, France) in patients at risk of chronic liver diseases: FibroTest (BioPredictive) for the quantitative assessment of fibrosis; SteatoTest (BioPredictive) for the quantitative assessment of steatosis; ActiTest (BioPredictive) for the quantitative assessment of necroinflammatory activity in chronic viral hepatitis C and B; NashTest (BioPredictive) for the categorical diagnosis of nonalcoholic steatohepatitis; and AshTest for the quantitative assessment of alcoholic steatohepatitis (also known in the USA as HCV-FibroSURE, HBV-FibroSURE, ASH-FibroSURE and NASH-FibroSURE; LabCorp, NC, USA). The possible causes of false-negative and false-positive results are also better identified. These tests, which are now available in 50 countries, can facilitate the screening and management of the most frequent liver diseases.
Expert Rev Mol Diagn 2007 Sep
PMID:FibroMAX: towards a new universal biomarker of liver disease? 1789 56

Recent studies demonstrate that tissue microenvironments may regulate development and functions of immune cells including dendritic cells, monocytes and T cells. However, there is no report about functional regulation of innate NK cells by tissue microenvironment. The liver is an organ abundant in NK cells and susceptible to virus infection. The number and cytotoxicity of liver NK cells have been shown to be increased during pathogenesis of viral hepatitis and contribute to liver damage. So, whether and how liver stromal microenvironment regulates NK cells need to be fully investigated. By preparing liver fibroblast stromal cells to mimic stromal microenvironment in liver, in this study we demonstrate that liver stroma could chemoattract and adhere TLR3-triggered NK cells, and further augment the cytotoxicity and IFN-gamma production of TLR3-triggered NK cells via fibronectin. Furthermore, the autocrined IFN-gamma from NK cells is required for the enhancement of TLR3-triggered NK cell activation by liver stroma. Our results suggest that liver stroma can recruit NK cells and promote activation of NK cells during viral infection, thus providing a mechanistic explanation for the increased number and cytotoxicity of liver NK cells which may cause liver damage during pathogenesis of viral hepatitis.
Mol Immunol 2008 May
PMID:Liver stroma enhances activation of TLR3-triggered NK cells through fibronectin. 1838 80

Immune-mediated liver diseases including autoimmune and viral hepatitis are a major health problem worldwide. Natural cannabinoids such as Delta(9)-tetrahydrocannabinol (THC) effectively modulate immune cell function, and they have shown therapeutic potential in treating inflammatory diseases. We investigated the effects of THC in a murine model of concanavalin A (ConA)-induced hepatitis. Intraperitoneal administration of THC after ConA challenge inhibited hepatitis as shown by significant decrease in liver enzymes and reduced liver tissue injury. Furthermore, THC treatment resulted in significant suppression of crucial inflammatory cytokines in ConA-induced hepatitis. It is noteworthy that THC treatment in ConA-injected mice led to significant increase in absolute number of Forkhead helix transcription factor p3+ T regulatory cells in liver. We were surprised to find that select cannabinoid receptor (CB1 or CB2) agonists were not able to block hepatitis either independently or in combination. However, CB1/CB2 mixed agonists were able to efficiently attenuate hepatitis similar to THC. The modulatory effect of THC in ConA-induced hepatitis was reversed by both CB1 and CB2 antagonists. We also observed that endogenous cannabinoid anandamide was able to reduce hepatitis by suppressing cytokine levels. In addition, deficiency or inhibition of endocannabinoid hydrolyzing enzyme fatty acid amide hydrolase (FAAH), which leads to increased levels of endogenous cannabinoids, resulted in decreased liver injury upon ConA challenge. Our data demonstrate that targeting cannabinoid receptors using exogenous or endogenous cannabinoids and use of FAAH inhibitors may constitute novel therapeutic modalities to treat immune-mediated liver inflammation.
Mol Pharmacol 2008 Jul
PMID:Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: involvement of regulatory T cells. 1838 42

Protective measures against occupational exposure to the hepatitis B virus (HBV) and hepatitis C virus (HCV) must be taken in order to prevent infection in dental care workers. To determine the best way to protect these workers, our study examined viral hepatitis infection in dental care workers in regions with a high prevalence of HCV infections in Japan. In total, 141 dental care workers (including dentists, dental hygienists and dental assistants) were enrolled. After a questionnaire to elicit demographic information was administered by an oral surgeon, hepatitis B surface antigen (HBsAg), antibody to HBs (anti-HBs), antibody to hepatitis B core antigen (anti-HBc) and antibody to HCV (anti-HCV) were measured. When necessary, HBeAg, anti-HBe, levels of HBV DNA, anti-HBc IgM and HCV RNA in serum were measured. Of the dental care workers included, 68 (48.2%) had been immunized with a HBV vaccine. Only 9 wore a new pair of gloves for each new patient being treated, 36 changed to a new pair only after the old gloves were torn and 24 did not wear any gloves at all. No one was positive for HBsAg or anti-HCV, though 73 (51.8%) and 17 (12.1%) workers were respectively positive for anti-HBs and anti-HBc. The positive rate of anti-HBc varied directly with worker age and experience. Of the 68 workers immunized with HBV vaccine, 51 (75%) were positive for anti-HBs. Of the 63 workers who were not so immunized, 17 (27%) were positive for anti-HBs and 15 of these were also positive for anti-HBc. Immunized workers were more protected against HBV infection than non-immunized workers, indicating that HBV vaccine was a useful measure for protection against the infection. The anti-HBc positive rate was significantly higher among dental care workers than general blood donors, suggesting that frequency of exposure to HBV was greater in dental care workers. HBV vaccination should be made compulsory for all dental care workers who handle sharp instruments.
Int J Mol Med 2008 Jun
PMID:HBV and HCV infection in Japanese dental care workers. 1850 74

Association study was performed for genetic polymorphisms IL4 C(-590)T, IL4RA Ile50Val, TNF G(-308)A, to estimate their effect on quantitative features which are pathogenetically important for chronic viral hepatitis course, i.e. levels of IL4, IL10, IL12, tumor necrosis factor alpha, fibronectin, collagenase, protease inhibitors, macroglobulines, elastases, free and protein-bound hydroxyproline. It has been shown that A allele of TNF G(-308)A polymorphism is associated with decreased TNF-alpha, increased IL4 and IL12, as well as with low level of protein-bound hydroxyproline. In addition, association of CT genotype of IL4 C(-590)T polymorphism and high level of protein-bound hydroxyproline has been identified.
Mol Biol (Mosk)
PMID:[Association of immune system gene polymorphisms with quantitative features which are pathogenetically important in chronic viral hepatitis]. 1861 Aug 32


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