			Home About us Contact

Processes Critical (process + critical)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Inhibition of the lymphotoxin pathway as a therapy for autoimmune disease

IMMUNOLOGICAL REVIEWS, Issue 1 2008
Jeffrey L. Browning
Summary: The lymphotoxin (LT) system is part of the tumor necrosis factor family and is required for lymph node development. It has provided a wonderful tool for the dissection of processes critical not only for lymphoid organ development but also the maintenance of the adult immune architecture and the formation of ectopic organized lymphoid tissues in chronically inflamed sites. A soluble lymphotoxin-, receptor-immunoglobulin (LT,R-Ig) fusion protein can block this pathway and is currently being tested in the treatment of autoimmune disease. This review focuses on the immunological consequences of combined LT and LIGHT inhibition with LT,R-Ig administration as distinct from the developmental biology. [source]

Alcohol and Hepatitis C Virus,Interactions in Immune Dysfunctions and Liver Damage

ALCOHOLISM, Issue 10 2010
Gyongyi Szabo
Hepatitis C virus infection affects 170 million people worldwide, and the majority of individuals exposed to HCV develop chronic hepatitis leading to progressive liver damage, cirrhosis, and hepatocellular cancer. The natural history of HCV infection is influenced by genetic and environmental factors of which chronic alcohol use is an independent risk factor for cirrhosis in HCV-infected individuals. Both the hepatitis C virus and alcohol damage the liver and result in immune alterations contributing to both decreased viral clearance and liver injury. This review will capture the major components of the interactions between alcohol and HCV infection to provide better understanding for the molecular basis of the dangerous combination of alcohol use and HCV infection. Common targets of HCV and alcohol involve innate immune recognition and dendritic cells, the critical cell type in antigen presentation and antiviral immunity. In addition, both alcohol and HCV affect intracellular processes critical for hepatocyte and immune cell functions including mitochondrial and proteasomal activation. Finally, both chronic alcohol use and hepatitis C virus infection increase the risk of hepatocellular cancer. The common molecular mechanisms underlying the pathological interactions between alcohol and HCV include the modulation of cytokine production, lipopolysaccharide (LPS)-TLR4 signaling, and reactive oxygen species (ROS) production. LPS-induced chronic inflammation is not only a major cause of progressive liver injury and fibrosis, but it can also contribute to modification of the tissue environment and stem cells to promote hepatocellular cancer development. Alteration of these processes by alcohol and HCV produces an environment of impaired antiviral immune response, greater hepatocellular injury, and activation of cell proliferation and dedifferentiation. [source]

ORIGINAL ARTICLE: The Transcriptome of the Fetal Inflammatory Response Syndrome

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010
Sally A. Madsen-Bouterse
Problem, The fetal inflammatory response syndrome (FIRS) is considered the counterpart of the systemic inflammatory response syndrome (SIRS), but similarities in their regulatory mechanisms are unclear. This study characterizes the fetal mRNA transcriptome of peripheral leukocytes to identify key biological processes and pathways involved in FIRS. Method of study, Umbilical cord blood from preterm neonates with FIRS (funisitis, plasma IL-6 >11 pg/mL; n = 10) and neonates with no evidence of inflammation (n = 10) was collected at birth. Results, Microarray analysis of leukocyte RNA revealed differential expression of 541 unique genes, changes confirmed by qRT-PCR for 41 or 44 genes tested. Similar to SIRS and sepsis, ontological and pathway analyses yielded significant enrichment of biological processes including antigen processing and presentation, immune response, and processes critical to cellular metabolism. Results are comparable with microarray studies of endotoxin challenge models and pediatric sepsis, identifying 25 genes across all studies. Conclusion, This study is the first to profile genome-wide expression in FIRS, which demonstrates a substantial degree of similarity with SIRS despite differences in fetal and adult immune systems. [source]

Developmental microRNA expression profiling of murine embryonic orofacial tissue

BIRTH DEFECTS RESEARCH, Issue 7 2010
Partha Mukhopadhyay
Abstract BACKGROUND: Orofacial development is a multifaceted process involving precise, spatio-temporal expression of a panoply of genes. MicroRNAs (miRNAs), the largest family of noncoding RNAs involved in gene silencing, represent critical regulators of cell and tissue differentiation. MicroRNA gene expression profiling is an effective means of acquiring novel and valuable information regarding the expression and regulation of genes, under the control of miRNA, involved in mammalian orofacial development. METHODS: To identify differentially expressed miRNAs during mammalian orofacial ontogenesis, miRNA expression profiles from gestation day (GD) -12, -13 and -14 murine orofacial tissue were compared utilizing miRXplore microarrays from Miltenyi Biotech. Quantitative real-time PCR was utilized for validation of gene expression changes. Cluster analysis of the microarray data was conducted with the clValid R package and the UPGMA clustering method. Functional relationships between selected miRNAs were investigated using Ingenuity Pathway Analysis. RESULTS: Expression of over 26% of the 588 murine miRNA genes examined was detected in murine orofacial tissues from GD-12,GD-14. Among these expressed genes, several clusters were seen to be developmentally regulated. Differential expression of miRNAs within such clusters wereshown to target genes encoding proteins involved in cell proliferation, cell adhesion, differentiation, apoptosis and epithelial-mesenchymal transformation, all processes critical for normal orofacial development. CONCLUSIONS: Using miRNA microarray technology, unique gene expression signatures of hundreds of miRNAs in embryonic orofacial tissue were defined. Gene targeting and functional analysis revealed that the expression of numerous protein-encoding genes, crucial to normal orofacial ontogeny, may be regulated by specific miRNAs. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc. [source]