The Effects of Pathogen-Associated Molecular Patterns on Peripheral Blood Monocytes in Patients with Non-alcoholic Fatty Liver Disease.

Background: Innate immune responses to gut-derived pathogen-associated molecular patterns (PAMPs) have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Whether NAFLD patients have increased sensitivity to PAMP exposure has yet to be reported.

Methods: Peripheral blood mononuclear cell (PBMC)/monocytes were exposed to lipopolysaccharide (LPS), Pam3CSK4, or BSA conjugated palmitate .

Pro-Inflammatory Signaling Upregulates a Neurotoxic Conotoxin-Like Protein Encrypted Within Human Endogenous Retrovirus-K.

Motor neuron degeneration and spinal cord demyelination are hallmark pathological events in Amyotrophic Lateral Sclerosis (ALS). Endogenous retrovirus-K (ERVK) expression has an established association with ALS neuropathology, with murine modeling pointing to a role for the ERVK envelope () gene in disease processes. Here, we describe a novel viral protein cryptically encoded within the ERVK transcript, which resembles two distinct cysteine-rich neurotoxic proteins: conotoxin proteins found in marine snails and the Human Immunodeficiency Virus (HIV) Tat protein.

Plasma Oxylipins Levels in Nonalcoholic Fatty Liver Disease.

Background: Activation of innate immunity by gut-derived immunogens such as lipopolysaccharides (LPS) may play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Whether NAFLD-associated lipid disturbances and polyunsaturated fatty acid (PUFA) metabolism in particular contribute to heightened innate immunity, remains to be determined.

Objective: To determine if oxylipins, metabolic products of PUFA metabolism, enhance innate immune reactivity alone and/or following exposure to LPS.

The Impact of Gender on Interferon-Associated Depression and Anxiety.

Population studies indicate women have higher prevalences of depression and anxiety than men. Interferon (IFN) is a biologic agent that can induce or exacerbate depression and/or anxiety. Whether women are more likely to experience these side effects of IFN during treatment remains to be determined.

The Influence of Hepatitis C Viral Loads on Natural Killer Cell Function.

Background: Hepatitis C virus (HCV) infection has a high rate of chronicity, attributable to its capacity to alter host immunity, including natural killer (NK) cell function. In this study, the interaction between NK cell activity and HCV viral load was investigated.

Methods: Peripheral blood NK cells were examined for cytotoxicity and interferon (IFN)-γ expression in HCV infected low (LVL, < 800,000 IU/mL, n = 10) and high (HVL, > 800,000 IU/mL, n = 13) viral load patient cohorts.

Involvement of fibrinolytic regulators in adhesion of monocytes to vascular endothelial cells induced by glycated LDL and to aorta from diabetic mice.

Diabetes mellitus accelerates the development of atherosclerotic cardiovascular diseases. Monocyte adhesion is an early cellular event of atherogenesis. Elevated levels of glyLDL were common in diabetic patients.

Baseline Comorbidities Enhance the Risk of Treatment-Induced Depression in HCV-Infected Men: A Pilot Study.

Background: Hepatitis C virus (HCV) infection is associated with clinical depression,a condition that is aggravated on interferon-based therapy. In HCV infection, men often appear more resilient to depression than women. However, men are subject to depression in diseases that tend to be comorbid in HCV-infected.

Preliminary analysis of immune activation in early onset type 2 diabetes.

Introduction: First Nations and other Aboriginal children are disproportionately affected by cardiometabolic diseases, including type 2 diabetes (T2D). In T2D, the disruption of insulin signalling can be driven by pro-inflammatory immunity. Pro-inflammatory responses can be fueled by toll-like receptors (TLR) on immune cells such as peripheral blood mononuclear cells (PBMC, a white blood cell population).

Distribution of viral hepatitis in indigenous populations of North America and the circumpolar Arctic.

The burden of viral hepatitis among indigenous populations of the United States, Canada and Greenland is greater than in non-indigenous populations. In particular, throughout the circumpolar Arctic regions, chronic hepatitis B infection is highly prevalent, although incidence rates have declined considerably in certain regions due to infant HBV vaccination. Unique HBV (sub)genotypes having distinct clinical outcomes and distribution patterns are also observed within this region.

Hepatitis C virus in American Indian/Alaskan Native and Aboriginal peoples of North America.

Liver diseases, such as hepatitis C virus (HCV) infection, are "broken spirit" diseases. The prevalence of HCV infection for American Indian/Alaskan Native (AI/AN) in the United States and Canadian Aboriginals varies; nonetheless, incidence rates of newly diagnosed HCV infection are typically higher relative to non-indigenous people. For AI/AN and Aboriginal peoples risk factors for the diagnosis of HCV infection can reflect that of the general population: predominately male, a history of injection drug use, in midlife years, with a connection with urban centers.

Activation of β-adrenergic receptors increases the in vitro migration of malignant hepatocytes.

Aim:   Activation of adrenergic receptors (AR) has been reported to enhance the growth and invasion of various malignancies. The effects of AR agonists on malignant hepatocyte proliferation and migration have yet to be determined.

Methods:   PLC/PRF/5 (PLC) and Huh-7 cells were exposed to a wide range of concentrations of the AR agonists noradrenaline (NA) and isoprenaline.

GABA-B receptor activation inhibits the in vitro migration of malignant hepatocytes.

There are conflicting data regarding whether activation of γ-aminobutyric acid-B (GABA-B) receptors results in inhibition of tumor growth and invasion. The objectives of this study were to document the effects of the GABA-B receptor agonist baclofen on malignant hepatocyte proliferation and migration. We also sought to determine whether any effects on cell migration were mediated by changes in cyclic adenosine monophosphate (cAMP) signaling or matrix metalloproteinase (MMP) expression.

The potential influence of KIR cluster profiles on disease patterns of Canadian Aboriginals and other indigenous peoples of the Americas.

Genetic differences in immune regulators influence disease resistance and susceptibility patterns. There are major health discrepancies in immune-mediated diseases between Caucasians and Canadian Aboriginal people, as well as with other indigenous people of the Americas. Environmental factors offer a limited explanation as Aboriginal people also demonstrate a rare resistance to chronic hepatitis C virus infection.

Impact of aboriginal ethnicity on HCV core-induced IL-10 synthesis: interaction with IL-10 gene polymorphisms.

Unlabelled: The host immune response is a critical determinant in viral infection outcome. Epidemiological studies indicate that North American indigenous peoples are more resistant to chronic HCV infection than other populations. Due to the prominence of IL-10 in chronic HCV infection, we investigated the genetic tendency to produce IL-10 in Caucasian (CA) and First Nation (FN) populations.

Prevention of allergen-specific, Th2-biased immune responses in vivo: role of increased IL-12 and IL-18 responsiveness.

The factors that control development of adaptive responses to exogenous Ag remain incompletely understood. An ability to selectively direct immunity toward a specific phenotype would be of clinical benefit in numerous immunological disorders. Administration of chemically modified allergen glutaraldehyde-polymerized OVA (OA-POL) leads to >90% reductions in murine IgE and >500-fold increases in IgG2c responses that develop upon subsequent immunization with native Ag.

In vivo IgE levels in exogenous antigen stimulated responses: measurement of total IgE as a valid, simple surrogate for Ag-specific IgE.

Due to its dependence on IL-4 and IL-13 production, IgE production is frequently used to assess the type 2 character of an immune effector response. It is particularly relevant to measure IgE in murine models of immediate hypersensitivity, as allergen specific IgE is a critical effector molecule in this process. Given the complexity of developing ELISAs to measure specific IgE, total IgE levels are often reported with the implicit assumption that this provides an accurate gauge of specific IgE responses.

Differential regulation of innate and adaptive immune responses in viral encephalitis.

Viral encephalitis is a global health concern. The ability of a virus to modulate the immune response can have a pivotal effect on the course of disease and the fate of the infected host. In this study, we sought to understand the immunological basis for the fatal encephalitis following infection with the murine coronavirus, mouse hepatitis virus (MHV)-JHM, in contrast with the more attenuated MHV-A59.

Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology.

Differences in disease outcome between the highly neurovirulent MHV-JHM and mildly neurovirulent MHV-A59 have been attributed to variations within the spike (S) glycoprotein. Previously, we found that MHV-JHM neurovirulence was marked by diminished expression of interferon-gamma (IFN-gamma) mRNA and a reduced presence of CD8 T cells in the CNS concomitant with heightened macrophage inflammatory protein (MIP)-1 transcript levels and greater macrophage infiltration relative to MHV-A59 infection. Here, the ability of the S and non-spike genes to regulate these immune responses was evaluated using chimeric viruses.

Antigen-specific versus total immunoglobulin synthesis: total IgE and IgG1, but not IgG2a levels predict murine antigen-specific responses.

Background: Induction of an effective antibody (Ab) response requires delivery of multiple signals to B cells. Cross-linking of the B cell antigen receptor (BCR), signaling through CD40 and CD80/86 and cytokine signals combine to induce class switching and expression of specific isotypes. These signals are principally derived from activated, antigen (Ag)-specific T cells.