Articles That Use the Tag Name:

proinflammatory cytokine


Interplay Between microRNAs, Toll-like Receptors, and HIV-1: Potential Implications in HIV-1 Replication and Chronic Immune Activation

Abstract: MicroRNAs (miRNAs) are important cellular, small non-coding RNAs that regulate host gene expression and have well-characterized roles in inflammation and infectious diseases. It has become apparent as well that cellular miRNAs can play crucial roles in controlling HIV-1 infection and replication. Whether HIV-1 encodes and is able to express viral miRNAs in infected cells remains controversial. HIV-1 can manipulate the biogenesis of miRNAs as well as the expression profiles of cellular miRNAs. Toll-Like receptors (TLRs) are important pathogen recognition receptors that sense invading pathogens orchestrating innate and adaptive immune responses. Innate immune recognition of HIV-1 infection leads to activation of TLR7/8. Recent evidence has shown that certain miRNAs can also be recognized by TLR7/8 leading to immune activation. However, the potential TLR7/8-mediated recognition of HIV-1 encoded miRNAs and/or cellular miRNAs modulated in HIV-1 infected cells has not been experimentally explored. In this review, we summarize the current literature on HIV-1 infection and miRNAs. Furthermore, we underscore the need for future research on potential miRNA-induced activation of TLR7/8, which might contribute to the chronic immune activation observed in HIV-1 infected patients. ... Read more

Novel Therapeutic Approaches for Celiac Disease

Abstract: Celiac disease (CD), which mainly affects the small intestine, is the only systemic autoimmune disorder with an identified environmental trigger which is dietary gluten. Lifelong adherence to a strict gluten free diet (GFD) is currently the only accepted treatment. CD is increasingly diagnosed and the GFD is known to be associated with a large treatment burden. Furthermore, a substantial number of CD patients show an incomplete clinical response to the GFD. These factors have led to demands for the development and testing of novel, non-dietary, therapeutic agents that are both safe and effective. CD pathogenesis is well elucidated which has greatly aided targeted drug development. Compounds currently being tested in phase II clinical trials include glutenase enzymes (to detoxify gluten) and a tight junction modulator (to reduce access of gluten peptides to lamina propria antigen presenting cells). Other promising approaches include inhibition of the transglutaminase 2 enzyme, blocking antigen presentation by HLA-DQ2 or HLA-DQ8, induction of tolerance, and modulation of the inflammatory response. It is hoped that non-dietary therapy for CD will become available in the coming years and can both reduce the burden of treatment of CD and help patients whose symptoms do not respond completely to the GFD. ... Read more

Advances in Mechanisms of Systemic Lupus Erythematosus

Abstract: Systemic lupus erythematosus (SLE) is a complex autoimmune disease associated with hormonal, environmental, and genetic factors and linked to the tolerance breakdown of B and T cells to self-antigens. SLE is characterized by the presence in patient serum of autoantibodies raised against nuclear components. Association of these antibodies to self-antigens, complement factors, DNA, and particular proteins will form circulating immune complexes (CIC) which can deposit in several organs, causing tissue damage and clinical manifestations. Historically, SLE is considered as an adaptive immune system disorder. Over the past decade, advances in the understanding of SLE pathogenesis placed the innate immune system as a key player in perpetuating and amplifying this systemic disease. In this review, we summarize some recent key advances in understanding the SLE immune-pathogenesis with a particular focus on newly discovered key factors from the innate immune system and how they influence the pathogenic adaptive immune system: neutrophils and neutrophil extracellular traps (NETs), plasmacytoid dendritic cells (pDCs) and type I interferons, basophils and autoreactive IgE, monocytes/macrophages and the inflammasome. Recent advances on B and T cell involvement in the SLE pathogenesis mechanisms are also discussed. Although the disease is clinically, genetically, and immunologically heterogeneous between affected individuals, the latest discoveries are offering new promising therapeutic strategies. ... Read more

Treating IgA Nephropathy: Quid Novi?

Abstract: IgA nephropathy is a common autoimmune renal disease resulting in kidney failure for patients with significant proteinuria. The therapeutic options are limited including non-specific treatment to reduce proteinuria accomplished by renin-angiotensin blockade. Strategies to control intrarenal inflammation include the administration of fish oil and for severe disease the use of immunosuppressive agents such as cyclophosphamide, glucocorticosteroids, and mycophenolate mofetil. In light of the limited option, there is an unmet need for novel therapeutic intervention in patients with progressive disease. Herein, we review the evidence for existing treatment choices and explore new immunopharmacologic agents being investigated for IgA nephropathy. ... Read more

Novel Insight into the Role of Alpha-actinin-1 in Rheumatoid Arthritis

Abstract: The knowledge of rheumatoid arthritis (RA) pathology is rapidly advancing and becoming more and more complex, and a simple fact is that the major organ targeted by RA pathogenic factors is the synovium. It is well known that fibroblast-like synovial (FLS) cell is the major cell-type for constructing synovium. Following stimulation by pro-inflammatory cytokines, FLS cells are phenotypically changed to have the capability to proliferate abnormally. Recently we demonstrated that α-actinin-1 (ACTN1) gene is significantly increased in synovial tissues obtained from RA, as compared to osteoarthritis (OA). We therefore reviewed the literature about α-actinins (ACTNs) and we now propose that ACTN1 may function as a "terminal effector" of intracellular signalings initiated by tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) in RA. Future research on ACTN1 may help to improve the current therapeutic and diagnostic strategies of RA. ... Read more

Combination of Virotherapy and T-cell Therapy: Arming Oncolytic Virus with T-cell Engagers

Abstract: While cure rates for several cancers have significantly improved, the outcome for patients with advanced solid tumors remains grimly unchanged over the last decades. Thus, there is a need for new therapies that could improve outcome for patients who fail current therapies. Oncolytic (cancer destroying) vaccinia virus (VV) would be an appealing addition to the current therapies of cancers because of its ability to infect, replicate in, and lyse tumor cells, and spread to other tumor cells in successive rounds of replication. While clinical studies have demonstrated their safety, the antitumor efficacy of oncolytic VVs has been suboptimal. Oncolytic VVs' major mode of action is the destruction of tumor cells, which can subsequently activate a component of the immune system called T-cells that can travel to distant sites and target against any tumor they find. At present, virus spread through tumors, as well as the activation of tumor-specific T-cells, is limited, explaining the observed suboptimal antitumor activity of current oncolytic VVs. Thus it would be desirable to make the oncolytic VVs more powerful stimulators of immunity through activating resident T-cells within the tumors so that they will kill tumor cells and stop new tumors from growing. To activate T-cells within tumors, a new molecule called a T-cell engager that couples the T cell and the tumor cell, which increases the effectiveness of the T cells and their activation, has been constructed. This review summarizes the progress of the emerging field of combinations of oncolytic virotherapy and T-cell based therapy. ... Read more

Scleritis: Challenges in Immunopathogenesis and Treatment

Abstract: Scleritis is an uncommon disease characterized by inflammation of the sclera and adjacent ocular structures. Recent studies have led to significant progress in understanding the epidemiology, immunopathogenesis, severity assessment, treatment, and prognosis of this potentially sight threatening disease. Despite these advances, significant challenges remain regarding our understanding of the mechanisms of scleral destruction and inflammation, and the rational approach to treatment. Information from studies in associated systemic diseases and vasculitis and a small number of studies of ocular tissue has revealed the prominent role of T and B cells, autoantibodies, immune complexes, and cytokines, such as TNF-alpha. These studies have prompted clinical trials that have demonstrated the effectiveness of anti-TNF, anti-B cell therapy, systemic immunosuppression, and more recently the use of local sub-conjunctival steroid treatment. ... Read more

Adipokines: Novel Players in Rheumatic Diseases

Abstract: A large body of evidence from clinical and experimental studies is aiding to understand the close relationships between obesity and rheumatic diseases. For instance, it is generally accepted that obesity contributes to the development of osteoarthritis by increasing mechanical load of the joints, at least in weight bearing joints. However, besides mechanical effects, recent studies demonstrated that white adipose tissue is able to secrete a plethora of soluble factors, called adipokines, which have a critical role in the development and progression of some rheumatic diseases such as osteoarthritis and rheumatoid arthritis. In this article, we summarize the recent findings on the interaction of certain adipokines with the two most common rheumatic diseases: osteoarthritis and rheumatoid arthritis. ... Read more

Relevance of the Type I Interferon Signature in Multiple Sclerosis Towards a Personalized Medicine Approach for Interferon-beta Therapy

Abstract: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system. The disease is characterized by progressive neurological dysfunction due to demyelination of the nerves, which leads to disability. Currently, no curative therapy is available and patients are subjected to a prolonged course of treatment. Interferon-β (IFNβ) was the first agent to show clinical efficacy in the treatment of MS, and is still the best available therapy. Unfortunately, clinical experience indicates that approximately 40% of the patients do not or only poorly respond to IFNβ treatment. Recent advances revealed the presence of an activated type I IFN pathway in a subset of treatment naïve patients with relapsing remitting MS (RRMS), as shown by the presence of an "IFN signature" and type I IFN bioactivity in the blood of these patients. Evidence exists that quantification of the IFN signature in RRMS is informative as a biomarker to predict the clinical response to IFNβ. In this review we summarize the current evidence of type I IFN activation in RRMS and its clinical relevance. ... Read more

Elusive Alzheimer's Disease: Can Immune Signatures Help Our Understanding of This Challenging Disease? Part 2: New Immune Paradigm

Abstract: Alzheimer's disease (AD) is the most common form of dementia. Its most important pathological hallmarks are profound neuronal loss, presence of intracellular neurofibrillary tangles, and extracellular deposition of beta-amyloid protein (Aβ) as beta-amyloid plaques. One of the most important risk factors for AD is age and with the increase of life-expectancy AD has become the most common form of dementia. The current "Holy Grail" is to be able to diagnose variants of AD before they manifest clinically and before irreparable brain damage is done. To be able to do so, we need robust and reliable biomarkers which reflect the pathogenesis of AD. This is essential because such biomarkers might indicate pathways that could be targeted for interventions aiming at disease prevention or amelioration. Although much attention has been focused on Aβ in this respect, it may not be as attractive a target as thought if current doubts concerning its causative role are substantiated. This review will be in two parts, the first part dealt with the current clinical knowledge and the questions raised by the Aβ cascade hypothesis in the pathogenesis of AD and this second part aims to synthesize our current knowledge and new data suggesting how immunity may contribute to the development of AD and may itself be targeted in future treatments. ... Read more

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