Dataset Information

Increased FURIN expression in rheumatoid arthritis patients and its anti-inflammatory effect.

ABSTRACT:

Background

FURIN belongs to the proprotein convertase family that processes proproteins and is involved in many diseases. However, the role of FURIN in rheumatoid arthritis (RA) remains unknown. In this study, we investigated the association between circulating FURIN and disease activity in patients with RA and the effect of FURIN in THP-1-derived macrophages.

Methods

A total of 108 RA patients and 39 healthy controls participants were included in this study. RA patients were divided into four disease activity groups determined by the Disease Activity Score of 28 joints (DAS28). FURIN expression in peripheral blood mononuclear cells (PBMCs) and serum was detected by using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Western blotting and qRT-PCR were used to detect cytokines level after interfering FURIN expressed in THP-1-derived macrophages.

Results

Both FURIN mRNA and protein levels were significantly higher in RA patients than in healthy controls participants (P < .001). No significant difference in FURIN expression was observed among the four RA groups (P > .05). Spearman correlation revealed that FURIN positively correlated with transforming growth factor-?1(TGF-?1), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP). Moreover, the inhibition of FURIN in THP-1-derived macrophages promoted the caspase-1 and IL-1? expression (P < .05).

Conclusion

FURIN levels were significantly increased in the peripheral blood of RA patients and were not associated with disease activity. The inhibition of FURIN in THP-1-derived macrophages with elevated IL-1? levels shows that FURIN may have an anti-inflammatory effect.

SUBMITTER: Cao R

PROVIDER: S-EPMC7755791 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Increased FURIN expression in rheumatoid arthritis patients and its anti-inflammatory effect.

Cao Rong R Zhang Ying Y Du Juping J Chen Shuaishuai S Wang Na N Ying Haijian H Shen Bo B

Journal of clinical laboratory analysis 20200825 12

<h4>Background</h4>FURIN belongs to the proprotein convertase family that processes proproteins and is involved in many diseases. However, the role of FURIN in rheumatoid arthritis (RA) remains unknown. In this study, we investigated the association between circulating FURIN and disease activity in patients with RA and the effect of FURIN in THP-1-derived macrophages.<h4>Methods</h4>A total of 108 RA patients and 39 healthy controls participants were included in this study. RA patients were divi ...[more]

PMID: 32840921

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Project description:Background:Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects synovial joints, leading to inflammation, joint destruction, loss of function, and disability. Although recent pharmaceutical advances have improved treatment of RA, patients with RA often inquire about dietary interventions to improve RA symptoms, as they perceive rapid changes in their symptoms after consumption of certain foods. There is evidence that some ingredients have pro- or anti-inflammatory effects. In addition, recent literature has shown a link between diet and microbiome changes. Both diet and the gut microbiome are linked to circulating metabolites that may modulate inflammation. However, evidence of the effects of an anti-inflammatory and probiotic-rich diet in patients with RA is scarce. There is also a need for biological data to support its anti-inflammatory effects. Methods:The main goal of this study is to delineate the design process for a diet tailored to our RA population. To achieve this goal, we collected information on diet, supplements, cooking methods, and intake of different ingredients for each patient. Different groups were interviewed, and their feedback was assessed to design a diet that incorporates suggested anti-inflammatory ingredients in a manner that was easy for patients to adopt based on their lifestyles and backgrounds. Results:We designed a diet that includes a high intake of potential anti-inflammatory ingredients. Feedback from highly motivated patients was critical in constructing an anti-inflammatory diet (ITIS diet) with elevated adherence. Conclusion:In order to tailor our diet, we surveyed our patients on several different parameters. We obtained important feedback on how feasible our ITIS diet is for RA patients. Using this feedback, we made minor improvements and finalized the design of the ITIS diet. This diet is being used in an on-going pilot study to determine their anti-inflammatory effect in pain and joint swelling in RA patients. Trial registration:Not applicable.

Project description:Periodontitis, a bacterial-induced infection of the supporting soft and hard tissues of the teeth (the periodontium), is common in patients with rheumatoid arthritis (RA). As RA and periodontitis underlie common inflammatory pathways, targeting the progression of RA might mediate both periodontitis and RA. On the other hand, patients with RA on immunosuppressive medication have an increased risk of infection. Therefore, the objective of this longitudinal observation study was to assess the effect of methotrexate (MTX) and anti-tumor necrosis factor-α (anti-TNF, etanercept) treatment on the periodontal condition of RA patients. Overall, 14 dentate treatment-naive RA patients starting with MTX and 12 dentate RA patients starting with anti-TNF therapy in addition to MTX were included. Follow-up was scheduled matching the routine protocol for the respective treatments. Prior to the anti-rheumatic treatment with MTX or the anti-TNF therapy in addition to MTX, and during follow-up, i.e., 2 months for MTX, and 3 and 6 months for the anti-TNF therapy in addition to MTX, the periodontal inflamed surface area (PISA) was measured. The efficacy of the anti-rheumatic treatment was assessed by determining the change in RA disease activity (DAS28-ESR). Furthermore, the erythrocyte sedimentation rates were determined and the levels of C-reactive protein, IgM-rheumatoid factor, anti-cyclic citrullinated protein antibodies, and antibodies to the periodontal pathogen Porphyromonas gingivalis, were measured. Subgingival sampling and microbiological characterization of the subgingival microflora was done at baseline. MTX or anti-TNF treatment did not result in an improvement of the periodontal condition, while both treatments significantly improved DAS28 scores (both p < 0.01), and reduced C-reactive protein levels and erythrocyte sedimentation rates (both p < 0.05). It is concluded that anti-rheumatic treatment (MTX and anti-TNF) has negligible influence on the periodontal condition of RA patients.

Project description:BACKGROUND:Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects 0.5-1.0% of the population, and where many patients in spite of modern pharmacological treatment fail to reach remission. This affects physical as well as mental wellbeing and leads to severely reduced quality of life and reduced work capacity, thus yielding high individual as well as societal costs. As a complement to modern pharmacological treatment, lifestyle intervention should be evaluated as a treatment option. Scientific evidence exists for anti-inflammatory effects by single foods on RA, but no study exists where these foods have been combined to obtain maximum effect and thus offer a substantial improvement in patient life quality. The main goal of the randomized cross-over trial ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis) is to test the hypothesis that an anti-inflammatory diet intervention, compared to a regular diet, will decrease disease activity and improve quality of life in patients with stable established RA. METHODS:In total, 50 RA patients with moderate disease activity are randomized to receive initially either a portfolio diet based on several food items with suggested anti-inflammatory effects or a control diet during 2?×?10 weeks with 3 months wash-out between diets. Food bags are delivered weekly by a home food delivery chain and referred to as the fiber bag and the protein bag, respectively, to partially blind participants. Both groups continue with regular pharmacological treatment. Known food biomarkers will be analyzed to measure intervention compliance. Impact on disease severity (measured by DAS28, a composite score which predicts disability and progression of RA), risk markers for cardiovascular disease and quality of life are evaluated after each diet regimen. Metabolomics will be used to evaluate the potential to predict responders to dietary treatment. A health economic evaluation is also included. DISCUSSION:The nutritional status of patients with RA often is poor and many ask their physician for diet advice. No evidence-based dietary guidelines for patients with RA exist because of the paucity of well-conducted sufficiently large diet intervention trials. ADIRA is an efficacy study and will provide evidence as to whether dietary treatment of RA can reduce disease activity and improve quality of life as well as reduce individual and societal costs. TRIAL REGISTRATION:ClinicalTrials.gov Registration Number: NCT02941055 .

Dataset Information

Increased FURIN expression in rheumatoid arthritis patients and its anti-inflammatory effect.

Background

Methods

Results

Conclusion

Publications

Increased FURIN expression in rheumatoid arthritis patients and its anti-inflammatory effect.

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