Cytokine & Growth Factor Reviews RSS feed: Current Issue. Cytokine & Growth Factor Reviews publishes thought-provoking articles (critical reviews, state-of-the-art reviews, letters to the editor, meeting reviews) devoted to important advances in the rapidly changing fields of growth factor and cytokine research. Major emphasis is placed on the multidisciplinary significance of cytokines and growth factors in areas as diverse as signal transduction, cell growth and differentiation, embryonic development, immunology, tumorigenesis and clinical medicine. http://www.cgfr.co.uk/?rss=yesElsevier Inc.en © 2011 Published by Elsevier Inc. All rights reserved. Cytokine & Growth Factor Reviews1359-6101225-6October 2011 © 2011 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.cgfr.co.uk/article/PIIS1359610111000633/abstract?rss=yesEditorial Board10.1016/S1359-6101(11)00063-3Cytokine & Growth Factor Reviews 22, 5 (2011)2011-10-01Cytokine & Growth Factor Reviews2011-10-01225-6S1359-6101(11)X0006-0CO2CO2http://www.cgfr.co.uk/article/PIIS135961011100061X/abstract?rss=yesAt first glance an entire issue of a journal devoted to “Cytokine research in Belgium” is a somewhat bizarre way of assembling a series of reviews. Has a survey been done of cytokine paper output per 1000 square miles or per population of 10 million, and was Belgium in the top ranking? I doubt it. Or is there another reason for a particular clustering? Perhaps the answer has to be found in the saying that scientists stand on the shoulders of their predecessors.Cytokine research in BelgiumWalter Fiers10.1016/j.cytogfr.2011.11.008Cytokine & Growth Factor Reviews 22, 5 (2011)2011-10-01Cytokine & Growth Factor Reviews2011-10-01225-6S1359-6101(11)X0006-0255256http://www.cgfr.co.uk/article/PIIS1359610111000451/abstract?rss=yesAbstract: Members of the family of NOD-like receptors (NLRs) play essential roles in innate immunity by detecting intracellular ‘pathogen-associated molecular patterns’ (PAMPs) and ‘danger-associated molecular patterns’ (DAMPs). These molecules reveal the presence of pathogenic infection, abiotic stress, environmental insults, cellular damage, and cell death. NLR family members can be divided in two functional groups. One group consists of intracellular receptors, such as NLRP1, NLRP3, NLRP6 and NLRC4, which mediate the assembly of inflammasome complexes leading to the activation of procaspase-1. The second group includes members such as NOD1 and NOD2, and mediates the assembly of complexes that activate MAPK and NF-κB signaling pathways. We review the roles of NLR family members in health and disease, with emphasis on the signaling mechanisms in cell death and inflammation.NOD-like receptors and the innate immune system: Coping with danger, damage and deathKristof Kersse, Mathieu J.M. Bertrand, Mohamed Lamkanfi, Peter Vandenabeele10.1016/j.cytogfr.2011.09.003Cytokine & Growth Factor Reviews 22, 5 (2011)2011-10-13Cytokine & Growth Factor Reviews2011-10-13225-6S1359-6101(11)X0006-0257276http://www.cgfr.co.uk/article/PIIS1359610111000554/abstract?rss=yesAbstract: TNF is a multifunctional cytokine that plays a key role in innate immunity by inducing the expression of a variety of genes that are involved in an inflammatory response. TNF-induced NF-κB activation is one of the best studied signaling pathways in mammalian cells and has recently led to a revival of research in the biology of ubiquitin. Many NF-κB signaling proteins are modified by specific ubiquitin ligases with different types of ubiquitin chains that are recognized by other proteins and which determine the outcome of ubiquitination. In addition, specific de-ubiquitinases make the whole process reversible. This review summarizes recent findings that have shaped our current understanding on the role of cytoplasmic ubiquitination events in the regulation of TNF-induced NF-κB signaling.Regulation of TNF-induced NF-κB activation by different cytoplasmic ubiquitination eventsKelly Verhelst, Isabelle Carpentier, Rudi Beyaert10.1016/j.cytogfr.2011.11.002Cytokine & Growth Factor Reviews 22, 5 (2011)2011-11-28Cytokine & Growth Factor Reviews2011-11-28225-6S1359-6101(11)X0006-0277286http://www.cgfr.co.uk/article/PIIS1359610111000591/abstract?rss=yesAbstract: Signaling by the many ligands of the TGFβ family strongly converges towards only five receptor-activated, intracellular Smad proteins, which fall into two classes i.e. Smad2/3 and Smad1/5/8, respectively. These Smads bind to a surprisingly high number of Smad-interacting proteins (SIPs), many of which are transcription factors (TFs) that co-operate in Smad-controlled target gene transcription in a cell type and context specific manner. A combination of functional analyses in vivo as well as in cell cultures and biochemical studies has revealed the enormous versatility of the Smad proteins. Smads and their SIPs regulate diverse molecular and cellular processes and are also directly relevant to development and disease. In this survey, we selected appropriate examples on the BMP-Smads, with emphasis on Smad1 and Smad5, and on a number of SIPs, i.e. the CPSF subunit Smicl, Ttrap (Tdp2) and Sip1 (Zeb2, Zfhx1b) from our own research carried out in three different vertebrate models.Few Smad proteins and many Smad-interacting proteins yield multiple functions and action modes in TGFβ/BMP signaling in vivoAndrea Conidi, Silvia Cazzola, Karen Beets, Kathleen Coddens, Clara Collart, Frederique Cornelis, Luk Cox, Debruyn Joke, Mariya P. Dobreva, Ruben Dries, Camila Esguerra, Annick Francis, Abdelilah Ibrahimi, Roel Kroes, Flore Lesage, Elke Maas, Ivan Moya, Paulo N.G. Pereira, Elke Stappers, Agata Stryjewska, Veronique van den Berghe, Liesbeth Vermeire, Griet Verstappen, Eve Seuntjens, Lieve Umans, An Zwijsen, Danny Huylebroeck10.1016/j.cytogfr.2011.11.006Cytokine & Growth Factor Reviews 22, 5 (2011)2011-11-28Cytokine & Growth Factor Reviews2011-11-28225-6S1359-6101(11)X0006-0287300http://www.cgfr.co.uk/article/PIIS1359610111000608/abstract?rss=yesAbstract: This review focuses on the biological functions and signalling pathways activated by Lymphotoxin α (LTα)/Lymphotoxin β (LTβ) and their receptor LTβR. Genetic mouse models shed light on crucial roles for LT/LTβR to build and to maintain the architecture of lymphoid organs and to ensure an adapted immune response against invading pathogens. However, chronic inflammation, autoimmunity, cell death or cancer development are disorders that occur when the LT/LTβR system is twisted.Biological inhibitors, such as antagonist antibodies or decoy receptors, have been developed and used in clinical trials for diseases associated to the LT/LTβR system.Recent progress in the understanding of cellular trafficking and NF-κB signalling pathways downstream of LTα/LTβ may bring new opportunities to develop therapeutics that target the pathological functions of these cytokines.Biology and signal transduction pathways of the Lymphotoxin-αβ/LTβR systemCaroline Remouchamps, Layla Boutaffala, Corinne Ganeff, Emmanuel Dejardin10.1016/j.cytogfr.2011.11.007Cytokine & Growth Factor Reviews 22, 5 (2011)2011-10-01Cytokine & Growth Factor Reviews2011-10-01225-6S1359-6101(11)X0006-0301310http://www.cgfr.co.uk/article/PIIS1359610111000463/abstract?rss=yesAbstract: The TNF signaling pathway is a valuable target in the therapy of autoimmune diseases, and anti-TNF drugs are successfully used to treat diseases such as rheumatoid arthritis, Crohn's disease and psoriasis. By their ability to interfere with inflammatory processes at multiple levels, these TNF blockers have become invaluable tools to inhibit the inflammation induced damage and allow recovery of the affected tissues. Unfortunately this therapy has some drawbacks, including increased risk of infection and malignancy, and remarkably, the onset of new auto-immune diseases. Some of these effects are caused by the unwanted abrogation of beneficial TNF signaling. More specific targeting of the pathological TNF-induced signaling might lead to broader applicability and improved safety. Specificity might be increased by inhibiting the soluble TNF/TNFR1 axis while leaving the often beneficial transmembrane TNF/TNFR2 signaling untouched. This approach looks promising because it inhibits the pathological effects of TNF and reduces the side effects, and it opens the way for the treatment of other diseases in which TNFR2 inhibition is detrimental. In this review we give an overview of in vivo mouse studies of TNF mediated pathologies demonstrating that the blockade or genetic deletion of sTNF or TNFR1 is preferable over total TNF blockade.Treatment of TNF mediated diseases by selective inhibition of soluble TNF or TNFR1Filip Van Hauwermeiren, Roosmarijn E. Vandenbroucke, Claude Libert10.1016/j.cytogfr.2011.09.004Cytokine & Growth Factor Reviews 22, 5 (2011)2011-10-03Cytokine & Growth Factor Reviews2011-10-03225-6S1359-6101(11)X0006-0311319http://www.cgfr.co.uk/article/PIIS1359610111000542/abstract?rss=yesAbstract: MAPPIT (mammalian protein–protein interaction trap) is a two-hybrid interaction mapping technique based on functional complementation of a type I cytokine receptor signaling pathway. Over the last decade, the technology has been extended into a platform of complementary assays for the detection of interactions among proteins and between chemical compounds and proteins, and for the identification of small molecules that interfere with protein–protein interactions. Additionally, several screening approaches have been developed to broaden the utility of the platform. In this review we provide an overview of the different components of the MAPPIT toolbox and highlight a number of applications in interactomics, drug screening and compound target profiling.MAPPIT: A protein interaction toolbox built on insights in cytokine receptor signalingSam Lievens, Frank Peelman, Karolien De Bosscher, Irma Lemmens, Jan Tavernier10.1016/j.cytogfr.2011.11.001Cytokine & Growth Factor Reviews 22, 5 (2011)2011-11-28Cytokine & Growth Factor Reviews2011-11-28225-6S1359-6101(11)X0006-0321329http://www.cgfr.co.uk/article/PIIS1359610111000578/abstract?rss=yesAbstract: Chemerin was isolated as the natural ligand of the G protein-coupled receptor ChemR23. Chemerin acts as a chemotactic factor for leukocyte populations expressing ChemR23, particularly immature plasmacytoid dendritic cells, but also immature myeloid DCs, macrophages and natural killer cells. Chemerin is expressed by epithelial and non-epithelial cells as an inactive precursor, present at nanomolar concentrations in plasma. Processing of the precursor C-terminus is required for generating bioactive forms of chemerin. Various proteases mediate this processing, including neutrophil serine proteases and proteases from coagulation and fibrinolytic cascades. ChemR23-expressing cells are recruited in human inflammatory diseases, such as psoriasis and lupus. In animal models, both pro-inflammatory and anti-inflammatory roles of chemerin have been reported. Recently, two other receptors for chemerin were described, GPR1 and CCRL2, but their functional relevance is largely unknown. Both chemerin and ChemR23 are also expressed by adipocytes, and the emerging role of chemerin as an adipokine regulating lipid and carbohydrate metabolism is an area of intense research.Chemerin and its receptors in leukocyte trafficking, inflammation and metabolismBenjamin Bondue, Valérie Wittamer, Marc Parmentier10.1016/j.cytogfr.2011.11.004Cytokine & Growth Factor Reviews 22, 5 (2011)2011-11-28Cytokine & Growth Factor Reviews2011-11-28225-6S1359-6101(11)X0006-0331338http://www.cgfr.co.uk/article/PIIS1359610111000566/abstract?rss=yesAbstract: In this review, we discuss our studies on the pathogenesis of collagen-induced arthritis (CIA) and related mouse models for rheumatoid arthritis. Of note, these models invariably rely on the use of complete Freund's adjuvant (CFA). Our analysis has focused on explaining the dichotomous – either protective or disease-promoting – role of endogenous IFN-γ. Induction of a myelopoietic burst by CFA was identified as an important and underestimated factor in mediating the role of IFN-γ and other cytokines (IL-6, IL-17, GCP-2, RANK-L). Myelopoiesis provides an excess in precursors for joint-infiltrating neutrophils and osteoclasts. We postulate that classical CIA is primarily an auto-inflammatory disease, in part because of a strong innate immune response to the adjuvant. Superimposed on this, collagen-specific auto-immunity reinforces inflammatory reactivity in joints.Collagen-induced arthritis and related animal models: How much of their pathogenesis is auto-immune, how much is auto-inflammatory?Alfons Billiau, Patrick Matthys10.1016/j.cytogfr.2011.11.003Cytokine & Growth Factor Reviews 22, 5 (2011)2011-11-28Cytokine & Growth Factor Reviews2011-11-28225-6S1359-6101(11)X0006-0339344http://www.cgfr.co.uk/article/PIIS135961011100044X/abstract?rss=yesAbstract: Cancer is a life-threatening disease world-wide and colorectal cancer is the second common cause of cancer mortality. The interaction between tumor cells and stromal cells plays a crucial role in tumor initiation and progression and is partially mediated by chemokines. Chemokines predominantly participate in the chemoattraction of leukocytes to inflammatory sites. Nowadays, it is clear that CXC chemokines and their receptors (CXCR) may also modulate tumor behavior by several important mechanisms: regulation of angiogenesis, activation of a tumor-specific immune response by attracting leukocytes, stimulation of tumor cell proliferation and metastasis. Here, we review the expression and complex roles of CXC chemokines (CXCL1 to CXCL16) and their receptors (CXCR1 to CXCR6) in colorectal cancer. Overall, increased expression levels of CXC chemokines correlate with poor prognosis.The expression and role of CXC chemokines in colorectal cancerHannelien Verbeke, Sofie Struyf, Geneviève Laureys, Jo Van Damme10.1016/j.cytogfr.2011.09.002Cytokine & Growth Factor Reviews 22, 5 (2011)2011-10-17Cytokine & Growth Factor Reviews2011-10-17225-6S1359-6101(11)X0006-0345358http://www.cgfr.co.uk/article/PIIS135961011100058X/abstract?rss=yesAbstract: Multiple sclerosis (MS) is an autoimmune disease with a spectrum of clinical evolutions. We here summarize recent insights into the neuroinflammatory processes of demyelination, vascular cuffing, destruction of the blood brain barrier (BBB), neuronal toxicity and the ensuing (re)activation of autoreactive lymphocytes. Translation of these processes in molecular terms indicates that cytokines, including interferons, ligands of the tumor necrosis factor receptor family and interleukins, and also chemokines and matrix metalloproteinases play pivotal roles in MS. This not only helps to understand disease mechanisms in the central nervous system of affected patients, but also forms a solid scientific basis to improve present therapies. Treatment of MS with parenterally administered anti-inflammatory agents may be improved, based on present knowledge and new insights obtained with animal models. Such innovations include better use of knowledge about the formulation, administration, turnover and glycosylation of interferon-β (IFN-β), combinations of IFN-β with inhibitors of IFN-β-degrading proteinases in MS, and new ways to diminish vascular cuffs and the transmigration of leukocytes across the two basement membranes of the BBB. Novel molecules interfering with matrix metalloproteinases and chemokines, such as EMMPRIN, COAM and monoclonal antibodies are currently being investigated, demonstrating continued efforts to find new drugs for MS treatment.Probing cytokines, chemokines and matrix metalloproteinases towards better immunotherapies of multiple sclerosisGhislain Opdenakker, Jo Van Damme10.1016/j.cytogfr.2011.11.005Cytokine & Growth Factor Reviews 22, 5 (2011)2011-11-28Cytokine & Growth Factor Reviews2011-11-28225-6S1359-6101(11)X0006-0359365