scholarly journals Role of Alarmins in the Pathogenesis of Systemic Sclerosis

2020 ◽  
Vol 21 (14) ◽  
pp. 4985 ◽  
Author(s):  
Antonello Giovannetti ◽  
Elisabetta Straface ◽  
Edoardo Rosato ◽  
Marco Casciaro ◽  
Giovanni Pioggia ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Immune Functions ◽  
Internal Organs ◽  
Immune System Activation ◽  
System Activation ◽  
Genetic And Environmental Factors ◽  
Chronic Autoimmune Disease ◽  
And Oxidative Stress ◽  
Organ Fibrosis

Systemic sclerosis (SSc) is a rare chronic autoimmune disease associated with significant morbidity and mortality. Two main subsets of SSc are recognized: (i) diffuse cutaneous SSc with rapidly progressive fibrosis of the skin, lungs, and other internal organs; and (ii) limited cutaneous SSc, which is dominated by vascular manifestations, with skin and organ fibrosis generally limited and slowly progressing. In spite of intense investigation, both etiology and pathogenesis of SSc are still unknown. Genetic and environmental factors, as well as abnormalities of immune functions, are strongly suggested for etiology, while microvascular abnormalities, immune system activation, and oxidative stress are suggested for the pathogenesis. Recently, it has been found that a multitude of mediators and cytokines are implicated in the fibrotic processes observed in SSc. Among these, a central role could be exerted by “alarmins”, endogenous and constitutively expressed proteins/peptides that function as an intercellular signal defense. This review describes, in a detailed manner, the role of alarmins in the pathogenesis of scleroderma.

scholarly journals Comparisons of lung and gluteus transcriptome profiles between yaks at different ages

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jin-Wei Xin ◽  
Zhi-Xin Chai ◽  
Cheng-Fu Zhang ◽  
Qiang Zhang ◽  
Yong Zhu ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Function ◽  
Muscle Injury ◽  
Tibet Plateau ◽  
Immune Functions ◽  
Immune System Activation ◽  
System Activation ◽  
Qinghai Tibet Plateau ◽  
Activation Status

Abstract The yak, Bos grunniens, is the only large mammal in the Qinghai-Tibet Plateau and has been bred to provide meat, milk, and transportation. Previous studies indicate that the immune system contributes to the yak’s adaptation to high-altitude environments. In order to further investigate changes in immune function during yak development, we compared the transcriptome profiles of gluteus and lung tissues among yaks at 6, 30, 60, and 90 months of age. Analyses of significantly differentially expressed genes (DEGs) in lung tissues revealed that immune function was more activated at 6-months and less activated at 90-months than in the 30 and 60-month-old animals. DEG exploration in gluteal tissues revealed that immune functions were more highly activated at both 6 and 90-months, compared with 30 and 60-months. Immune system activation in the muscle and lung tissues of 30-month-old yaks may increase their resistance to infections, while decreased may be due to aging. Furthermore, the higher immune activation status in the gluteal tissues in 90-month-old yaks could be due to muscle injury and subsequent regeneration, which is supported by the fact that 5 unigenes related with muscle injury and 3 related to muscle regeneration displayed greater expression levels at 90-months than at 30 and 60-months. Overall, the present study highlights the important role of the immune system in yak development, which will facilitate future investigations.

scholarly journals Changes in Plasma Phospholipid Metabolism Are Associated with Clinical Manifestations of Systemic Sclerosis

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2116
Author(s):  
Marija Geroldinger-Simić ◽  
Thomas Bögl ◽  
Markus Himmelsbach ◽  
Norbert Sepp ◽  
Wolfgang Buchberger
Keyword(s):  
Systemic Sclerosis ◽  
High Performance ◽  
Clinical Manifestations ◽  
Plasma Phospholipid ◽  
Phospholipid Metabolism ◽  
Internal Organs ◽  
New Biomarkers ◽  
First Time

Systemic sclerosis (SSc) is an autoimmune disease with fibrosis of the skin and/or internal organs, causing a decrease in quality of life and survival. There is no causative therapy, and the pathophysiology of the SSc remains unclear. Studies showed that lipid metabolism was relevant for autoimmune diseases, but little is known about the role of lipids in SSc. In the present study, we sought to explore the phospholipid profile of SSc by using the lipidomics approach. We also aimed to analyze lipidomics results for different clinical manifestations of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry for the lipidomic profiling of plasma samples from patients with SSc. Our study showed, for the first time, significant changes in the level of phospholipids such as plasmalogens and sphingomyelins from the plasma of SSc patients as compared to controls. Phosphatidylcholine plasmalogens species and sphingomyelins were significantly increased in SSc patients as compared to controls. Our results also demonstrated a significant association of changes in the metabolism of phospholipids (phosphatidylcholine and phosphatidylethanolamine plasmalogens species and sphingomyelins) with different clinical manifestations of SSc. Further lipidomic studies might lead to the detection of lipids as new biomarkers or therapeutic targets of SSc.

Immune system activation and fatigue during treadmill running: role of interferon

1998 ◽  
Vol 30 (6) ◽  
pp. 863-868 ◽  
Author(s):  
J. M. DAVIS ◽  
J. A. WEAVER ◽  
M. L. KOHUT ◽  
L. H. COLBERT ◽  
A. GHAFFAR ◽  
...  
Keyword(s):  
Immune System ◽  
Treadmill Running ◽  
Immune System Activation ◽  
System Activation

scholarly journals Perspectives on the Role of Photodynamic Therapy in the Treatment of Pancreatic Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Li ◽  
Qingyong Ma ◽  
Erxi Wu
Keyword(s):  
Pancreatic Cancer ◽  
Photodynamic Therapy ◽  
Experimental Studies ◽  
Oxygen Species ◽  
Tumor Cell Death ◽  
Antitumor Effects ◽  
Immune System Activation ◽  
System Activation ◽  
Photosensitizing Agent

Photodynamic therapy (PDT) is a noninvasive procedure involving a photosensitizing agent that is activated by light to produce reactive oxygen species (ROS) that selectively destroy tumor cells. In recent years, PDT has been used in the treatment of pancreatic cancer (PC). The antitumor effects of PDT include three main mechanisms: direct tumor cell death (necrosis, apoptosis, and autophagy), vascular destruction, and immune system activation. The present paper systematically summarizes the effects of PDT in the treatment of PC from the experimental studies to the clinical studies and discusses the mechanisms of PDT-induced PC destruction.

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 Toll-like receptors and damage-associated molecular patterns: novel links between inflammation and hypertension

2014 ◽  
Vol 306 (2) ◽  
pp. H184-H196 ◽  
Author(s):  
Cameron G. McCarthy ◽  
Styliani Goulopoulou ◽  
Camilla F. Wenceslau ◽  
Kathryn Spitler ◽  
Takayuki Matsumoto ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Cell Injury ◽  
Receptor Activation ◽  
Innate Immune ◽  
Immune System Activation ◽  
System Activation ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Low-grade systemic inflammation is a common manifestation of hypertension; however, the exact mechanisms that initiate this pathophysiological response, thereby contributing to further increases in blood pressure, are not well understood. Aberrant vascular inflammation and reactivity via activation of the innate immune system may be the first step in the pathogenesis of hypertension. One of the functions of the innate immune system is to recognize and respond to danger. Danger signals can arise from not only pathogenic stimuli but also endogenous molecules released following cell injury and/or death [damage-associated molecular patterns (DAMPs)]. In the short-term, activation of the innate immune system is beneficial in the vasculature by providing cytoprotective mechanisms and facilitating tissue repair following injury or infection. However, sustained or excessive immune system activation, such as in autoimmune diseases, may be deleterious and can lead to maladaptive, irreversible changes to vascular structure and function. An initial source of DAMPs that enter the circulation to activate the innate immune system could arise from modest elevations in peripheral vascular resistance. These stimuli could subsequently lead to ischemic- or pressure-induced events aggravating further cell injury and/or death, providing more DAMPs for innate immune system activation. This review will address and critically evaluate the current literature on the role of the innate immune system in hypertension pathogenesis. The role of Toll-like receptor activation on somatic cells of the vasculature in response to the release of DAMPs and the consequences of this activation on inflammation, vasoreactivity, and vascular remodeling will be specifically discussed.

Neopterin and kynurenine concentrations in aqueous humour of the anterior chamber of the eye and in serum of cataract patients with pseudoexfoliation

Pteridines ◽  
2000 ◽  
Vol 11 (3) ◽  
pp. 94-99 ◽  
Author(s):  
Guna Laganovska ◽  
Agris Martinsons ◽  
Bronislavs Pitrans ◽  
Bernhard Widner ◽  
Dietmar Fuchs
Keyword(s):  
Oxidative Stress ◽  
Immune System ◽  
Anterior Chamber ◽  
Aqueous Humour ◽  
Serum Concentrations ◽  
Selenium Content ◽  
Immune System Activation ◽  
System Activation ◽  
Cataract Patients

Summary In 40 cataract patients and in 51 patients without pseudoexfoliation (PES) we determined serum concentrations of neopterin, kynurenine, and selenium and concentrations of neopterin in aqueous humour from the anterior chamber of the eye. In addition, selenium content in lenses was determined. Significantly increased kynurenine and neopterin concentrations in serum and neopterin concentrations in aqueous humour were observed in mature cataract patients with PES compared to those without. These patients also presented with the lowest content of selenium in serum and lens, compared with cataract patients without PES. Increased concentrations of neopterin in serum and aqueous humour of the anterior chamber of eyes suggest an increased degree of oxidative stress in patients with PES. Thus, the results support the role of oxidative stress in the development of PES in cataract patients. The decreased content of selenium may elicit immune system activation via an increased oxidative stress as it is indicated by the increased formation of kynurenine and neopterin.

scholarly journals HHV-6A Infection and Systemic Sclerosis: Clues of a Possible Association

2019 ◽  
Vol 8 (1) ◽  
pp. 39
Author(s):  
Elisabetta Caselli ◽  
Irene Soffritti ◽  
Maria D’Accolti ◽  
Daria Bortolotti ◽  
Roberta Rizzo ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Plasma Levels ◽  
Human Herpesvirus ◽  
Infectious Agents ◽  
Internal Organs ◽  
Matrix Deposition ◽  
Skin Biopsies ◽  
Extracellular Matrix Deposition

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, excessive extracellular matrix deposition, and fibrosis of the skin and internal organs. Several infectious agents, including human herpesvirus-6 (HHV-6), have been suggested as possible triggering factors, but a direct association is still missing. We characterized 26 SSc patients for the presence of HHV-6 in tissues and blood, the anti-HHV-6 response, HLA-G plasma levels, and KIR typing. Given the prominent role of endothelial cells (EC) in SSc pathogenesis, along with HHV-6 tropism for EC, we also investigated the expression of pro-fibrosis factors in HHV-6 infected EC. Results showed the presence of HHV-6A in skin biopsies, and an increased virus load was associated with disease severity and poor natural killer (NK) response against the virus, particularly in subjects exhibiting a KIR2 phenotype. HLA-G plasma levels were significantly higher in HHV-6A/B-KIR2 positive SSc patients and in vitro HHV-6A infection-induced pro-fibrosis factors expression in EC, supporting its role in the development of the fibrosing process. Our data suggest an association between virus infection/reactivation and disease, opening the way to future studies to understand the mechanisms by which HHV-6A might contribute to the multifactorial pathogenesis of SSc.

scholarly journals The Role of Toll-Like Receptors in Oncotherapy

2019 ◽  
Vol 27 (8) ◽  
pp. 965-978 ◽  
Author(s):  
Caiqi Liu ◽  
Ci Han ◽  
Jinfeng Liu
Keyword(s):  
Anticancer Agents ◽  
Comprehensive Evaluation ◽  
Toll Like Receptors ◽  
Innate And Adaptive Immunity ◽  
Tlr Agonists ◽  
Immune System Activation ◽  
Potential Applications ◽  
Cancer Types ◽  
System Activation

Toll-like receptors (TLRs) are associated with tumor growth and immunosuppression, as well as apoptosis and immune system activation. TLRs can activate apoptosis and innate and adaptive immunity pathways, which can be pharmacologically targeted for the development of anticancer oncotherapies. Several studies and clinical trials indicate that TLR agonists are promising adjuvants or elements of novel therapies, particularly when used in conjunction with chemotherapy or radiotherapy. An increasing number of studies suggest that the activation of TLRs in various cancer types is related to oncotherapy; however, before this finding can be applied to clinical practice, additional studies are required. Research suggests that TLR agonists may have potential applications in cancer therapy; nevertheless, because TLR signaling can also promote tumorigenesis, a critical and comprehensive evaluation of TLR action is warranted. This review focuses on recent studies that have assessed the strengths and weaknesses of utilizing TLR agonists as potential anticancer agents.

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