scholarly journals Target effector role of vascular endothelium in the inflammatory response: insights from the clinical trial of anti-TNF alpha antibody in rheumatoid arthritis.

1997 ◽  
Vol 50 (5) ◽  
pp. 225-233 ◽  
Author(s):  
E Paleolog
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trial ◽  
Inflammatory Response ◽  
Vascular Endothelium ◽  
Tnf Alpha

scholarly journals Inflammatory response in rheumatoid arthritis

2004 ◽  
Vol 23 (4) ◽  
pp. 375-380 ◽  
Author(s):  
Ljiljana Petrovic-Rackov ◽  
Nada Pejnovic ◽  
Zoran Mijuskovic ◽  
Gordana Ercegovic
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Inflammatory Response ◽  
Tnf Alpha ◽  
C Reactive Protein ◽  
General Activity ◽  
Reactive Protein ◽  
High Degree ◽  
Active Disease

The aim of the research is to determine the clinical significance of cytokines TNF-alpha, IL-12, IL-15 and IL-18 in evaluation of the activity of rheumatoid arthritis (RA). By comparing the concentrations in 30 patients with high, 14 patients with moderate and 20 patients with mild activity of RA it is established that the patients with high degree of disease activity, have significantly high (p<0.01; p<0.05) concentrations of examined cytokines and rheumatoid factor in blood and synovial fluid as well as C-reactive protein in serum in relation to patients with moderate and mild active disease. We have concluded that the cytokines concentrations can be good indicators of the degree of the general activity of RA. This research can contribute to interpretation of insufficiently well known views of pathogenesis role of cytokines in active disease.

scholarly journals Primary pathologic role of interleukin-6 in rheumatoid arthritis

2013 ◽  
pp. 40-46
Author(s):  
G.L. Bajocchi ◽  
N. Pipitone ◽  
P.L. Boiardi ◽  
C. Salvarani
Keyword(s):  
Rheumatoid Arthritis ◽  
Interleukin 6 ◽  
Cultured Cells ◽  
Inflammatory Diseases ◽  
Acute Phase Reactant ◽  
Therapeutic Benefit ◽  
Phase Iii ◽  
Tnf Alpha ◽  
Proinflammatory Activity

BACKGROUND Interleukin-6 (IL-6) is a polyfunctional cytokine that regulates a very large number of cellular activities. Its implication in acute-phase reactant production by hepatocytes is of particular interest, as is its involvement in chronic inflammatory diseases, mainly rheumatoid arthritis, Crohn’s disease, and Castleman’s disease. Transgenic mice lacking IL-6 expression were completely protected against collagen-induced arthritis, and Tumor Necrosis Factor (TNF-alpha) induces synovial cells to produce IL-6 and their proliferation. However, there is still some controversies regarding the unique proinflammatory activity of IL-6. Some studies have demonstrated that IL-6 and TNF-alpha may have an opposite effect in synovial cultured cells since IL-6 could represent a negative loop for TNF-alpha induced synovitis. However, phase III studies of rheumatoid arthritis patients treated with anti IL-6 receptor (tocilizumab) indicate an acceptable safety profile relative to the clinical benefit. AIM OF THE STUDY In this review, we summarized the rationale and the main evidence regarding the therapeutic benefit of blocking IL-6 activity in rheumatoid arthritis.

The role of cytokines in inflammatory response after total knee arthroplasty in patients with rheumatoid arthritis

2007 ◽  
Vol 28 (7) ◽  
pp. 667-671 ◽  
Author(s):  
B. Lisowska ◽  
W. Maśliński ◽  
P. Małdyk ◽  
J. Ząbek ◽  
E. Baranowska
Keyword(s):  
Rheumatoid Arthritis ◽  
Total Knee Arthroplasty ◽  
Inflammatory Response ◽  
Knee Arthroplasty ◽  
Total Knee

scholarly journals Digestive Inflammation: Role of Proteolytic Dysregulation

2021 ◽  
Vol 22 (6) ◽  
pp. 2817
Author(s):  
Vincent Mariaule ◽  
Aicha Kriaa ◽  
Souha Soussou ◽  
Soufien Rhimi ◽  
Houda Boudaya ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Side Effects ◽  
Inflammatory Response ◽  
Serine Proteases ◽  
Matrix Metalloproteases ◽  
Potential Contribution ◽  
Biological Processes ◽  
Bacterial Origin ◽  
Made In

Dysregulation of the proteolytic balance is often associated with diseases. Serine proteases and matrix metalloproteases are involved in a multitude of biological processes and notably in the inflammatory response. Within the framework of digestive inflammation, several studies have stressed the role of serine proteases and matrix metalloproteases (MMPs) as key actors in its pathogenesis and pointed to the unbalance between these proteases and their respective inhibitors. Substantial efforts have been made in developing new inhibitors, some of which have reached clinical trial phases, notwithstanding that unwanted side effects remain a major issue. However, studies on the proteolytic imbalance and inhibitors conception are directed toward host serine/MMPs proteases revealing a hitherto overlooked factor, the potential contribution of their bacterial counterpart. In this review, we highlight the role of proteolytic imbalance in human digestive inflammation focusing on serine proteases and MMPs and their respective inhibitors considering both host and bacterial origin.

scholarly journals METTL3 Promotes Activation and Inflammation of FLSs Through the NF-κB Signaling Pathway in Rheumatoid Arthritis

2021 ◽  
Vol 8 ◽  
Author(s):  
Wen Shi ◽  
Yan Zheng ◽  
Shuai Luo ◽  
Xiaofeng Li ◽  
Yilong Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Vital Role ◽  
Experimental Results ◽  
Invasion And Migration ◽  
Crucial Component ◽  
Synovial Tissues ◽  
And Migration

Rheumatoid arthritis (RA), a common autoimmune disease, is extremely damaging to human health. Fibroblast-like synoviocytes (FLSs) have a vital role in the occurrence and development of RA. Methyltransferase-like 3 (METTL3), which is a crucial component of the N6-methyladenosine (m6A) methyltransferase complex, is involved in the progression of many diseases. In this study, we explored the role of METTL3 in the inflammatory response and proliferation, invasion, and migration of FLSs. We used human RA synovial tissues and the adjuvant-induced arthritis (AIA) animal model of RA. Experimental results revealed that METTL3 expression was significantly upregulated in human RA synovial tissues and in the rat AIA model. METTL3 knockdown suppressed interleukin (IL)-6, matrix metalloproteinase (MMP)-3, and MMP-9 levels in human RA-FLSs and rat AIA-FLSs. In contrast, they were increased by METTL3 overexpression. Additionally, we found that, in FLSs, METTL3 may activate the nuclear factor (NF)-κB signaling pathway. The experimental results showed that METTL3 may promote FLS activation and inflammatory response via the NF-κB signaling pathway.

Dysregulation of synovial fibroblasts in rheumatoid arthritis

2020 ◽  
pp. 55-64
Author(s):  
Thomas Crowley ◽  
Jason D. Turner ◽  
Andrew Filer ◽  
Andy Clark ◽  
Chris Buckley
Keyword(s):  
Rheumatoid Arthritis ◽  
Extracellular Matrix ◽  
Immune System ◽  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Stromal Cells ◽  
Synovial Fibroblasts ◽  
Traditional Role ◽  
Level Of Involvement

Fibroblasts are ubiquitous stromal cells, with populations found in all organs. The traditional role of fibroblasts was thought to be mainly structural; making and modifying extracellular matrix. Taken together the ability of fibroblasts to produce and respond to many factors involved in the immune system indicates the degree to which they are involved in orchestrating the inflammatory response in rheumatoid arthritis (RA). This level of involvement demonstrates the importance of fibroblasts in inflammation and indicates the shift from transient to chronic inflammation in RA could be facilitated in part by synovial fibroblasts. This chapter explores the role of fibroblasts in RA.

Role of endotoxin in grain dust-induced lung inflammation in mice

1996 ◽  
Vol 270 (6) ◽  
pp. L1052-L1059 ◽  
Author(s):  
P. J. Jagielo ◽  
P. S. Thorne ◽  
J. A. Kern ◽  
T. J. Quinn ◽  
D. A. Schwartz
Keyword(s):  
Inflammatory Response ◽  
Membrane Filtration ◽  
Polymyxin B ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Endotoxin Activity ◽  
Grain Dust

To investigate the role of endotoxin in grain dust-induced airway inflammation, we reduced the endotoxin activity from extracts of corn dust (CDE), using three distinct methods, and determined the effect of endotoxin activity on the in vitro and in vivo inflammatory response to CDE. Escherichia coli lipopolysaccharide solution (LPS) and CDE solution were separated into > 100-kDa and < 100-kDa fractions by ultracentrifugation. Endotoxin activity was predominantly present in the > 100-kDa fractions of the LPS and CDE solutions. Charged-membrane filtration of the > 100-kDa fractions of LPS and CDE resulted in the reduction of endotoxin activity by 99.9 and 80%, respectively. Treatment of the > 100-kDa fractions of LPS and CDE with polymyxin B-coated beads reduced the endotoxin activity by 96 and 89%, respectively. The untreated > 100-kDa fractions of LPS and CDE caused significantly greater (P < 0.01) release of tumor necrosis factor-alpha (TNF-alpha) from THP-1 cells in vitro compared with its respective < 100-kDa fraction or either of the treated (charged filter or polymyxin B) > 100-kDa fractions. Similarly, mice exposed to either of the untreated > 100-kDa fractions of LPS or CDE by inhalation developed significantly greater (P < 0.01) concentrations of lavage neutrophils and TNF-alpha in the lavage fluid compared with mice exposed to the respective < 100-kDa fraction or either of the treated > 100-kDa fractions. These results indicate that endotoxin is primarily responsible for the in vitro and in vivo inflammatory response to CDE.

P3790Anti TNF alpha treatment restores endothelial dysfunction in rheumatoid arthritis mice: role of LOX-1 and arginase

2018 ◽  
Vol 39 (suppl_1) ◽  
Author(s):  
A Akhmedov ◽  
M Crucet ◽  
N R Bonetti ◽  
C Ospelt ◽  
S Briand ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Dysfunction ◽  
Tnf Alpha

scholarly journals CD109 regulates the inflammatory response and is required for the pathogenesis of rheumatoid arthritis

2019 ◽  
Vol 78 (12) ◽  
pp. 1632-1641 ◽  
Author(s):  
Guanhua Song ◽  
Tingting Feng ◽  
Ru Zhao ◽  
Qiqi Lu ◽  
Yutao Diao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Response ◽  
Osteoclast Differentiation ◽  
Small Interfering Rnas ◽  
Inflammatory Stimuli ◽  
Synovial Tissues ◽  
Factor Α ◽  
Fibroblast Like Synoviocytes

ObjectiveThe aim of this study was to investigate the role of CD109 in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and to evaluate its potential as a therapeutic target.MethodsCD109 expression was examined in synovial tissues and FLSs from RA patients and collagen-induced arthritis (CIA) model mice. CD109-deficient mice were developed to evaluate the severity of CIA. Small interfering RNAs and a neutralising antibody against CD109 (anti-CD109) were designed for functional or treatment studies in RA FLSs and CIA.ResultsCD109 was found to be abundantly expressed in the synovial tissues from RA patients and CIA mice. CD109 expression in RA FLSs was upregulated by inflammatory stimuli, such as interleukin-1β and tumour necrosis factor-α. Silencing of CD109 or anti-CD109 treatment reduced proinflammatory factor production, cell migration, invasion, chemoattractive potential and osteoclast differentiation, thereby reducing the deleterious inflammatory response of RA FLSs in vitro. Mice lacking CD109 were protected against arthritis in the CIA model. Anti-CD109 treatment prevented the onset and ameliorated the severity of CIA lesions.ConclusionOur study uncovers an antiarthritic role for CD109 and suggests that CD109 inhibition might serve as a promising novel therapeutic strategy for RA.

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