scholarly journals 12 Weeks of Combined Endurance and Resistance Training Reduces Innate Markers of Inflammation in a Randomized Controlled Clinical Trial in Patients with Multiple Sclerosis

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Nathalie Deckx ◽  
Inez Wens ◽  
Amber H. Nuyts ◽  
Niel Hens ◽  
Benedicte Y. De Winter ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Inflammatory Mediators ◽  
Exercise Program ◽  
Underlying Disease ◽  
Peripheral Tolerance ◽  
Controlled Clinical Trial ◽  
Tissue Mass ◽  
Markers Of Inflammation ◽  
And Function

Previously, we reported that patients with multiple sclerosis (MS) demonstrate improved muscle strength, exercise tolerance, and lean tissue mass following a combined endurance and resistance exercise program. However, the effect of exercise on the underlying disease pathogenesis remains elusive. Since recent evidence supports a crucial role of dendritic cells (DC) in the pathogenesis of MS, we investigated the effect of a 12-week combined exercise program in MS patients on the number and function of DC. We demonstrate an increased number of plasmacytoid DC (pDC) following the exercise program. These pDC display an activated phenotype, as evidenced by increased numbers of circulating CD62L+and CD80+pDC. Interestingly, the number of CD80+pDC positively correlates with the presence of IL-10-producing regulatory type 1 cells (Tr1), an important cell type for maintaining peripheral tolerance to self-antigens. In addition, decreased production of the inflammatory mediators, TNF-αand MMP-9, upon Toll-like receptor (TLR) stimulation was found at the end of the exercise program. Overall, our findings suggest that the 12-week exercise program reduces the secretion of inflammatory mediators upon TLR stimulation and promotes the immunoregulatory function of circulating pDC, suggestive for a favorable impact of exercise on the underlying immunopathogenesis of MS.

scholarly journals Potential Role of Trace Elements (Al, Cu, Zn, and Se) in Multiple Sclerosis Physiopathology

2020 ◽  
Vol 27 (4) ◽  
pp. 163-177
Author(s):  
Mohammad Sadegh Hesamian ◽  
Nahid Eskandari
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Trace Elements ◽  
Plasma Cells ◽  
Peripheral Tolerance ◽  
The Central Nervous System ◽  
Living Organisms ◽  
Tolerance Breakdown ◽  
Peripheral Immune Cells

Multiple sclerosis (MS) is an unpredictable disease of the central nervous system. The cause of MS is not known completely, and pathology is specified by involved demyelinated areas in the white and gray matter of the brain and spinal cord. Inflammation and peripheral tolerance breakdown due to Treg cell defects and/or effector cell resistance are present at all stages of the disease. Several invading peripheral immune cells are included in the process of the disease such as macrophages, CD8+ T cells, CD4+ T cells, B cells, and plasma cells. Trace elements are known as elements found in soil, plants, and living organisms in small quantities. Some of them (e.g., Al, Cu, Zn, Mn, and Se) are essential for the body’s functions like catalysts in enzyme systems, energy metabolism, etc. Al toxicity and Cu, Zn, and Se toxicity and deficiency can affect the immune system and following neuron inflammation and degeneration. These processes may result in MS pathology. Of course, factors such as lifestyle, environment, and industrialization can affect levels of trace elements in the human body.

scholarly journals The control of inflammation via the phosphorylation and dephosphorylation of tristetraprolin: a tale of two phosphatases

2016 ◽  
Vol 44 (5) ◽  
pp. 1321-1337 ◽  
Author(s):  
Andrew R. Clark ◽  
Jonathan L.E. Dean
Keyword(s):  
Inflammatory Mediators ◽  
Knockout Mouse ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Human Orthologue ◽  
And Function ◽  
Detailed Picture ◽  
Lines Of Evidence

Twenty years ago, the first description of a tristetraprolin (TTP) knockout mouse highlighted the fundamental role of TTP in the restraint of inflammation. Since then, work from several groups has generated a detailed picture of the expression and function of TTP. It is a sequence-specific RNA-binding protein that orchestrates the deadenylation and degradation of several mRNAs encoding inflammatory mediators. It is very extensively post-translationally modified, with more than 30 phosphorylations that are supported by at least two independent lines of evidence. The phosphorylation of two particular residues, serines 52 and 178 of mouse TTP (serines 60 and 186 of the human orthologue), has profound effects on the expression, function and localisation of TTP. Here, we discuss the control of TTP biology via its phosphorylation and dephosphorylation, with a particular focus on recent advances and on questions that remain unanswered.

scholarly journals Role of PGE-2 and Other Inflammatory Mediators in Skin Aging and Their Inhibition by Topical Natural Anti-Inflammatories

Cosmetics ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. 6 ◽  
Author(s):  
Bryan Fuller
Keyword(s):  
Skin Cancer ◽  
Inflammatory Mediators ◽  
Normal Skin ◽  
Sun Exposure ◽  
Skin Aging ◽  
Tnf Alpha ◽  
Dermal Matrix ◽  
Chronological Aging ◽  
And Function

Human skin aging is due to two types of aging processes, “intrinsic” (chronological) aging and “extrinsic” (external factor mediated) aging. While inflammatory events, triggered mainly by sun exposure, but also by pollutants, smoking and stress, are the principle cause of rapid extrinsic aging, inflammation also plays a key role in intrinsic aging. Inflammatory events in the skin lead to a reduction in collagen gene activity but an increase in activity of the genes for matrix metalloproteinases. Inflammation also alters proliferation rates of cells in all skin layers, causes thinning of the epidermis, a flattening of the dermo-epidermal junction, an increase in irregular pigment production, and, finally, an increased incidence of skin cancer. While a large number of inflammatory mediators, including IL-1, TNF-alpha and PGE-2, are responsible for many of these damaging effects, this review will focus primarily on the role of PGE-2 in aging. Levels of this hormone-like mediator increase quickly when skin is exposed to ultraviolet radiation (UVR), causing changes in genes needed for normal skin structure and function. Further, PGE-2 levels in the skin gradually increase with age, regardless of whether or not the skin is protected from UVR, and this smoldering inflammation causes continuous damage to the dermal matrix. Finally, and perhaps most importantly, PGE-2 is strongly linked to skin cancer. This review will focus on: (1) the role of inflammation, and particularly the role of PGE-2, in accelerating skin aging, and (2) current research on natural compounds that inhibit PGE-2 production and how these can be developed into topical products to retard or even reverse the aging process, and to prevent skin cancer.

scholarly journals Synaptic Dysfunction in Multiple Sclerosis: A Red Thread from Inflammation to Network Disconnection

2021 ◽  
Vol 22 (18) ◽  
pp. 9753
Author(s):  
Laura Bellingacci ◽  
Andrea Mancini ◽  
Lorenzo Gaetani ◽  
Alessandro Tozzi ◽  
Lucilla Parnetti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Networks ◽  
Chronic Inflammatory Disease ◽  
Brain Network ◽  
Structure And Function ◽  
Synaptic Dysfunction ◽  
Synaptic Failure ◽  
And Function ◽  
Synaptic Structures

Multiple sclerosis (MS) has been clinically considered a chronic inflammatory disease of the white matter; however, in the last decade growing evidence supported an important role of gray matter pathology as a major contributor of MS-related disability and the involvement of synaptic structures assumed a key role in the pathophysiology of the disease. Synaptic contacts are considered central units in the information flow, involved in synaptic transmission and plasticity, critical processes for the shaping and functioning of brain networks. During the course of MS, the immune system and its diffusible mediators interact with synaptic structures leading to changes in their structure and function, influencing brain network dynamics. The purpose of this review is to provide an overview of the existing literature on synaptic involvement during experimental and human MS, in order to understand the mechanisms by which synaptic failure eventually leads to brain networks alterations and contributes to disabling MS symptoms and disease progression.

scholarly journals Impact of Andropause on Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria C. Ysrraelit ◽  
Jorge Correale
Keyword(s):  
Multiple Sclerosis ◽  
Age Of Onset ◽  
Adaptive Immune Response ◽  
Epidemiological Studies ◽  
Testosterone Levels ◽  
Adaptive Immune ◽  
Natural Decrease ◽  
And Function ◽  
Gonadal Failure

Andropause results from the natural decrease in testosterone levels that occurs with age. In contrast to menopause, which is a universal, well-characterized process associated with absolute gonadal failure, andropause ensues after gradual decline of both hypothalamic-pituitary-gonadal axis activity, as well as of testicular function, a process which usually develops over a period of many years. Increasing evidence on greater risk of Multiple sclerosis (MS) associated with lower testosterone levels is being reported. Likewise, epidemiological studies have shown a later age of onset of MS in men, relative to women, which could perhaps respond to the decline in protective testosterone levels. In this review, we will discuss the role of androgens in the development and function of the innate and adaptive immune response, as well as in neuroprotective mechanisms relevant to MS. Testosterone effects observed in different animal models and in epidemiological studies in humans will be discussed, as well as their correlation with physical disability and cognitive function levels. Finally, published and ongoing clinical trials exploring the role of androgens, particularly at key stages of sexual maturation, will be reviewed.

scholarly journals MicroRNAs and Multiple Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-27 ◽  
Author(s):  
Kemal Ugur Tufekci ◽  
Meryem Gulfem Oner ◽  
Sermin Genc ◽  
Kursad Genc
Keyword(s):  
Multiple Sclerosis ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Mirna Biogenesis ◽  
Disease Marker ◽  
Organ Specific ◽  
And Function

MicroRNAs (miRNAs) have recently emerged as a new class of modulators of gene expression. miRNAs control protein synthesis by targeting mRNAs for translational repression or degradation at the posttranscriptional level. These noncoding RNAs are endogenous, single-stranded molecules approximately 22 nucleotides in length and have roles in multiple facets of immunity, from regulation of development of key cellular players to activation and function in immune responses. Recent studies have shown that dysregulation of miRNAs involved in immune responses leads to autoimmunity. Multiple sclerosis (MS) serves as an example of a chronic and organ-specific autoimmune disease in which miRNAs modulate immune responses in the peripheral immune compartment and the neuroinflammatory process in the brain. For MS, miRNAs have the potential to serve as modifying drugs. In this review, we summarize current knowledge of miRNA biogenesis and mode of action and the diverse roles of miRNAs in modulating the immune and inflammatory responses. We also review the role of miRNAs in autoimmunity, focusing on emerging data regarding miRNA expression patterns in MS. Finally, we discuss the potential of miRNAs as a disease marker and a novel therapeutic target in MS. Better understanding of the role of miRNAs in MS will improve our knowledge of the pathogenesis of this disease.

scholarly journals Implications the Role of miR-155 in the Pathogenesis of Autoimmune Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Salar Pashangzadeh ◽  
Morteza Motallebnezhad ◽  
Fatemeh Vafashoar ◽  
Azadeh Khalvandi ◽  
Nazanin Mojtabavi
Keyword(s):  
Immune System ◽  
Autoimmune Diseases ◽  
Immune Cell ◽  
Large Body ◽  
Peripheral Tolerance ◽  
Target Cells ◽  
Altered Expression ◽  
Post Translational Modifications ◽  
And Function

MicroRNAs (miRNAs) are small noncoding conserved RNAs containing 19 to 24 nucleotides that are regulators of post-translational modifications and are involved in the majority of biological processes such as immune homeostasis, T helper cell differentiation, central and peripheral tolerance, and immune cell development. Autoimmune diseases are characterized by immune system dysregulation, which ultimately leads to destructive responses to self-antigens. A large body of literature suggests that autoimmune diseases and immune dysregulation are associated with different miRNA expression changes in the target cells and tissues of adaptive or innate immunity. miR-155 is identified as a critical modulator of immune responses. Recently conducted studies on the expression profile of miR-155 suggest that the altered expression and function of miR-155 can mediate vulnerability to autoimmune diseases and cause significant dysfunction of the immune system.

scholarly journals miRNAs in Microglia: Important Players in Multiple Sclerosis Pathology

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142098118
Author(s):  
Alexander D. Walsh ◽  
Linda T. Nguyen ◽  
Michele D. Binder
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Approaches ◽  
Ribonucleic Acids ◽  
Microglial Phagocytosis ◽  
The Central Nervous System ◽  
And Function ◽  
Ms Pathogenesis

Microglia are the resident immune cells of the central nervous system and important regulators of brain homeostasis. Central to this role is a dynamic phenotypic plasticity that enables microglia to respond to environmental and pathological stimuli. Importantly, different microglial phenotypes can be both beneficial and detrimental to central nervous system health. Chronically activated inflammatory microglia are a hallmark of neurodegeneration, including the autoimmune disease multiple sclerosis (MS). By contrast, microglial phagocytosis of myelin debris is essential for resolving inflammation and promoting remyelination. As such, microglia are being explored as a potential therapeutic target for MS. MicroRNAs (miRNAs) are short non-coding ribonucleic acids that regulate gene expression and act as master regulators of cellular phenotype and function. Dysregulation of certain miRNAs can aberrantly activate and promote specific polarisation states in microglia to modulate their activity in inflammation and neurodegeneration. In addition, miRNA dysregulation is implicated in MS pathogenesis, with circulating biomarkers and lesion specific miRNAs identified as regulators of inflammation and myelination. However, the role of miRNAs in microglia that specifically contribute to MS progression are still largely unknown. miRNAs are being explored as therapeutic agents, providing an opportunity to modulate microglial function in neurodegenerative diseases such as MS. This review will focus firstly on elucidating the complex role of microglia in MS pathogenesis. Secondly, we explore the essential roles of miRNAs in microglial function. Finally, we focus on miRNAs that are implicated in microglial processes that contribute directly to MS pathology, prioritising targets that could inform novel therapeutic approaches to MS.

Perceived Health and Functional Status and Work Environmental Factors as Determinants of Psychological Stress Among Employed People With Multiple Sclerosis

2020 ◽  
Vol 34 (3) ◽  
pp. 145-158 ◽  
Author(s):  
Jian Li ◽  
Phillip Rumrill ◽  
Malachy Bishop ◽  
Mykal Leslie
Keyword(s):  
Multiple Sclerosis ◽  
Environmental Factors ◽  
Psychological Stress ◽  
Perceived Stress ◽  
Career Decision Making ◽  
Lower Stress ◽  
Hierarchical Multiple Regression ◽  
Final Model ◽  
And Function

PurposeThis correlational study examined relationships among (a) health and function factors, (b) work environmental factors, and (c) perceived psychological stress among employed people with multiple sclerosis (MS).MethodBased on responses to a national survey by 523 employed people with MS, this study used a hierarchical multiple regression analysis.ResultsThe final model explained 30% of the variability in participants' perceived stress scores. Participants who perceived better overall health, who experienced less severe cognitive impairment, who expressed higher levels of job satisfaction, and who did not receive accommodations at work reported lower stress scores than did other participants.ImplicationsThe important role of stress in employment and career decision-making underscores the value of tailored psychosocial, medical, and vocational interventions for employed people with MS.

Sign in / Sign up

Export Citation Format

Share Document