scholarly journals Contribution of Interleukin-6 to the Pathogenesis of Systemic Sclerosis

2017 ◽  
Vol 2 (2_suppl) ◽  
pp. S6-S12 ◽  
Author(s):  
Yasushi Kawaguchi
Keyword(s):  
Clinical Trials ◽  
Growth Factors ◽  
Systemic Sclerosis ◽  
Interleukin 6 ◽  
Systemic Circulation ◽  
Unknown Etiology ◽  
Tissue Fibrosis ◽  
Biological Features ◽  
The Past

Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology, manifesting in patients as tissue fibrosis, endothelial dysfunction, and inflammation. The disease is characterized by autoantibodies, a hallmark of autoimmunity. Various cytokines and growth factors are elevated in the systemic circulation and fibrotic lesions of patients with SSc. In particular, several studies over the past 2 decades have shown that interleukin-6 (IL-6) appears to be involved in the pathogenesis of SSc. Based on the association between aberrant IL-6 production and tissue fibrosis in patients with SSc, the anti-IL-6 receptor antibody, tocilizumab, is being investigated in clinical trials. This article reviews the biological features of IL-6 and the IL-6 receptor; the role of IL-6 in the pathogenesis of SSc; and the potential for IL-6 inhibition to be used in the treatment of patients with SSc.

scholarly journals Role of Growth Factors in the Pathogenesis of Tissue Fibrosis in Systemic Sclerosis

2010 ◽  
Vol 6 (4) ◽  
pp. 283-294 ◽  
Author(s):  
Sergio A. Jimenez ◽  
Susan V. Castro ◽  
Sonsoles Piera-Velazquez
Keyword(s):  
Growth Factors ◽  
Systemic Sclerosis ◽  
Tissue Fibrosis

scholarly journals The Many Faces of Interleukin-6: The Role of IL-6 in Inflammation, Vasculopathy, and Fibrosis in Systemic Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Theresa C. Barnes ◽  
Marina E. Anderson ◽  
Robert J. Moots
Keyword(s):  
Systemic Sclerosis ◽  
Endothelial Cell ◽  
Interleukin 6 ◽  
Signalling Pathways ◽  
Endothelial Cell Dysfunction ◽  
Potential Therapeutic Target ◽  
Cell Dysfunction ◽  
Significant Interest ◽  
The Many

Interleukin-6 is currently attracting significant interest as a potential therapeutic target in systemic sclerosis (SSc). In this paper, the biology of interleukin-6 is reviewed, and the evidence for interleukin-6 dysregulation in SSc is explored. The role of inteleukin-6 classical and trans signalling pathways in SSc relevant phenomena such as chronic inflammation, autoimmunity, endothelial cell dysfunction, and fibrogenesis is discussed. The existing evidence that interventions designed to block interleukin-6 signalling are of therapeutic relevance in SSc is evaluated.

scholarly journals The Role of PPAR Gamma in Systemic Sclerosis

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Andréa Tavares Dantas ◽  
Michelly Cristiny Pereira ◽  
Moacyr Jesus Barreto de Melo Rego ◽  
Laurindo Ferreira da Rocha ◽  
Ivan da Rocha Pitta ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Lung Fibrosis ◽  
Ppar Gamma ◽  
Immune Dysregulation ◽  
Unknown Etiology ◽  
Internal Organs ◽  
Medical Need

Fibrosis is recognized as an important feature of many chronic diseases, such as systemic sclerosis (SSc), an autoimmune disease of unknown etiology, characterized by immune dysregulation and vascular injury, followed by progressive fibrosis affecting the skin and multiple internal organs. SSc has a poor prognosis because no therapy has been shown to reverse or arrest the progression of fibrosis, representing a major unmet medical need. Recently, antifibrotic effects of PPARγligands have been studiedin vitroandin vivoand some theories have emerged leading to new insights. Aberrant PPARγfunction seems to be implicated in pathological fibrosis in the skin and lungs. This antifibrotic effect is mainly related to the inhibition of TGF-β/Smad signal transduction but other pathways can be involved. This review focused on recent studies that identified PPARγas an important novel pathway with critical roles in regulating connective tissue homeostasis, with emphasis on skin and lung fibrosis and its role on systemic sclerosis.

scholarly journals Pathogenic Roles of Autoantibodies and Aberrant Epigenetic Regulation of Immune and Connective Tissue Cells in the Tissue Fibrosis of Patients with Systemic Sclerosis

2020 ◽  
Vol 21 (9) ◽  
pp. 3069
Author(s):  
Chang-Youh Tsai ◽  
Song-Chou Hsieh ◽  
Tsai-Hung Wu ◽  
Ko-Jen Li ◽  
Chieh-Yu Shen ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Th2 Cells ◽  
Limited Data ◽  
Autoantibody Production ◽  
Tissue Fibrosis ◽  
Epigenetic Modifiers ◽  
Non Coding Rnas ◽  
Collagen Genes ◽  
Molecular Bases

Systemic sclerosis (SSc) is a multi-system autoimmune disease with tissue fibrosis prominent in the skin and lung. In this review, we briefly describe the autoimmune features (mainly autoantibody production and cytokine profiles) and the potential pathogenic contributors including genetic/epigenetic predisposition, and environmental factors. We look in detail at the cellular and molecular bases underlying tissue-fibrosis which include trans-differentiation of fibroblasts (FBs) to myofibroblasts (MFBs). We also state comprehensively the pro-inflammatory and pro-fibrotic cytokines relevant to MFB trans-differentiation, vasculopathy-associated autoantibodies, and fibrosis-regulating microRNAs in SSc. It is conceivable that tissue fibrosis is mainly mediated by an excessive production of TGF-β, the master regulator, from the skewed Th2 cells, macrophages, fibroblasts, myofibroblasts, and keratinocytes. After binding with TGF-β receptors on MFB, the downstream Wnt/β-catenin triggers canonical Smad 2/3 and non-canonical Smad 4 signaling pathways to transcribe collagen genes. Subsequently, excessive collagen fiber synthesis and accumulation as well as tissue fibrosis ensue. In the later part of this review, we discuss limited data relevant to the role of long non-coding RNAs (lncRNAs) in tissue-fibrosis in SSc. It is expected that these lncRNAs may become the useful biomarkers and therapeutic targets for SSc in the future. The prospective investigations in the development of novel epigenetic modifiers are also suggested.

scholarly journals Small Is Beautiful: Insulin-Like Growth Factors and Their Role in Growth, Development, and Cancer

2010 ◽  
Vol 28 (33) ◽  
pp. 4985-4995 ◽  
Author(s):  
Robert G. Maki
Keyword(s):  
Growth Factors ◽  
Cross Resistance ◽  
Epithelial Cancers ◽  
The Past ◽  
Recent Developments ◽  
History Of ◽  
Growth Development ◽  
Cell Signaling Pathways ◽  
Insulin Like Growth Factors

Insulin-like growth factors were discovered more than 50 years ago as mediators of growth hormone that effect growth and differentiation of bone and skeletal muscle. Interest of the role of insulin-like growth factors in cancer reached a peak in the 1990s, and then waned until the availability in the past 5 years of monoclonal antibodies and small molecules that block the insulin-like growth factor 1 receptor. In this article, we review the history of insulin-like growth factors and their role in growth, development, organism survival, and in cancer, both epithelial cancers and sarcomas. Recent developments regarding phase I to II clinical trials of such agents are discussed, as well as potential studies to consider in the future, given the lack of efficacy of one such monoclonal antibody in combination with cytotoxic chemotherapy in a first-line study in metastatic non–small-cell lung adenocarcinoma. Greater success with these agents clinically is expected when combining the agents with inhibitors of other cell signaling pathways in which cross-resistance has been observed.

Role of microRNA in the pathogenesis of systemic sclerosis tissue fibrosis and vasculopathy

2019 ◽  
Vol 18 (11) ◽  
pp. 102396 ◽  
Author(s):  
Tyler W. Henry ◽  
Fabian A. Mendoza ◽  
Sergio A. Jimenez
Keyword(s):  
Systemic Sclerosis ◽  
Tissue Fibrosis

Microscopy as a Tool in Understanding the Role of Growth Factors in Cardiac Development

1999 ◽  
Vol 5 (S2) ◽  
pp. 1082-1083
Author(s):  
Robert L. Price ◽  
Thomas E. Thielen ◽  
Thomas K. Borg ◽  
Louis Terracio
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Normal Development ◽  
Cardiac Development ◽  
The Past ◽  
Naturally Occurring ◽  
Temporal And Spatial ◽  
Valve Formation ◽  
Factor Function

Over the past several years the central roles of several different growth factors in the normal development of the embryonic heart have been identified through a variety of techniques involving microscopy. Initially, most studies consisted of descriptions of gross changes in cardiac morphology associated with naturally occurring mutations that affected growth factor function. More recently the development of specific probes for growth factor receptors that can be used in confocal microscopy have aided in the identification of changes in the temporal and spatial distributions of receptors at various stages of development. The correlation of these changes with developmental events such as valve formation and trabeculation in the heart, in conjunction with biochemical studies and blocking agents for the growth factors have significantly increased our understanding of growth factor function in cardiac development.

scholarly journals Inflammatory Mechanisms of Idiopathic Epiretinal Membrane Formation

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Malav Joshi ◽  
Shivi Agrawal ◽  
John Byron Christoforidis
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Glial Cells ◽  
Transforming Growth Factor ◽  
Epiretinal Membranes ◽  
Ultrastructural Studies ◽  
The Past ◽  
Cells Of Origin ◽  
Immunohistochemical Techniques

The pathogenesis of idiopathic epiretinal membranes (iERMs), a common pathology found in retina clinics, still eludes researchers to date. Ultrastructural studies of iERMs in the past have failed to identify the cells of origin due to the striking morphologic changes of cells involved via transdifferentiation. Thus, immunohistochemical techniques that stain for the cytostructural components of cells have confirmed the importance of glial cells and hyalocytes in iERM formation. The cellular constituents of iERMs are thought to consist of glial cells, fibroblasts, hyalocytes, etc. that, in concert with cytokines and growth factors present in the vitreous, lead to iERM formation. Recently, research has focused on the role of the posterior hyaloid in iERM formation and contraction, particularly the process of anomalous PVD as it relates to iERM formation. Recent advances in proteomics techniques have also elucidated the growth factors and cytokines involved in iERM formation, most notably nerve growth factor, glial cell line-derived growth factor, and transforming growth factorβ1.

scholarly journals Cryptosporidiosis.

1991 ◽  
Vol 4 (3) ◽  
pp. 325-358 ◽  
Author(s):  
W L Current ◽  
L S Garcia
Keyword(s):  
Case Reports ◽  
Basic Research ◽  
Diagnostic Techniques ◽  
Biomedical Literature ◽  
Unknown Etiology ◽  
Diarrheal Illness ◽  
Cryptosporidium Spp ◽  
The Past ◽  
Present Understanding

Before 1982, only eight case reports of human cryptosporidiosis and fewer than 30 papers on Cryptosporidium spp. appeared in the biomedical literature. At that time, cryptosporidiosis was thought to be an infrequent infection in animals and rarely an opportunistic infection in humans. The concept of Cryptosporidium spp. as pathogens has changed dramatically within the past 8 years because of improved diagnostic techniques, increased awareness within the biomedical community, and the development of basic research programs in numerous laboratories. Presently, greater than 1,000 publications including over 400 case reports in the biomedical literature address Cryptosporidium spp. and cryptosporidiosis. Cryptosporidium parvum is now thought to be one of the three most common enteropathogens causing diarrheal illness in humans worldwide, especially in developing countries. It is likely that cryptosporidiosis was previously included in the 25 to 35% of diarrheal illness with unknown etiology. Because of the severity and length of diarrheal illness and because no effective therapy has been identified, cryptosporidiosis is one of the most ominous infections associated with AIDS. The role of C. parvum as an enteropathogen is well established; documentation of its role as a cause of hepatobiliary and respiratory diseases is now appearing in the literature. Our present understanding of the natural history, epidemiology, biology, and immunology of Cryptosporidium spp. as well as the clinical features, pathogenicity, and treatment of cryptosporidiosis are reviewed here.

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