Cancer cells are commonly less differentiated than their normal progenitors; a phenotype that correlates with loss of specialized functions and an increased capability to self-renew. Melanoma is an ideal model to analyze cancer progression and differentiation since a well-characterized process of step-wise tumor progression has been defined. Our lab previously ...

The gram-negative rod Burkholderia pseudomallei is the causative agent of melioidosis, a potentially fatal disease which is endemic in tropical and subtropical areas. The bacterium multiplies intracellularly within the cytosol, induces the formation of actin tails, and can spread directly from cell to cell. Recently, it has been shown that ...

The immunity-related GTPases (IRG), also known as p47 GTPases, are a family of proteins that are tightly regulated by IFNs at the transcriptional level and serve as key mediators of IFN-regulated resistance to intracellular bacteria and protozoa. Among the IRG proteins, loss of Irgm1 has the most profound impact on ...

Interferon (IFN) is effective at inducing complete remissions in patients with chronic myelogenous leukemia (CML), and evidence supports an immune mechanism. Here we show that the type I IFNs (alpha and beta) regulate expression of the IFN consensus sequence-binding protein (ICSBP) in BCR-ABL-transformed cells and as shown previously for ICSBP, ...

Neuroinflammation plays an integral role in the progression of neurodegeneration. In this study we investigated the anti-inflammatory effects of different classes of flavonoids (flavanones, flavanols and anthocyanidins) in primary mixed glial cells. We found that the flavanones naringenin and hesperetin and the flavanols (+)-catechin and (-)-epicatechin, but not the anthocyanidins ...

Horses are hosts to two types of gammaherpesviruses, equine herpes virus (EHV) 2 and 5. While EHV-2 is ubiquitous in adult horses, EHV-5 has been less frequently described. Due to strong serological cross-reactivity, EHV-2 and -5 cannot be discriminated in broad spectrum antibody tests and are thus commonly referred to ...

Astrocytes can either exacerbate or ameliorate secondary degeneration at sites of injury in the CNS but the contextual basis for eliciting these opposing phenotypes is poorly understood. In this study, we demonstrate that the two major cytokines produced by Th1 and Th2 cells, interferon-gamma (IFN-gamma), and interleukin-4 (IL-4), respectively, contribute ...

OBJECTIVE: gamma-Tocotrienol is a major component of the tocotrienol-rich fraction of palm oil, but there is limited evidence that it has antitumor activity. In particular, the effects of gamma-tocotrienol on human colon carcinoma cells have not been reported. To investigate the chemopreventive effects of gamma-tocotrienol on colon cancer, we examined ...

Mollaret meningitis (MM) occurs mainly in females and is characterized by recurrent episodes of headache, transient neurological abnormalities, and the cerebrospinal fluid containing mononuclear cells. HSV-2 was usually identified as the causative agent. Recently, we found that recurrent headaches in non-HIV-infected subjects were due to acquired cerebral toxoplasmosis (CT). The ...

Cytokines are small secreted molecules, which mediate cross-talk between cells involved in the immune response. Interferons (IFN)s, constitute a class of cytokines with antiviral activities, and the type I IFNs have been ascribed particularly important roles in the innate antiviral response. Type III IFNs (also known as IFN-lambda or interleukin ...

The microsporidian Encephalitozoon intestinalis develops within intestinal epithelial cells (enterocytes) and is an important opportunistic diarrhoeal pathogen associated with AIDS. Little is known about the protective immune response against the parasite although in mice IFN-gamma is involved and is required to prevent dissemination of the infection to other organs. The ...

Immunization with vaccinia virus causes long-term immunity. Efforts have been made to characterize the T cells responsible for this protection. Recently, T cell subsets were described that not only co-express multiple cytokines, but also show increased per cell cytokine productivity. These highly productive cells are often considered to be the ...

Mobile phones are widely used globally. However, the biological effects due to exposure to electromagnetic fields (EMF) produced by mobile phones are largely unknown. Environmental and occupational exposure of humans to gamma-rays is a biologically relevant phenomenon. Consequently studies were undertaken to examine the interactions between gamma-rays and EMF on ...

To date, the most effective cure for metastatic melanoma remains the surgical resection of the primary tumor. Recently, tocotrienol-rich-fraction has shown antiproliferative effect on cancer cells. To elucidate this anticancer property in malignant melanoma, this study aimed, first, to identify the most potent isomer for eliminating melanoma cells and second ...

INTRODUCTION: Interleukin (IL)-17 plays an important role in the pathogenesis of rheumatoid arthritis and the mouse model collagen-induced arthritis (CIA). Interferon(IFN)-gamma and IL-4 have been shown to suppress Th17 development in vitro, but their potential immunoregulatory roles in vivo are uncertain. The goals of this study were to determine the ...

Azithromycin (AZM), a 15-member macrolide antibiotic, possesses anti-inflammatory activity. Macrophages are important in innate and acquired immunity, and produce pro-inflammatory cytokines such as interleukin (IL)-12, which are composed of subunit p40 and p35. The key function of IL-12 is the induction and maintenance of T-helper-1 responses, which is associated with ...

Although reovirus has been used in tests as a potential cancer therapeutic agent against a variety of cancer cells, its application to hepatocellular carcinoma cells, in which the hepatitis B virus (HBV) X (HBX) protein of HBV plays a primary role, has not yet been explored. Here, we describe experiments ...

We describe a novel basic leucine zipper containing type I IFN-inducible early response gene SARI (Suppressor of AP-1, Regulated by IFN). Steady-state SARI mRNA expression was detected in multiple lineage-specific normal cells, but not in their transformed/tumorigenic counterparts. In normal and cancer cells, SARI expression was induced 2 h after ...

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A conundrum of innate antiviral immunity is how nucleic acid-sensing Toll-like receptors (TLRs) and RIG-I/MDA5 receptors cooperate during virus infection. The conventional wisdom has been that the activation of these receptor pathways evokes type I IFN (IFN) responses. Here, we provide evidence for a critical role of a Toll-like receptor ...

A vaccine for human immunodeficiency virus (HIV) infection is desperately needed to control the AIDS pandemic. To address this problem, we constructed single-cycle simian immunodeficiency viruses (SIVs) pseudotyped with the glycoprotein of vesicular stomatitis virus and expressing different levels of gamma interferon (IFN-gamma) as a potential vaccine strategy. We previously ...

BACKGROUND: Elucidating the cellular and molecular basis of naturally acquired immunity to Plasmodium falciparum infection would assist in developing a rationally based malaria vaccine. Innate, intermediate, and adaptive immune mechanisms are all likely to contribute to immunity. Interferon-gamma (IFN-gamma) has been implicated in both protection against and the pathogenesis of ...

OBJECTIVE: Two types of interferons (IFNs), type I (IFN-alpha/beta) and type III (IFN-lambdas), utilize distinct receptor complexes to induce similar signalling and biological activities, including recently demonstrated for IFN-lambdas antitumour activity. However, ability of type III IFNs to regulate cell population growth remains largely uncharacterized. MATERIALS AND METHODS: Intact and ...

Activated macrophages and their inflammatory products play a key role in innate immunity and in pathogenesis of autoimmune/inflammatory diseases. Macrophage activation needs to be tightly regulated to rapidly mount responses to infectious challenges but to avoid toxicity associated with excessive activation. Rapid and potent macrophage activation is driven by cytokine-mediated ...

Cellular senescence is a stress-response phenomenon in which cells lose the ability to proliferate; it is induced by telomere shortening, activation of oncogenes or tumor suppressor genes, or exposure to a sub-lethal dose of DNA damaging agents or oxidative stresses. cDNA microarray analysis reveals that the levels of interferons (IFNs) ...

Many studies indicated that the CD40/CD40 ligand (CD40L) pathway plays an important role in the pathogenesis of atherosclerosis. It has been demonstrated a protective role of dehydroepiandrosterone (DHEA) against atherosclerosis. The major purpose of our present work was to assess whether DHEA could decrease the expression of CD40 and CD40L ...

Tpl2 (Tumor progression locus 2), also known as Cot/MAP3K8, is a hematopoietically expressed serine-threonine kinase. Tpl2 is known to have critical functions in innate immunity in regulating tumor necrosis factor-alpha, Toll-like receptor, and G protein-coupled receptor signaling; however, our understanding of its physiological role in T cells is limited. We ...

Upon viral infection, the major defense mounted by the host immune system is activation of the interferon (IFN)-mediated antiviral pathway, which is mediated by IFN regulatory factors (IRFs). In order to complete their life cycle, viruses must modulate host IFN-mediated immune responses. Despite its association with significant human health problems, ...

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by early onset of recurrent and severe infections. The molecular defects causing CGD are heterogeneous and lead to absence, low expression, or malfunctioning of one of the phagocyte NADPH oxidase components. It is known that mutations leading to CGD reside within ...

The dsRNA-dependent protein kinase, PKR, is a central component in antiviral defense. The biological importance of PKR is further remarked by its critical role in apoptosis induced by a variety of stresses. Here, we analyzed the implication of oxidative stress in the induction of PKR-dependent apoptosis in Jurkat cells. Our ...

Interferon-gamma (IFN-gamma) serves numerous functions in the regulation of the immune response. During the early phase of the immune response IFN-gamma is produced by natural killer and natural killer T cells. Although the effects of this cytokine on antigen presenting cells and other cell types are known, its direct role ...

Matrix metalloproteinases (MMPs) are induced during inflammatory responses and are important for immune regulation, angiogenesis, wound healing, and tissue remodeling. Expression of MMPs needs to be tightly controlled to avoid excessive tissue damage. In this study, we investigated the regulation of MMP expression by inflammatory factors in primary human monocytes ...

Recombinant pestivirus envelope glycoprotein E(rns) has been shown to interfere with dsRNA-induced interferon (IFN-alpha/beta) synthesis. This study demonstrated that authentic, enzymically active E(rns) produced in mammalian cells prevented a dsRNA-induced IFN response when present in the supernatant of bovine cells. Strikingly, IFN synthesis of cells expressing E(rns) was eliminated after ...

Arenaviruses such as Lassa virus cause a spectrum of disease in humans ranging from mild febrile illness to lethal haemorrhagic fever. The contributions of innate immunity to protection or pathogenicity are unknown. We compared patterns of expression of cytokines of innate immunity in mild versus severe arenavirus disease using an ...

Accumulating evidence suggests that nitric oxide (NO) and prostaglandin E(2) (PGE(2)) are involved in the pathogenesis of various chronic inflammatory diseases and cancer. During the course of a screening program to identify natural anti-inflammatory substances, we isolated the compound 2-amino-3H-phenoxazin-3-one (APO) from an extract of the edible brown mushroom Agaricus ...

Cytomegalovirus (CMV) is the leading transmittable cause of congenital brain abnormalities in children and infection results in fatal ventriculoencephalitis in advanced acquired immunodeficiency syndrome (AIDS) patients. Pathology associated with CMV brain infection is seen predominantly in the periventricular region, an area known to harbor neural stem cells (NSCs). In the ...

Interferon regulatory factors (IRF) 3 and 7 in mammals are known to be crucial in regulating the type I interferon (IFN) response to viral infection as part of transcriptional complexes binding to IRF-binding elements (IRF-Es) and interferon stimulatory response elements (ISREs) within IFN and interferon-stimulated genes (ISGs). Here we report ...

Cellular immune responses against Eimeria bovis are highly specific and a key factor for the development of protection against challenge infections. In this study we investigate the cellular immune responses of E. bovis primary and challenge infected calves stimulated in vitro by E. bovis merozoite I-antigen. Primary infection was accompanied ...

A large body of evidence suggests that immune system dysregulation is associated with Major Depressive Disorder (MDD) in adults. This study extends this work to adolescent MDD to examine the hypotheses of immune system dysregulation in adolescents with MDD, as manifested by significantly: (i) elevated plasma levels of cytokines (interferon ...

It has been suggested that tumour cell lysis by gamma-radiation induces a tumoral antigen release eliciting an immune response. It is not clear how a specific immune response in cervical cancer patients is developed after radiotherapy. This study is an attempt to investigate the role of the human papillomavirus type ...

Astrocytes play a number of important physiological roles in CNS homeostasis. Inflammation stimulates astrocytes to secrete cytokines and chemokines that guide macrophages/microglia and T cells to sites of injury/inflammation. Herein, we describe how these processes are controlled by the suppressor of cytokine signaling (SOCS) proteins, a family of proteins that ...

INTRODUCTION: Immune system dysregulation has been demonstrated to occur during and immediately following spaceflight. If found to persist during lengthy flights, this phenomenon could be a serious health risk to crewmembers participating in lunar or Mars missions. METHODS: A comprehensive postflight immune assessment was performed on 17 short-duration Space Shuttle ...

In this study we examined the ability of interferon-gamma (IFN-gamma) to regulate mammary epithelial cell growth and gene expression, with particular emphasis on two genes: Maspin (a member of serine protease inhibitor superfamily), and the lysosomal aspartyl endopeptidase cathepsin D (CatD). The protein products of these genes are critically involved ...

Interferon (IFN)-gamma was originally characterized as a pro-inflammatory cytokine with T helper type 1-inducing activity, but subsequent work has demonstrated that mice deficient in IFN-gamma or IFN-gamma receptor show exacerbated inflammatory responses and accelerated allograft rejection, suggesting that IFN-gamma also has important immunoregulatory functions. Here, we demonstrate that ex vivo ...

The shift to the production of a Th1 cytokine profile during an intracellular infection has been shown to depend on antigen presenting cells-derived IL-12 and T-cell-derived IFN-gamma production. IL-18 facilitates Th1 priming in synergy with IL-12 through the stimulation of IFN-gamma production by T cells, B cells, NK cells, macrophages ...

Osteopontin (Opn), an important mediator of the cell-mediated immune response, enhances the host immune response against mycobacterial infections. Infections caused by Mycobacterium avium ssp. paratuberculosis (MAP) have a devastating effect on the dairy industry. We sought to characterize Opn at the level of gene and protein expression in periparturient dairy ...

We studied in vitro production of interferon-gamma and expression of interferon-gamma receptors (R1 and R2) by the peripheral blood mononuclear cells of 24 HIV-1-infected patients and 12 healthy volunteers. Interferon-gamma production was lower in HIV-1-infected patients compared with healthy volunteers (p < 0.05), and it further declined in patients with ...

Berbamine (BM) is an herbal compound derived from Berberis vulgaris L commonly used in traditional Chinese medicine. In this study, we show that BM has potent anti-inflammatory properties through novel regulatory mechanisms, leading to reduced encephalitogenic T cell responses and amelioration of experimental autoimmune encephalomyelitis (EAE). The treatment effect of ...

Activation of type 1 immunity plays a critical role in host defense mechanisms against infectious disease and tumor. Lactic acid bacteria, existing in the gastrointestinal tract, are one of the powerful tools to induce a type-1-dominant immunity, which may improve Th2-dependent allergic diseases. In the present work, we found that ...

Natural killer (NK) cells play an important role in the innate immune response. Interleukin-18 (IL-18) is a well-known interferon-gamma (IFN-gamma inducing factor, which stimulates immune response in NK and T cells. Sphingosine kinase (SPHK) catalyzes the formation of sphingosine 1-phosphate (S1P), which acts as a second messenger to function as ...