scholarly journals A Polymorphism ofORAI1rs7135617, Is Associated with Susceptibility to Rheumatoid Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Jeng-Hsien Yen ◽  
Che-Mai Chang ◽  
Yu-Wen Hsu ◽  
Chih-Hung Lee ◽  
Mei-Shin Wu ◽  
...  

Rheumatoid arthritis (RA), a chronic inflammatory disease usually occurring in synovial tissues and joints, is highly associated with genetic and environmental factors.ORAI1, a gene related to cellular immune system, has been shown to be involved in the pathogenesis of chronic inflammatory diseases and immune diseases. To identify whetherORAI1gene contributes to RA susceptibility, we enrolled 400 patients with RA and 621 healthy individuals for a case-control genetic association study. Five tagging single nucleotides polymorphisms (tSPNs) withinORAI1gene were selected for genotyping. An SNP, rs7135617, showed a significant correlation with the risk of RA. Our results indicated that genetic polymorphism ofORAI1gene is involved in the susceptibility of RA in a Taiwanese population.

2019 ◽  
Vol 217 (1) ◽  
Author(s):  
Pascale Zwicky ◽  
Susanne Unger ◽  
Burkhard Becher

Chronic inflammatory diseases like psoriasis, Crohn’s disease (CD), multiple sclerosis (MS), rheumatoid arthritis (RA), and others are increasingly recognized as disease entities, where dysregulated cytokines contribute substantially to tissue-specific inflammation. A dysregulation in the IL-23/IL-17 axis can lead to inflammation of barrier tissues, whereas its role in internal organ inflammation remains less clear. Here we discuss the most recent developments in targeting IL-17 for the treatment of chronic inflammation in preclinical models and in patients afflicted with chronic inflammatory diseases.


Author(s):  
K. Lyngberg ◽  
N. Tvede ◽  
J. Halkjaer-Kristensen ◽  
V. Andersen ◽  
B. K. Pedersen

2021 ◽  
Author(s):  
Ilya Korsunsky ◽  
Kevin Wei ◽  
Mathilde Pohin ◽  
Edy Y. Kim ◽  
Francesca Barone ◽  
...  

SummaryPro-inflammatory fibroblasts are critical to pathogenesis in rheumatoid arthritis, inflammatory bowel disease, interstitial lung disease, and Sjögren’s syndrome, and represent a novel therapeutic target for chronic inflammatory disease. However, the heterogeneity of fibroblast phenotypes, exacerbated by the lack of a common cross-tissue taxonomy, has limited the understanding of which pathways are shared by multiple diseases. To investigate, we profiled patient-derived fibroblasts from inflamed and non-inflamed synovium, intestine, lung, and salivary glands with single-cell RNA-sequencing. We integrated all fibroblasts into a multi-tissue atlas to characterize shared and tissue-specific phenotypes. Two shared clusters, CXCL10+CCL19+ immune-interacting and SPARC+COL3A1+ vascular-interacting fibroblasts were expanded in all inflamed tissues and additionally mapped to dermal analogues in a public atopic dermatitis atlas. We further confirmed these human pro-inflammatory fibroblasts in animal models of lung, joint, and intestinal inflammation. This work represents the first cross-tissue, single-cell fibroblast atlas revealing shared pathogenic activation states across four chronic inflammatory diseases.


Author(s):  
Jie Jack Li

Inflammation and immunity, like all other normal reactions of the body, are meant to preserve or restore health. They can nonetheless cause a range of uncomfortable symptoms. Inflammation is such a complicated process that one would have a hard time reaching a consensus on its definition. Historically, inflammation was one of the earliest recognized and defined diseases. Two thousand years ago, Roman physician and encyclopedist Aulus Cornelius Celsus (25 B.C.–50 A.D., not to be confused with Celsius, the unit for temperature) described the four cardinal signs of inflammation: calor (warmth), dolor (pain), tumor (swelling), and rubor (redness). The fifth element of inflammation, functio laesi (loss of function or movement), was noted later. Classic inflammatory diseases include rheumatoid arthritis and Crohn’s disease, an inflammatory bowel disease. However, evidence is mounting that inflammation is implicated in many diseases that are not normally considered inflammatory. For instance, when arterial plaques become inflamed they can burst open, prompting a myriad of heart diseases. Inflammatory bowel conditions greatly increase the risk of colon tumors. Even diabetes has been associated with a number of inflammatory compounds. It was hard to define what inflammation was, but finding a remedy was even more challenging. Aspirin, available in 1880, represented possibly the first really effective treatment for inflammation, whereas cortisone and other corticosteroids were not available for the treatment of rheumatoid arthritis until the early 1950s. Louis Pasteur stated, “Dans les champs de l’observation, le hazard ne favorise que les esprit préparés” [In the field of experimentation, chance favors the prepared mind]. Like numerous cases in drug discovery, Philip S. Hench’s discovery of cortisone for the treatment of rheumatoid arthritis illustrates Pasteur’s point. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by pain, swelling, and subsequent destruction of joints. Until the late 1940s, there was no viable treatment, and, understandably, pessimism prevailed in medical society about its prognosis. Even William Osler, one of the greatest physicians, said “When an arthritic patient walks in the front door, I want to run out the back door!” The situation did not change much until Hench discovered a “miracle drug” in 1949.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Bingrui Li ◽  
Nianyu Li ◽  
Le Zhang ◽  
Kai Li ◽  
Yingtian Xie ◽  
...  

Background. circRNAs are part of the competitive endogenous RNA network, which putatively function as miRNA sponges and play a crucial role in the development of numerous diseases. However, studies of circRNAs in rheumatoid arthritis (RA) disease are limited. This work aims to identify the expression pattern of circRNAs in synovial tissues and their inflammatory regulation mechanism. Methods. We first compared the mRNA expression in rheumatoid arthritis patients with that in healthy volunteers by GEO database mining to identify gene loci specifically expressed in synovial tissues. Functional enrichment algorithms were then used to draw the interactome diagram of circRNAs-miRNAs-mRNAs. Finally, loss-of-function and rescue assays of the candidate circRNAs were performed in vitro. Results. A total of 29 differentially expressed circRNAs related to rheumatoid arthritis were discovered. Silencing of hsa_circ_0001859 suppressed ATF2 expression and decreased inflammatory activity in SW982 cells. Hsa_circ_0001859 could compete with ATF2 for miR-204/211. Discussion. These findings indicate that hsa_circ_0001859 participates deeply in the process of chronic inflammatory disease in synovial tissue.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ying-Jie Chen ◽  
Yu-Xi Liu ◽  
Jia-Ying Wu ◽  
Chun-Yu Li ◽  
Min-Min Tang ◽  
...  

AbstractFibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE’s anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug.


2016 ◽  
Vol 40 (6) ◽  
Author(s):  
Abbas-Ali Fallah ◽  
Saeid Morovvati ◽  
Kazem Ahmadi ◽  
Gholam Hossein Alishiri ◽  
Mahdi Fasihi-Ramandi

AbstractBackground:Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by angiogenesis, cell proliferation and bone and cartilage damage in the affected joint. Many genetic and environmental factors contribute to RA susceptibility.Methods:Iranian patients with confirmed RA, aged over 50 years, were compared with healthy controls for allelic and genotypic frequencies of these polymorphisms. The subjects and controls were matched through their race, age and sex. After whole genome extraction, we compared genotype frequencies of analyzed alleles in RA patients and controls using a polymerase chain reaction (PCR)-restriction fragment length polymorphism assay. Association ofResults:Statistical analysis indicated no association between RA andConclusions:This study did not find any association between RA and


2020 ◽  
Vol 118 (1) ◽  
pp. e2017120118
Author(s):  
Paula B. Donate ◽  
Kalil Alves de Lima ◽  
Raphael S. Peres ◽  
Fausto Almeida ◽  
Sandra Y. Fukada ◽  
...  

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint destruction and severe morbidity. Cigarette smoking (CS) can exacerbate the incidence and severity of RA. Although Th17 cells and the Aryl hydrocarbon receptor (AhR) have been implicated, the mechanism by which CS induces RA development remains unclear. Here, using transcriptomic analysis, we show thatmicroRNA-132is specifically induced in Th17 cells in the presence of either AhR agonist or CS-enriched medium.miRNA-132thus induced is packaged into extracellular vesicles produced by Th17 and acts as a proinflammatory mediator increasing osteoclastogenesis through the down-regulation of COX2. In vivo, articular knockdown ofmiR-132in murine arthritis models reduces the number of osteoclasts in the joints. Clinically, RA patients express higher levels ofmiR-132than do healthy individuals. This increase is further elevated by cigarette smoking. Together, these results reveal a hitherto unrecognized mechanism by which CS could exacerbate RA and further advance understanding of the impact of environmental factors on the pathogenesis of chronic inflammatory diseases.


2020 ◽  
Vol 16 (4) ◽  
Author(s):  
G.T. Tongshuwar ◽  
A.O. Ojetunde ◽  
A.F. Oyegoke ◽  
T. Oyegoke

Relevance. Rheumatoid arthritis (RA) is an autoimmune disorder leading to the inflammation of the joints. This inflammation finds expression in the lining of the synovial tissues causing swellings and severe pains and deterioration of the bone in the long run. This disease's exact etiology is not yet to be ascertained; however, there are claims of the interplay of genetic and environmental factors. RA is one of the diseases ravaging the people of Jos in Nigeria, owing to the high cost of orthodox medicine. Objective. The study was carried out to collect information and find out plants used to treat rheumatoid arthritis in Jos, Nigeria, in addition to the availability of the plant(s). Materials and methods. An electronic-based questionnaire was used to get information from the respondents. Result. Eight species of plants were reported to be used. Garlic (Allium sativum), Ginger (Zingiber officinale), Turmeric (Curcuma longa), and Onion (Allium cepa) were the dominant plants reportedly used. The parts of plants used are the plant bulb and stem. They are reported to be prepared by grinding and herbal mixture; chewing and decoction were not popular. Respondents with this information reported their willingness to share with both family and friends. Conclusion. This study shows the availability of traditional RA treatment and the preservation of verbal form knowledge.


Pteridines ◽  
2004 ◽  
Vol 15 (3) ◽  
pp. 107-112 ◽  
Author(s):  
Georg Hoffmann ◽  
Wolfgang Schobersberger

Abstract In this review, we will summarize our investigations on the potential biochemical, physiological, and pathophysiological effects of neopterin in the course of infection and inflammation. In a number of in v/'iro-studies wc could show that the pteridine compound neopterin manifested distinct biochemical properties via interfering with cellular redox mechanisms. Among the observed actions of neopterin are the stimulation of inducible nitric oxide synthase gene expression and nitric oxide release, the activation of the transcription factor nuclear factor-κΒ, the induction of apoptotic ccll death, the inhibition of erythropoietin synthesis and release, and the stimulation of tumor necrosis factor-α generation in different cell culture as well as organic models. By these means, neopterin may represent a part of the host-defence reactions. In addition, an excessive or continous release of neopterin due to a chronically activated cellular immune system may contribute to the deleterious events commonly observed in progressive infectious or inflammatory diseases. Our data are supported by the findings of a strong correlation between raised levels of neopterin and the severity and the outcome of these disorders.


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