TNF- α-elicited miR-29b potentiates resistance to apoptosis in peripheral blood monocytes from patients with rheumatoid arthritis

AbstractCD14-positive monocytes from patients with rheumatoid arthritis (RA) are more resistant to apoptosis, which promotes their persistence at the inflammatory site and thereby contributes crucially to immunopathology. We sought to elucidate one mechanism underlying this unique pathogenesis: resistance to apoptosis and the potential involvement of miR-29b in this process. CD14-positive peripheral blood monocytes (PBMs) from RA patients were observed to be resistant to spontaneous apoptosis compared to PBMs from healthy volunteers. Intriguingly, expression of miR-29b was significantly upregulated in PBMs from RA patients than those from healthy volunteers, and this upregulation was correlated with RA disease activity. Functionally, forced expression of the exogenous miR-29b in CD14-positive Ctrl PBMs conferred resistance to spontaneous apoptosis and Fas-induced death, thereafter enhancing the production of major proinflammatory cytokines in there cells. Following identification of the potential miR-29b target transcripts using bioinformatic algorithms, we showed that miR-29b could directly bind to the 3 ′-UTR of the high-mobility group box-containing protein 1 (HBP1) and inhibited its transcription in PBMs. Importantly, stable expression of the exogenous HBP1 in differentiated THP-1 monocytes effectively abolished miR-29b-elicited resistance to Fas-induced apoptosis. Finally, among patients with RA and good clinical responses to immunotherapy, expression levels of miR...
Source: Apoptosis - Category: Molecular Biology Source Type: research

Related Links:

CONCLUSIONS: irAEs are frequent in patients undergoing ICBT. Almost half of the patients that have irAEs require treatment. Musculoskeletal manifestations are not uncommon. PMID: 32896258 [PubMed - as supplied by publisher]
Source: Clinical and Experimental Rheumatology - Category: Rheumatology Tags: Clin Exp Rheumatol Source Type: research
We report that electrical stimulation (ES) stimulation of post-stroke aged rats led to an improved functional recovery of spatial long-term memory (T-maze), but not on the rotating pole or the inclined plane, both tests requiring complex sensorimotor skills. Surprisingly, ES had a detrimental effect on the asymmetric sensorimotor deficit. Histologically, there was a robust increase in the number of doublecortin-positive cells in the dentate gyrus and SVZ of the infarcted hemisphere and the presence of a considerable number of neurons expressing tubulin beta III in the infarcted area. Among the genes that were unique...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Current treatments for chronic immune-mediated diseases such as psoriasis, rheumatoid arthritis, or Crohn's disease commonly rely on cytokine neutralization using monoclonal antibodies; however, such approaches have drawbacks. Frequent repeated dosing can lead to the formation of anti-drug antibodies and patient compliance issues, and it is difficult to identify a single antibody that is broadly efficacious across diverse patient populations. As an alternative to monoclonal antibody therapy, anti-cytokine immunization is a potential means for long-term therapeutic control of chronic inflammatory diseases. Here we report a ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Abstract Although most autoimmune diseases are considered to be CD4 T-cell or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab, oblinutuzumab, ofatumumab that are used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities, and ocrelizumab in multiple sclerosis. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of autoimmunity and COVID-19, it was...
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research
Authors: Alahdal M, Duan L, Ouyang H, Wang D Abstract Osteoarthritis (OA) is a chronic degenerative joint disease and a leading cause of disability. It involves articular cartilage destruction and a whole joint inflammation. In spite of OA pathogenesis is still unclear, new studies on the OA pathophysiological aetiology and immunomodulation therapy continuously achieve significant advances with new concepts. Here, we focus on the indoleamine-2,3-dioxygenase1 (IDO1) activity in the osteoarthritis (OA), which is one of the noticeable enzymes in the synovial fluid of arthritis patients. It was recognized as an essenti...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
Toll-Like Receptor 4 (TLR4) is one of the receptors of innate immunity. It is activated by Pathogen- and Damage-Associated Molecular Patterns (PAMPs and DAMPs) and triggers pro-inflammatory responses that belong to the repertoire of innate immune responses, consequently protecting against infectious challenges and boosting adaptive immunity. Mild TLR4 stimulation by non-toxic molecules resembling its natural agonist (lipid A) provided efficient vaccine adjuvants. The non-toxic TLR4 agonist monophosphoryl lipid A (MPLA) has been approved for clinical use. This suggests the development of other TLR4 agonists as adjuvants or ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Immunotherapy, Ahead of Print.
Source: Immunotherapy - Category: Allergy & Immunology Authors: Source Type: research
Management of rheumatoid arthritis (RA) in patients with cancer is complex and requires a multidisciplinary approach. A few studies have examined the risk for recurrence in patients with RA receiving disease-modifying antirheumatic drugs, primarily tumor necrosis factor- α inhibitors. Although these agents seem to be safe in patients with a history of cancer and no evidence of disease, additional information is needed to determine their potential effects in patients with RA and active cancer. Patients with RA undergoing cancer therapy, including surgery, radiation, chemotherapy, and immunotherapy, need to be carefull...
Source: Rheumatic Disease Clinics of North America - Category: Rheumatology Authors: Source Type: research
AbstractImmunotherapies are often used for the treatment, remission, and possible cure of autoimmune diseases, infectious diseases, and cancers. Empirical evidence illustrates that females and males differ in outcomes following the use of biologics for the treatment of autoimmune diseases, e.g., rheumatoid arthritis (RA), infectious diseases, e.g., influenza, and solid tumor cancers. Females tend to experience more adverse reactions than males following the use of a class of biologics referred to as immunotherapies. For immunotherapies aimed at stimulating an immune response, e.g., influenza vaccines, females develop great...
Source: Biology of Sex Differences - Category: Biology Source Type: research
Radiopharmaceutical developer Navidea Biopharmaceuticals has inked a letter...Read more on AuntMinnie.comRelated Reading: Navidea gets 5-year patent extension for Lymphoseek Navidea raises $7.6M, regains listing compliance Navidea claims victories in legal case with former CEO Navidea signs immunotherapy deal with IMV Navidea highlights rheumatoid arthritis results
Source: AuntMinnie.com Headlines - Category: Radiology Source Type: news
More News: Actemra | Arthritis | Immunotherapy | Molecular Biology | Remicade | Rheumatoid Arthritis | Rheumatology