The role of TNF‐α in the pathogenesis of inflammation and joint destruction in rheumatoid arthritis (RA): a study using a human RA/SCID mouse chimera

Background/Aim. Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods. Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results. Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significant difference in the histamine index which was increased proportionally with disease activity. Conclusion. Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.

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The Novel Role of MIF in the Secretion of IL-25, IL-31, and IL-33 from PBMC of Patients with Rheumatoid Arthritis

Molecules ◽

10.3390/molecules26164968 ◽

2021 ◽

Vol 26 (16) ◽

pp. 4968

Author(s):

Samuel García-Arellano ◽

Luis Alexis Hernández-Palma ◽

Sergio Cerpa-Cruz ◽

Gabriela Athziri Sánchez-Zuno ◽

Melva Guadalupe Herrera-Godina ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mononuclear Cells ◽

Joint Destruction ◽

Study Groups ◽

Joint Disease ◽

The Novel ◽

Peripheral Blood Mononuclear ◽

Cytokine Dysregulation ◽

New Evidence

Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease with complex pathogenesis associated with cytokine dysregulation. Macrophage migration inhibitory factor (MIF) plays a role in systemic inflammation and joint destruction in RA and could be associated with the secretion of other immune-modulatory cytokines such as IL-25, IL-31, and IL-33. For the above, our main aim was to evaluate the IL-25, IL-31, and IL-33 secretion from recombinant human MIF (rhMIF)-stimulated peripheral blood mononuclear cells (PBMC) of RA patients. The rhMIF and lipopolysaccharide (LPS) plus rhMIF stimuli promote the secretion of IL-25, IL-31, and IL-33 (p < 0.05) from PBMC of RA patients. The study groups, the different stimuli, and the interaction between both showed a statistically significant effect on the secretion of IL-25 (p < 0.05) and IL-31 (p < 0.01). The study of the effect of the RA patient treatments and their interaction with the effect of stimuli did not show an interaction between them. In conclusion, our study generates new evidence for the role of MIF in the secretion of IL-25, IL-31, and IL-33 and its immunomodulatory effect on RA.

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TNF-α Activating Osteoclasts in Patients with Psoriatic Arthritis Enhances the Recruitment of Osteoclast Precursors: A Plausible Role of WNT5A-MCP-1 in Osteoclast Engagement in Psoriatic Arthritis

International Journal of Molecular Sciences ◽

10.3390/ijms23020921 ◽

2022 ◽

Vol 23 (2) ◽

pp. 921

Author(s):

Shang-Hung Lin ◽

Ji-Chen Ho ◽

Sung-Chou Li ◽

Yu-Wen Cheng ◽

Chung-Yuan Hsu ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Rna Interference ◽

Joint Destruction ◽

Neutralizing Antibody ◽

Healthy Controls ◽

Osteoclast Precursors ◽

Tnf Α ◽

Wnt Ligands

Psoriatic arthritis (PsA) results from joint destruction by osteoclasts. The promising efficacy of TNF-α blockage indicates its important role in osteoclastogenesis of PsA. WNT ligands actively regulate osteoclastogenesis. We investigated how WNT ligands activate osteoclasts amid the TNF-α milieu in PsA. We first profiled the expression of WNT ligands in CD14+ monocyte-derived osteoclasts (MDOC) from five PsA patients and five healthy controls (HC) and then validated the candidate WNT ligands in 32 PsA patients and 16 HC. Through RNA interference against WNT ligands in MDOC, we determined the mechanisms by which TNF-α exerts its effects on osteclastogenesis or chemotaxis. WNT5A was selectively upregulated by TNF-α in MDOC from PsA patients. The number of CD68+WNT5A+ osteoclasts increased in PsA joints. CXCL1, CXCL16, and MCP-1 was selectively increased in supernatants of MDOC from PsA patients. RNA interference against WNT5A abolished the increased MCP-1 from MDOC and THP-1-cell-derived osteoclasts. The increased migration of osteoclast precursors (OCP) induced by supernatant from PsA MDOC was abolished by the MCP-1 neutralizing antibody. WNT5A and MCP-1 expressions were decreased in MDOC from PsA patients treated by biologics against TNF-α but not IL-17. We conclude that TNF-α recruits OCP by increased MCP-1 production but does not directly activate osteoclastogenesis in PsA.

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Multifaceted role of TNF-α during the pathogenesis of rheumatoid arthritis

Advances in Bioscience and Biotechnology ◽

10.4236/abb.2013.410123 ◽

2013 ◽

Vol 04 (10) ◽

pp. 937-940 ◽

Cited By ~ 2

Author(s):

Ramanjaneya V. R. Mula ◽

Rangaiah Shashidharamurthy

Keyword(s):

Rheumatoid Arthritis ◽

Tnf Α

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Number of individual ACPA reactivities in synovial fluid immune complexes, but not serum anti-CCP2 levels, associate with inflammation and joint destruction in rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-212627 ◽

2018 ◽

Vol 77 (9) ◽

pp. 1345-1353 ◽

Cited By ~ 6

Author(s):

Azita Sohrabian ◽

Linda Mathsson-Alm ◽

Monika Hansson ◽

Ann Knight ◽

Jörgen Lysholm ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Disease Activity ◽

Immune Complexes ◽

Magnetic Beads ◽

Joint Destruction ◽

Joint Pathology ◽

A New Technique ◽

Laboratory Measures

IntroductionIndividual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis.MethodsWe have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation.ResultsThe majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation.ConclusionsOur data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.

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CHANGES THE CYTOKINE PROFILE AND CALCIUM-REGULATING HORMONES IN RHEUMATOID ARTHRITIS

Russian Clinical Laboratory Diagnostics ◽

10.18821/0869-2084-2019-64-11-673-676 ◽

2019 ◽

Vol 64 (11) ◽

pp. 673-676

Author(s):

Asmaya Saftar Huseynova

Keyword(s):

Rheumatoid Arthritis ◽

Parathyroid Hormone ◽

Bone Loss ◽

Hypovitaminosis D ◽

Serum Levels ◽

Control Group ◽

Tnf Α ◽

High Production ◽

Serological Variant

The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.

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Pharmacokinetics-Based Chronoefficacy of Semen Strychni and Tripterygium Glycoside Tablet Against Rheumatoid Arthritis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.673263 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jingpan Lin ◽

Lu Gao ◽

Yanke Lin ◽

Shuai Wang ◽

Zemin Yang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Bone Destruction ◽

Systemic Exposure ◽

Inflammatory Factors ◽

Systemic Autoimmune Disease ◽

Active Ingredients ◽

Tnf Α ◽

Exposure Levels ◽

Semen Strychni

Rheumatoid arthritis is a systemic autoimmune disease characterized by synovial inflammation and bone destruction. Identifying drugs with time-varying efficacy and toxicity, and elucidating the mechanisms would help to improve treatment efficacy and reduce adverse effects. Here, we aimed to determine the chronoefficacy of semen strychni (SS) and tripterygium glycoside tablet (TGT) against rheumatoid arthritis in mice, and to investigate a potential role of circadian pharmacokinetics in generating chronoefficacy. SS extract and TGT suspension were prepared with ultrasonication. Effects of SS and TGT on collagen-induced arthritis (CIA) were evaluated by measuring TNF-α and IL-6 levels. SS dosed at ZT18 was more effective in protecting against CIA than drug dosed at ZT6 (i.e., lower levels of key inflammatory factors at ZT18 than at ZT6). This was accompanied by higher systemic exposure levels of strychnine and brucine (two main putative active ingredients of SS) in ZT18-treated than in ZT6-treated CIA mice. TGT dosing at ZT2 showed a better efficacy against CIA as compared to herb doing at ZT14. Consistently, ZT2 dosing generated a higher exposure of triptolide (a main putative active ingredient of TGT) as compared to ZT14 dosing in CIA mice. Moreover, strychnine, brucine, and triptolide significantly inhibited the proliferation of fibroblast-like synoviocytes, and reduced the production of TNF-α and IL-6 and the mRNAs of TNF-α, IL-6, COX-2, and iNOS, suggesting that they possessed an anti-arthritis activity. In conclusion, SS and TGT display chronoefficacy against rheumatoid arthritis in mice, that is attributed to circadian pharmacokinetics of main active ingredients. Our findings have implications for improving treatment outcomes of SS and TGT via timed delivery.

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Dysregulation of lncRNAs in Rheumatoid Arthritis: Biomarkers, Pathogenesis and Potential Therapeutic Targets

Frontiers in Pharmacology ◽

10.3389/fphar.2021.652751 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chenggui Miao ◽

Liangliang Bai ◽

Yaru Yang ◽

Jinling Huang

Keyword(s):

Rheumatoid Arthritis ◽

Epigenetic Modification ◽

Joint Destruction ◽

Research Progress ◽

Unknown Etiology ◽

Signal Pathways ◽

Cartilage Erosion ◽

Chronic Autoimmune Disease ◽

Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology, mainly manifested by persistent abnormal proliferation of fibroblast-like synoviocytes (FLSs), inflammation, synovial hyperplasia and cartilage erosion, accompanied by joint swelling and joint destruction. Abnormal expression or function of long noncoding RNAs (lncRNAs) are closely related to human diseases, including cancers, mental diseases, autoimmune diseases and others. The abnormal sequence and spatial structure of lncRNAs, the disorder expression and the abnormal interaction with the binding protein will lead to the change of gene expression in the way of epigenetic modification. Increasing evidence demonstrated that lncRNAs were involved in the activation of FLSs, which played a key role in the pathogenesis of RA. In this review, the research progress of lncRNAs in the pathogenesis of RA was systematically summarized, including the role of lncRNAs in the diagnosis of RA, the regulatory mechanism of lncRNAs in the pathogenesis of RA, and the intervention role of lncRNAs in the treatment of RA. Furthermore, the activated signal pathways, the role of DNA methylation and other mechanism have also been overview in this review.

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