scholarly journals Enhanced stability of tristetraprolin mRNA protects mice against immune-mediated inflammatory pathologies

2016 ◽  
Vol 113 (7) ◽  
pp. 1865-1870 ◽  
Author(s):  
Sonika Patial ◽  
Alan D. Curtis ◽  
Wi S. Lai ◽  
Deborah J. Stumpo ◽  
Georgette D. Hill ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Genetic Locus ◽  
The Body ◽  
Cultured Fibroblasts ◽  
Proinflammatory Mediators ◽  
Immune Mediated ◽  
Mouse Tissues ◽  
Attractive Therapeutic Target ◽  
Specific Mrnas ◽  
Mrna Binding

Tristetraprolin (TTP) is an inducible, tandem zinc-finger mRNA binding protein that binds to adenylate-uridylate–rich elements (AREs) in the 3′-untranslated regions (3′UTRs) of specific mRNAs, such as that encoding TNF, and increases their rates of deadenylation and turnover. Stabilization of Tnf mRNA and other cytokine transcripts in TTP-deficient mice results in the development of a profound, chronic inflammatory syndrome characterized by polyarticular arthritis, dermatitis, myeloid hyperplasia, and autoimmunity. To address the hypothesis that increasing endogenous levels of TTP in an intact animal might be beneficial in the treatment of inflammatory diseases, we generated a mouse model (TTPΔARE) in which a 136-base instability motif in the 3′UTR of TTP mRNA was deleted in the endogenous genetic locus. These mice appeared normal, but cultured fibroblasts and macrophages derived from them exhibited increased stability of the otherwise highly labile TTP mRNA. This resulted in increased TTP protein expression in LPS-stimulated macrophages and increased levels of TTP protein in mouse tissues. TTPΔARE mice were protected from collagen antibody-induced arthritis, exhibited significantly reduced inflammation in imiquimod-induced dermatitis, and were resistant to induction of experimental autoimmune encephalomyelitis, presumably by dampening the excessive production of proinflammatory mediators in all cases. These data suggest that increased systemic levels of TTP, secondary to increased stability of its mRNA throughout the body, can be protective against inflammatory disease in certain models and might be viewed as an attractive therapeutic target for the treatment of human inflammatory diseases.

scholarly journals Gut Microbiome and Organ Fibrosis

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 352
Author(s):  
Carolina F. F. A. Costa ◽  
Benedita Sampaio-Maia ◽  
Ricardo Araujo ◽  
Diana S. Nascimento ◽  
Joana Ferreira-Gomes ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Inflammatory Diseases ◽  
Adaptive Immune System ◽  
Organ Damage ◽  
Pathological Process ◽  
The Body ◽  
Intestinal Fibrosis ◽  
Immune Mediated ◽  
Major Player ◽  
Organ Fibrosis

Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.

Mechanisms and practical use of the bactericidal effects of ozone and ozonated oils

2020 ◽  
pp. 45-52
Author(s):  
S. Schetinin
Keyword(s):  
Inflammatory Diseases ◽  
Aerobic Metabolism ◽  
Active Oxygen ◽  
The Body ◽  
Bactericidal Action ◽  
Ozone Therapy ◽  
Energy Substrates ◽  
Bactericidal Effects ◽  
Viral Nature

The analysis of the clinical and immunological effectiveness of ozone therapy is carried out. The mechanism of the bactericidal action of ozone in the treatment of infectious and inflammatory diseases of a bacterial and viral nature is analyzed. Ozonation of oils leads to the formation of a complex and heterogeneous cascade of components. Ozonides provide the body with some prolonged supply of active oxygen to maintain aerobic metabolism and the required level of energy substrates.

Molecular Targets of Phytochemicals for Skin Inflammation

2018 ◽  
Vol 24 (14) ◽  
pp. 1533-1550 ◽  
Author(s):  
Jong-Eun Kim ◽  
Ki Won Lee
Keyword(s):  
Skin Diseases ◽  
Molecular Targets ◽  
Skin Inflammation ◽  
Mechanisms Of Action ◽  
The Body ◽  
Cellular Damage ◽  
Aesthetic Appearance ◽  
Immune Mediated ◽  
Skin Conditions ◽  
Effects Of Aging

Skin is a protective organ and the largest of the human body. Due to its pivotal role in aesthetic appearance, skin health has a significant impact on quality of life. Chronic inflammation of the skin often marks the beginning of various skin diseases. Immune-mediated responses serve to protect the body from external insults and require succinct control, and can lead to ongoing cellular damage and various skin conditions if left unchecked. Studies have shown that phytochemicals can alter processes involved in skin inflammation and alleviate the effects of aging, cancer, atopic dermatitis, psoriasis, and vitiligo. Direct molecular targets of some phytochemicals have been identified and their precise mechanisms of action investigated. In this review, we summarize recent findings on the effects of phytochemicals on skin inflammation and the mechanisms of action involved.

scholarly journals 4CPS-329 Do patients with immune mediated inflammatory diseases think they know their medication?

2021 ◽  
Author(s):  
A Melgarejo-Ortuño ◽  
RM Romero Jiménez ◽  
E Chamorro De Vega ◽  
A Ais Larisgoitia ◽  
ME Lobato Matilla ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Immune Mediated

scholarly journals POS1180 TREATMENT COMPLIANCE OF PATIENTS WITH RHEUMATOID ARTHRITIS DURING THE FIRST WAVE OF THE SARS-CoV-2/COVID-19 PANDEMIC IN PORTUGAL: RESULTS FROM THE COVID IN RA (COVIDRA) SURVEY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 871.2-871
Author(s):  
F. Araujo ◽  
N. Gonçalves ◽  
A. F. Mourão
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Immunosuppressive Treatment ◽  
Treatment Compliance ◽  
Web Based ◽  
Symptoms Of Depression ◽  
Immune Mediated ◽  
Attending Physician ◽  
The Impact ◽  
E Mail

Background:The outcomes of the infection by the SARS-CoV-2 in patients with immune-mediated inflammatory diseases were largely unknown during the early days of the COVID-19 pandemic. It was hypothesized that these patients were at higher risk of morbidity and mortality due to their inherent immune dysfunction and immunosuppressive therapy. Several rheumatology societies issued recommendations urging patients not to stop their anti-rheumatic treatments.Objectives:To assess treatment compliance of patients with rheumatoid arthritis (RA) during the first wave of the SARS-CoV-2/COVID-19 pandemic in Portugal.Methods:The web-based survey COVIDRA (COVID in RA) was developed to assess the impact of the first wave mandatory confinement in patients with RA focusing on 5 domains: RA symptoms, attitudes towards medication, employment status, physical exercise and mental health. The questionnaire was sent to RA patients through e-mail and social media of the Portuguese Society of Rheumatology and two patient associations; and it was filled locally at two rheumatology centers in Lisbon. Recruitment took place during June and July 2020. Descriptive statistics were generated by the survey software and were afterwards transported and evaluated using appropriate biostatistics software.Results:We obtained 441 valid questionnaires. Most respondents were female (88.4%), caucasian (93.6%), with a mean age of 58 (+/-13) years. The majority (57.6%) had longstanding disease (>10 years) and were treated with csDMARDs (63.2%) and/or bDMARDs/tsDMARDS (23,7%). Only 14% (N=61) discontinued or reduced the dosage or frequency of their RA treatment. Most of these changes were previously planned by the attending physician (27.9%). Only 11 patients (18%) discontinued their immunosuppressive medication out of fear of becoming infected with SARS-CoV-2 (corresponding to 2.5% of total responders). Another 11 patients did so because they had no prescription, couldn’t go to the community/hospital pharmacy or couldn’t afford the medication. Although these numbers preclude any statistical analysis, when compared to patients who persisted on their treatment, those discontinuing due to fear of contagion were younger (56.4 vs 58.5 years), all female (100 vs 86.8%), with long-lasting disease (≥ 11 years) (90.9% vs 57.5%), more frequently treated with bDMARDs (36.4 vs 23.1%) and presenting more symptoms of depression (54.5 vs 49.7%).Conclusion:Most RA patients complied with their treatment during the first wave of the SARS-CoV-2 pandemic in Portugal. Only a minority changed their immunosuppressive treatment due to fear of SARS-CoV-2 infection. Very similar rates of immunosuppressive discontinuation due to fear of contagion were reported by other authors (such as Schmeiser et al, Pineda-sic et al and Fragoulis et al).Disclosure of Interests:Filipe Araujo Speakers bureau: Pfizer, Biogen, Novartis, Menarini, Consultant of: MSD, Nuno Gonçalves: None declared, Ana Filipa Mourão: None declared.

scholarly journals The Potential of OMICs Technologies for the Treatment of Immune-Mediated Inflammatory Diseases

2021 ◽  
Vol 22 (14) ◽  
pp. 7506
Author(s):  
Charles Gwellem Anchang ◽  
Cong Xu ◽  
Maria Gabriella Raimondo ◽  
Raja Atreya ◽  
Andreas Maier ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Standard Of Care ◽  
Incidence Rates ◽  
Irreversible Damage ◽  
Omics Technologies ◽  
Progressive Development ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Affected Tissue ◽  
Systemic Nature

Immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel diseases and inflammatory arthritis (e.g., rheumatoid arthritis, psoriatic arthritis), are marked by increasing worldwide incidence rates. Apart from irreversible damage of the affected tissue, the systemic nature of these diseases heightens the incidence of cardiovascular insults and colitis-associated neoplasia. Only 40–60% of patients respond to currently used standard-of-care immunotherapies. In addition to this limited long-term effectiveness, all current therapies have to be given on a lifelong basis as they are unable to specifically reprogram the inflammatory process and thus achieve a true cure of the disease. On the other hand, the development of various OMICs technologies is considered as “the great hope” for improving the treatment of IMIDs. This review sheds light on the progressive development and the numerous approaches from basic science that gradually lead to the transfer from “bench to bedside” and the implementation into general patient care procedures.

Sign in / Sign up

Export Citation Format

Share Document