Interferon-γ increases neuronal death in response to amyloid-β1-42

Background  

Alzheimer's disease is a neurodegenerative disorder characterized by a progressive cognitive impairment, the consequence of neuronal dysfunction and ultimately the death of neurons. The amyloid hypothesis proposes that neuronal damage results from the accumulation of insoluble, hydrophobic, fibrillar peptides such as amyloid-β_1-42. These peptides activate enzymes resulting in a cascade of second messengers including prostaglandins and platelet-activating factor. Apoptosis of neurons is thought to follow as a consequence of the uncontrolled release of second messengers. Biochemical, histopathological and genetic studies suggest that pro-inflammatory cytokines play a role in neurodegeneration during Alzheimer's disease. In the current study we examined the effects of interferon (IFN)-γ, tumour necrosis factor (TNF)α, interleukin (IL)-1β and IL-6 on neurons.     

A 12-week regimen of caloric restriction improves levels of adipokines and pro-inflammatory cytokines in Korean women with BMIs greater than 23 kg/m2

Introduction  

Adipose tissue mass (ATM) is an important source of adipokines. Increases in ATM contribute to chronic low-grade inflammation characterized by high levels of pro-inflammatory cytokines. We investigated the effects of body fat reduction on blood levels of adipokines and pro-inflammatory cytokines in Korean women with BMIs >23 kg/m².     

Mast cells participate in allograft rejection: can IL-37 play an inhibitory role?

Objective

The aim of this study was to evaluate the role of mast cells (MCs) in allograft rejection, eventually inhibited by IL-37. Immune cells including MCs participate in allograft rejection by generating IL-1, IL-33, TNF and other cytokines.

Methods

We evaluated allograft rejection on the experience of our experimental data and using the relevant literature.

Results

MCs are involved in initiation and regulation of innate and adaptive immune responses-pathways. MCs are important pro-inflammatory cells which express high-affinity receptor FceRI and can be activated by IgE and some pro-inflammatory cytokines, such as IL-1 and IL-33. The cross-linkage of high affinity IgE receptor on MCs by antigen ligation has a crucial role in allergy, asthma, anaphylaxis, cancer and allograft rejection. MCs mediate immunity in organ transplant, leading to the activation of allospecific T cells implicated in the rejection and generate pro-inflammatory cytokines/chemokines. IL-1 pro-inflammatory cytokine family members released by MCs mediate allograft rejection and inflammation. IL-37 is also an IL-1 family member generated by macrophage cell line in small amounts, which binds to IL-18Rα and produces an anti-inflammatory effect. IL-37 provokes the inhibition of TLR signaling, TLR-induced mTOR and (MyD88)-mediated responses, suppressing pro-inflammatory IL-1 family members and increasing IL-10.

Conclusion

IL-37 inhibition offers the opportunity to immunologically modulate MCs, by suppressing their production of IL-1 family members and reducing the risk of allograft rejection, resulting as a potential good therapeutic new cytokine. Here, we report the relationship between inflammatory MCs, allograft rejection and pro-inflammatory and anti-inflammatory IL-37.

     

ITAM Receptor Signaling and the NLRP3 Inflammasome in Antifungal Immunity

Introduction  

Infections with fungi can cause systemic life-threatening diseases in immunocompromised individuals like cancer or AIDS patients. Recent work has uncovered essential roles for C-type lectin pattern recognition receptors, spleen tyrosine kinase (SYK) and the cytosolic NLRP3 inflammasome in innate antifungal immunity. Upon fungal infection, SYK is activated by several ITAM-containing or ITAM-coupled C-type lectin receptors on myeloid cells leading to the production of pro-inflammatory cytokines including IL-1β to initiate antifungal responses. Mature IL-1β production requires in addition to the synthesis of pro-IL-1β a cleavage of the precursor protein by the inflammatory Caspase-1 which is controlled within the NLRP3 inflammasome.     

Counteracting neuroinflammation in experimental Parkinson’s disease favors recovery of function: effects of Er-NPCs administration

Background

Parkinson’s disease (PD) is the second most common neurodegenerative disease, presenting with midbrain dopaminergic neurons degeneration. A number of studies suggest that microglial activation may have a role in PD. It has emerged that inflammation-derived oxidative stress and cytokine-dependent toxicity may contribute to nigrostriatal pathway degeneration and exacerbate the progression of the disease in patients with idiopathic PD. Cell therapies have long been considered a feasible regenerative approach to compensate for the loss of specific cell populations such as the one that occurs in PD. We recently demonstrated that erythropoietin-releasing neural precursors cells (Er-NPCs) administered to MPTP-intoxicated animals survive after transplantation in the recipient’s damaged brain, differentiate, and rescue degenerating striatal dopaminergic neurons. Here, we aimed to investigate the potential anti-inflammatory actions of Er-NPCs infused in an MPTP experimental model of PD.

Methods

The degeneration of dopaminergic neurons was caused by MPTP administration in C57BL/6 male mice. 2.5?×?10⁵ GFP-labeled Er-NPCs were administered by stereotaxic injection unilaterally in the left striatum. Functional recovery was assessed by two independent behavioral tests. Neuroinflammation was investigated measuring the mRNAs levels of pro-inflammatory and anti-inflammatory cytokines, and immunohistochemistry studies were performed to evaluate markers of inflammation and the potential rescue of tyrosine hydroxylase (TH) projections in the striatum of recipient mice.

Results

Er-NPC administration promoted a rapid anti-inflammatory effect that was already evident 24?h after transplant with a decrease of pro-inflammatory and increase of anti-inflammatory cytokines mRNA expression levels. This effect was maintained until the end of the observational period, 2?weeks post-transplant. Here, we show that Er-NPCs transplant reduces macrophage infiltration, directly counteracting the M1-like pro-inflammatory response of murine-activated microglia, which corresponds to the decrease of CD68 and CD86 markers, and induces M2-like pro-regeneration traits, as indicated by the increase of CD206 and IL-10 expression. Moreover, we also show that this activity is mediated by Er-NPCs-derived erythropoietin (EPO) since the co-injection of cells with anti-EPO antibodies neutralizes the anti-inflammatory effect of the Er-NPCs treatment.

Conclusion

This study shows the anti-inflammatory actions exerted by Er-NPCs, and we suggest that these cells may represent good candidates for cellular therapy to counteract neuroinflammation in neurodegenerative disorders.

     

5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) attenuates the expression of LPS- and Aβ peptide-induced inflammatory mediators in astroglia

Background  

Alzheimer's disease (AD) pathology shows characteristic 'plaques' rich in amyloid beta (Aβ) peptide deposits. Inflammatory process-related proteins such as pro-inflammatory cytokines have been detected in AD brain suggesting that an inflammatory immune reaction also plays a role in the pathogenesis of AD. Glial cells in culture respond to LPS and Aβ stimuli by upregulating the expression of cytokines TNF-α, IL-1β, and IL-6, and also the expression of proinflammatory genes iNOS and COX-2. We have earlier reported that LPS/Aβ stimulation-induced ceramide and ROS generation leads to iNOS expression and nitric oxide production in glial cells. The present study was undertaken to investigate the neuroprotective function of AICAR (a potent activator of AMP-activated protein kinase) in blocking the pro-oxidant/proinflammatory responses induced in primary glial cultures treated with LPS and Aβ peptide.     

Induction of cell cycle changes and modulation of apoptogenic/anti-apoptotic and extracellular signaling regulatory protein expression by water extracts of I'm-Yunity™ (PSP)

Background  

Inflammation is a predominant characteristic of autoimmune diseases which is characterized by the increased expression of pro-inflammatory cytokines. Soon to be published work from our laboratory has shown that ingestion of Perna canaliculus prevents the development of autoimmune diseases such as Systemic Lupus Erythematosus and rheumatoid arthritis in laboratory animals. The current paper attempts to illustrate how Perna can alleviate inflammation by modulating inflammatory cytokines, cyclooxygenase enzymes and Immunoglobulin-G (IgG) levels.     

sHLA-I Contamination,A Novel Mechanism to Explain Ex Vivo/In Vitro Modulation of IL-10 Synthesis and Release in CD8<Superscript>+</Superscript> T Lymphocytes and in Neutrophils Following Intravenous Immunoglobulin Infusion

Background  

Numerous mechanisms have been proposed to explain the beneficial action of intravenous immune globulin (IVIG) in autoimmune and systemic inflammatory disorders; among others, they could decrease pro-inflammatory cytokine levels and also induce anti-inflammatory cytokines.     

Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD

Background  

Microglia are associated with neuritic plaques in Alzheimer disease (AD) and serve as a primary component of the innate immune response in the brain. Neuritic plaques are fibrous deposits composed of the amyloid beta-peptide fragments (Abeta) of the amyloid precursor protein (APP). Numerous studies have shown that the immune cells in the vicinity of amyloid deposits in AD express mRNA and proteins for pro-inflammatory cytokines, leading to the hypothesis that microglia demonstrate classical (Th-1) immune activation in AD. Nonetheless, the complex role of microglial activation has yet to be fully explored since recent studies show that peripheral macrophages enter an "alternative" activation state.     

Cloning and characterization of deer mouse (Peromyscus maniculatus) cytokine and chemokine cDNAs

Background  

Sin Nombre virus (SNV) establishes a persistent infection in the deer mouse, Peromyscus maniculatus. A strong antibody response occurs in response to SNV infection, but the role of the innate immune response is unclear. To address this issue, we have initiated an effort to identify and characterize deer mouse cytokine and chemokine genes. Such cytokines and chemokines are involved in various aspects of immunity, including the transition from innate to adaptive responses, type I and type II responses, recruitment of leukocytes to sites of infection, and production of mature cells from bone marrow progenitors.     

Toll-like receptor 2 signaling is a mediator of apoptosis in herpes simplex virus-infected microglia

Background  

Information regarding the response of brain cells to infection with herpes simplex virus (HSV)-1 is needed for a complete understanding of viral neuropathogenesis. We have recently demonstrated that microglial cells respond to HSV infection by producing a number of proinflammatory cytokines and chemokines through a mechanism involving Toll-like receptor 2 (TLR2). Following this cytokine burst, microglial cells rapidly undergo cell death by apoptosis. We hypothesized that TLR2 signaling might mediate the cell death process as well.     

Relevancia de TLR4 en la infección por virus de la hepatitis C

Objective

The presence of the Asp-299Gly and Thr-399Ile polymorphisms in the toll-like receptor 4 (TLR4) gene was studied in subjects with HCV infection and HCV+HIV coinfection. The expression and function of TLR4 as regards these polymorphisms is assessed.

Material and methods

The study included 53 patients infected with HCV, among whom 27 had coinfection HCV+HIV, and 30 healthy subjects. The polymorphisms were studied by PCR-RFLP. The number of lymphocyte subsets, as well as TLR4 expression, was determined by flow cytometry, and the concentration of cytokines was measured in serum by (cytometric bead assay) CBA.

Results

CD4⁺ T cells were significantly decreased in patients coinfected with HCV+HIV. There was no association between the presence of any of the two studied polymorphisms and the susceptibility to suffer from infection. TLR4 was less expressed in B cells, whereas it was increased in T cells and, in particular, monocytes. A significant increase in the levels of circulating pro-inflammatory cytokines was found, being two-fold increased in coinfected subjects as compared with patients with isolated HCV infection. None of the findings in cell subsets, TLR4 expression and cytokines was associated with the studied TLR4 polymorphism.

Discussion

The expression of TLR4 in T cells and monocytes is increased in HCV infection and is accompanied by increased serum levels of proinflammatory cytokines. These findings do not have any relationship with the Asp-299Gly and Thr-399Ile polymorphisms.     

Soybean-derived Bowman-Birk inhibitor inhibits neurotoxicity of LPS-activated macrophages

Background  

Lipopolysaccharide (LPS), the major component of the outer membrane of gram-negative bacteria, can activate immune cells including macrophages. Activation of macrophages in the central nervous system (CNS) contributes to neuronal injury. Bowman-Birk inhibitor (BBI), a soybean-derived protease inhibitor, has anti-inflammatory properties. In this study, we examined whether BBI has the ability to inhibit LPS-mediated macrophage activation, reducing the release of pro-inflammatory cytokines and subsequent neurotoxicity in primary cortical neural cultures.     

Natural-Killer Cell-Derived Cytolytic Molecules in HIV-Associated Pulmonary Tuberculosis—Role of Exogenous Interleukins

Objective  

The ability of NK cells to produce cytolytic molecules is impaired during HIV infection. The objective of the present study is to investigate whether impairment in production of innate cytokines in HIV-infected individuals is responsible for the defective NK cytolytic response.     

Absence of IFNγ expression induces neuronal degeneration in the spinal cord of adult mice

Background  

Interferon gamma (IFNγ) is a pro-inflammatory cytokine, which may be up-regulated after trauma to the peripheral or central nervous system. Such changes include reactive gliosis and synaptic plasticity that are considered important responses to the proper regenerative response after injury. Also, IFNγ is involved in the upregulation of the major histocompatibility complex class I (MHC class I), which has recently been shown to play an important role in the synaptic plasticity process following axotomy. There is also evidence that IFNγ may interfere in the differentiation and survival of neuronal cells. However, little is known about the effects of IFNγ absence on spinal cord neurons after injury.     

Reactive oxygen species and p47phox activation are essential for the Mycobacterium tuberculosis-induced pro-inflammatory response in murine microglia

Background  

Activated microglia elicits a robust amount of pro-inflammatory cytokines, which are implicated in the pathogenesis of tuberculosis in the central nervous system (CNS). However, little is known about the intracellular signaling mechanisms governing these inflammatory responses in microglia in response to Mycobacterium tuberculosis (Mtb).     

CPAF,HSP60 and MOMP antigens elicit pro-inflammatory cytokines production in the peripheral blood mononuclear cells from genital Chlamydia trachomatis-infected patients

Background

Persistent inflammation caused by Chlamydia trachomatis in the female genital compartment represents one of the major causes of pelvic inflammatory disease (PID), ectopic pregnancy and infertility in females. Here, we examined the pro-inflammatory cytokine response following stimulation with three different types of C. trachomatis antigens, viz. chlamydial protease-like factor (CPAF), heat shock protein 60 (HSP60) and major outer membrane protein (MOMP).

Polybacterial challenge effects on cytokine/chemokine production by macrophages and dendritic cells

Objective  

To investigate the polymicrobial infection of periodontal disease, which elicits inflammatory mediators/cytokines/chemokines in the local gingival tissues, and a polybacterial challenge of antigen-presenting cells, e.g. macrophages and dendritic cells (DCs), at the mucosal surface.