Pharmacogenomics of interferon-β in multiple sclerosis: What has been accomplished and how can we ensure future progress?
Multiple sclerosis (MS) is a chronic inflammatory disease that involves the demyelination of axons in the central nervous system (CNS). It is unclear what triggers the development of MS, although its pathogenesis has been linked to an abnormal immune cell response toward myelin and oligodendrocytes. It is believed that Th1 T-helper cells permeate the blood-brain barrier, where they activate cytokines that recruit other immune cells that in turn contribute to axonal damage [34]. These mechanisms may result in an increased number and volume of brain lesions on magnetic resonance imaging (MRI), which correlate to some degree ...
Source: Cytokine and Growth Factor Reviews - October 31, 2014 Category: Molecular Biology Authors: Rebecca J. Carlson, J. Ronald Doucette, Katherine Knox, Adil J. Nazarali Tags: Survey Source Type: research
Role of type I interferon in inducing a protective immune response: perspectives for clinical applications
Type I IFN (IFN-I) are pleiotropic cytokines originally identified for their antiviral activity. However, during almost sixty years of IFN research these cytokines have represented a “moving target” [1], since a variety of other biological effects, different from the antiviral activity, have been progressively described, including antitumor effects [2] and different types of activities on cells of the immune system [3,4]. Notably, IFN-α are the IFN-I subtypes which have shown the longest record of clinical use. (Source: Cytokine and Growth Factor Reviews)
Source: Cytokine and Growth Factor Reviews - October 30, 2014 Category: Molecular Biology Authors: Paola Rizza, Franca Moretti, Imerio Capone, Filippo Belardelli Tags: Mini review Source Type: research
Mislocalization of the interferon inducible protein IFI16 by environmental insults: implications in autoimmunity
The IFI16 protein was discovered two decades ago as a protein constitutively expressed in the nucleus and nucleoli of lymphoid cells that can be induced by Interferons in myeloid cells [1–3]. Such interferon-induced expression of IFI16 is transcriptionally controlled by AP-1 [4]. It is naturally present in 3 isoforms (A, B and C) that arise due to differential mRNA splicing; of which, the 729 amino acid IFI16-B isoform is most abundant [5]. While previously IFI16 expression was considered to be limited to hematopoietic cells, later it was discovered also in vascular endothelial cells and keratinocytes [6]. (Source: Cytok...
Source: Cytokine and Growth Factor Reviews - October 30, 2014 Category: Molecular Biology Authors: Mandar Bawadekar, Marco De Andrea, Marisa Gariglio, Santo Landolfo Tags: Mini review Source Type: research
An inflammatory triangle in psoriasis: TNF, type I IFNs and IL-17
Psoriasis is a skin disease where various cytokines play a detrimental role, yet our understanding of the disease is still limited. TNF is a validated drug target in psoriasis and other autoimmune diseases, but its use is associated with side effects. Some paradoxical side effects of anti-TNF treatment are supposedly associated with type I IFNs, which are also implicated in the pathogenesis of psoriasis. Recently, the IL-23/IL-17 axis has been associated with psoriasis as well, and new drugs targeting this axis have already been developed. (Source: Cytokine and Growth Factor Reviews)
Source: Cytokine and Growth Factor Reviews - October 30, 2014 Category: Molecular Biology Authors: Lynda Grine, Lien Dejager, Claude Libert, Roosmarijn E. Vandenbroucke Tags: Survey Source Type: research
IFN-β and Multiple Sclerosis: From Etiology to Therapy and Back
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) characterized, in its most common clinical presentation, by an unpredictable occurrence of relapse and remission phases [1–3]. The disease generally affects young adults [4], with a preference for female gender, as observed in many other immune-mediated conditions. Being a multifactorial disorder, its etiology involves both genetic and environmental risk factors. So far, genome-wide association studies (GWAS) have shown that genetic predisposition to MS is determined by more than 100 disease-associated susceptibility poly...
Source: Cytokine and Growth Factor Reviews - October 30, 2014 Category: Molecular Biology Authors: V. Annibali, R. Mechelli, S. Romano, M.C. Buscarinu, A. Fornasiero, R. Umeton, V.A.G. Ricigliano, F. Orzi, E.M. Coccia, M. Salvetti, G. Ristori Source Type: research
Type I IFN family members: similarity, differences and interaction
Interferons (IFN) are key cytokines with multifaceted antiviral and cell-modulatory properties. Three distinct types of IFN are recognized (I-III) based on structural features, receptor usage, cellular source and biological activities. The action of IFNs is mediated by a complex, partially overlapping, transcriptional program initiated by the interaction with specific receptors. Genetic diversity, with polymorphisms and mutations, can modulate the extent of IFN responses and the susceptibility to infections. (Source: Cytokine and Growth Factor Reviews)
Source: Cytokine and Growth Factor Reviews - October 30, 2014 Category: Molecular Biology Authors: Maria Rosaria Capobianchi, Elena Uleri, Claudia Caglioti, Antonina Dolei Source Type: research
Divergent effects of type-I interferons on regulatory T cells
Type-I interferons (IFNs), namely IFN-α and IFN-β families, have been initially characterized in the light of their ability to interfere with viral infections in several types of somatic cells. Many other activities have been soon identified, including those directed toward cells of the immune system, which possibly represent the most relevant manifestations of the IFN system [1]. Virtually all aspects of an immune response can be modulated by type-I IFNs, in line with the widespread expression of their receptors and with the extensive impact of their signals on gene expression modulation. (Source: Cytokine and Growth Factor Reviews)
Source: Cytokine and Growth Factor Reviews - October 30, 2014 Category: Molecular Biology Authors: Silvia Piconese, Ilenia Pacella, Eleonora Timperi, Vincenzo Barnaba Source Type: research
Type I IFN – A blunt spear in fighting HIV-1 infection
The IFN system is made of a heterogenous class of soluble mediators that interfere with the replication of all varieties of viruses and are specialized in coordinating host responses in a cell type-specific, but virus-non-specific manner. The interferons (IFNs) are classified into three groups: type I or “viral IFN” (IFN-α, IFN-β, IFN-ω, IFN-ɛ and IFN-κ), type II (IFN-γ), and type III (IFN-λ 1, IFN-λ 2 and IFN-λ 3), based on the structure of their receptors on the cell surface. Each type I IFN is encoded by a single gene with the exception of IFN-α, which comprises 13 subtypes in humans [1,2]. (Source: Cytoki...
Source: Cytokine and Growth Factor Reviews - October 29, 2014 Category: Molecular Biology Authors: Chiara Acchioni, Giulia Marsili, Edvige Perrotti, Anna Lisa Remoli, Marco Sgarbanti, Angela Battistini Tags: Survey Source Type: research
Type I IFN- a blunt spear in fighting HIV-1 infection
The IFN system is made of an heterogenous class of soluble mediators that interfere with the replication of all varieties of viruses and are specialized in coordinating host responses in a cell type-specific, but virus-non specific manner. The interferons (IFNs) are classified into three groups: type I or “viral IFN” (IFN-α, IFN-β, IFN-ω, IFN-ɛ and IFN-κ), type II (IFN-γ), and type III (IFN-λ 1, IFN-λ 2 and IFN-λ 3), based on the structure of their receptors on the cell surface. Each type I IFN is encoded by a single gene with the exception of IFN-α, which comprises 13 subtypes in humans [1,2]. (Source: Cytok...
Source: Cytokine and Growth Factor Reviews - October 29, 2014 Category: Molecular Biology Authors: Chiara Acchioni, Giulia Marsili, Edvige Perrotti, Anna Lisa Remoli, Marco Sgarbanti, Angela Battistini Tags: Survey Source Type: research
Hemophagocytic lymphohistiocytosis (HLH): A heterogeneous spectrum of cytokine-driven immune disorders
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder that was first described by Scott and Robb-Smith in 1939 [1]. It is characterized by severe systemic inflammation caused by uncontrolled proliferation and activation of lymphocytes and macrophages, secreting large amounts of cytokines, creating a so-called cytokine storm. The hallmark of HLH is the emergence of hemophagocytosis, a process in which histiocytes actively engulf blood cells and their precursors. Table 1 provides a comprehensive overview of symptoms that are most commonly observed in HLH [2–4], together with their application in the...
Source: Cytokine and Growth Factor Reviews - October 28, 2014 Category: Molecular Biology Authors: Ellen Brisse, Carine H. Wouters, Patrick Matthys Tags: Survey Source Type: research
Hemophagocytic lymphohistiocytosis (hlh), a heterogeneous spectrum of cytokine-driven immune disorders
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder that was first described by Scott and Robb-Smith in 1939 [1]. It is characterized by severe systemic inflammation caused by uncontrolled proliferation and activation of lymphocytes and macrophages, secreting large amounts of cytokines, creating a so-called cytokine storm. The hallmark of HLH is the emergence of hemophagocytosis, a process in which histiocytes actively engulf blood cells and their precursors. Table 1 provides a comprehensive overview of symptoms that are most commonly observed in HLH [2–4], together with their application in the...
Source: Cytokine and Growth Factor Reviews - October 28, 2014 Category: Molecular Biology Authors: Ellen Brisse, Carine H. Wouters, Patrick Matthys Tags: Survey Source Type: research
Introduction to Innate Sensing and Response to Pathogens
Cytokine and Growth Factor Reviews is pleased to highlight recent advances in the field of innate immune responses to microbial pathogens with this Special Issue of CGFR entitled: Innate Sensing and Response to Pathogens. We have assembled an outstanding collection of reviews from international leaders in their respective fields of innate immunity. Our compendium is by no means a complete evaluation of all aspects of innate immunity; this volume rather places a particular focus on the interplay between the host innate immune response and human pathogenic viruses – mechanisms of recognition and signaling, innate evasion m...
Source: Cytokine and Growth Factor Reviews - October 1, 2014 Category: Molecular Biology Authors: John Hiscott Source Type: research
Editorial Board and Publication information
(Source: Cytokine and Growth Factor Reviews)
Source: Cytokine and Growth Factor Reviews - October 1, 2014 Category: Molecular Biology Source Type: research
Negative regulation of RelA phosphorylation: Emerging players and their roles in cancer
Nuclear factor-kappa B (NF-κB) was discovered more than 20 years ago as a protein that when localized to the nucleus binds a response element the immunoglobulin κ enhancer to regulate expression of the κB light chain in B cells [1]. Dimerization of family members through Rel homology domain (RHD) is required for DNA binding and the transcription activation domain (TAD), present in RelA, c-Rel, and RelB, is necessary for upregulation of gene expression. Dimers composed of p50/p65, p50/c-rel, p65/p65, and p65/c-rel possess transcriptional potential, with the p50 and RelA being most intensively studied. (Source: Cytokine a...
Source: Cytokine and Growth Factor Reviews - September 30, 2014 Category: Molecular Biology Authors: Xinyuan Lu, Wendell G. Yarbrough Tags: Mini review Source Type: research
Interleukin-15: New kid on the block for antitumor combination therapy
Interleukin (IL)-15 is one of the most promising molecules to be used in antitumor immune therapy, as it is able to stimulate the main killer cells of both the innate and adaptive immune system. Although this cytokine can be used as a stand-alone immunotherapeutic agent, IL-15 will probably be most efficient in combination with other strategies to overcome high tumor burden, immune suppression of the tumor microenvironment and/or the short half-life of IL-15. In this review, we will discuss the combination strategies with IL-15 that have been tested to date in different animal tumor models, which include chemotherapy, othe...
Source: Cytokine and Growth Factor Reviews - September 25, 2014 Category: Molecular Biology Authors: Johan M.J. Van den Bergh, Viggo F.I. Van Tendeloo, Evelien L.J.M. Smits Tags: Mini review Source Type: research
