scholarly journals Emerging role of leptin in joint inflammation and destruction

2021 ◽  
pp. 1-8
Author(s):  
Haruka Tsuchiya ◽  
Keishi Fujio
Keyword(s):  
Joint Inflammation

scholarly journals Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis

2006 ◽  
Vol 203 (2) ◽  
pp. 325-335 ◽  
Author(s):  
Tetsuya Honda ◽  
Eri Segi-Nishida ◽  
Yoshiki Miyachi ◽  
Shuh Narumiya
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Joint Inflammation ◽  
Synovial Fibroblasts ◽  
The Other ◽  
Receptor Subtype ◽  
Significant Suppression ◽  
Wild Type ◽  
Collagen Induced Arthritis

Prostaglandin (PG)I2 (prostacyclin [PGI]) and PGE2 are abundantly present in the synovial fluid of rheumatoid arthritis (RA) patients. Although the role of PGE2 in RA has been well studied, how much PGI2 contributes to RA is little known. To examine this issue, we backcrossed mice lacking the PGI receptor (IP) to the DBA/1J strain and subjected them to collagen-induced arthritis (CIA). IP-deficient (IP−/−) mice exhibited significant reduction in arthritic scores compared with wild-type (WT) mice, despite anti-collagen antibody production and complement activation similar to WT mice. IP−/− mice also showed significant reduction in contents of proinflammatory cytokines, such as interleukin (IL)-6 in arthritic paws. Consistently, the addition of an IP agonist to cultured synovial fibroblasts significantly enhanced IL-6 production and induced expression of other arthritis-related genes. On the other hand, loss or inhibition of each PGE receptor subtype alone did not affect elicitation of inflammation in CIA. However, a partial but significant suppression of CIA was achieved by the combined inhibition of EP2 and EP4. Our results show significant roles of both PGI2-IP and PGE2-EP2/EP4 signaling in the development of CIA, and suggest that inhibition of PGE2 synthesis alone may not be sufficient for suppression of RA symptoms.

scholarly journals AB0056 TNFR2 PROMOTES INFLAMMATORY PROGRAMS IN FIBROBLAST-LIKE SYNOVIOCYTES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1060.2-1060
Author(s):  
T. Suto ◽  
K. Von Dalwigk ◽  
A. Platzer ◽  
B. Niederreiter ◽  
T. M. Karonitsch
Keyword(s):  
Joint Destruction ◽  
Joint Inflammation ◽  
Rna Seq ◽  
Synovial Joint ◽  
Interferon Stimulated Genes ◽  
Transcriptional Changes ◽  
Proinflammatory Gene ◽  
Proinflammatory Gene Expression ◽  
Fibroblast Like Synoviocytes

Background:TNF-mediated fibroblast-like synoviocyte (FLS) activation is important for inflammation and joint destruction in rheumatoid arthritis (RA). The role of TNF-receptor 1 (TNFR1) in FLS activation has thoroughly been characterized. The functions of TNFR2 are, however, largely unknown.Objectives:To investigate the contribution of TNFR2 to the TNF-mediated activation of FLS.Methods:RA-FLS were transfected with TNFR2-targeting siRNA pools and transcriptional changes were determined by RNA-seq. QPCR, ELISA and immunoblotting were used to confirm the RNA-seq results and to gain insights into the pathways that regulate TNFR2-mediated changes in FLS.Results:TNF stimulation of FLS resulted in a strong upregulation of proinflammatory cytokines, chemokines, tissue-degrading enzymes and other genes that are associated with synovial inflammation in RA. Silencing of TNFR2 markedly diminished the TNF-response of RA-FLS. Especially, “interferon”-stimulated-genes (ISGs) including putative master regulators of joint inflammation, such as the CXCR3 chemokines CXCL9, CXCL10 and CXCL11 were affected by the knockdown of TNFR2. Consistently, immunoblots showed that TNFR2 was required for the TNF-induced phosphorylation of the transcription factor STAT1, which is known to mediate the transcription of ISGs, such as CXCR3 chemokines.Conclusion:TNFR2 regulates proinflammatory gene expression in RA-FLS via STAT1 and thereby contributes to the detrimental effects of TNF in synovial joint inflammation.Disclosure of Interests:None declared

scholarly journals Differential attenuation of β2 integrin–dependent and –independent neutrophil migration by Ly6G ligation

2019 ◽  
Vol 3 (3) ◽  
pp. 256-267 ◽  
Author(s):  
Pierre Cunin ◽  
Pui Y. Lee ◽  
Edy Kim ◽  
Angela B. Schmider ◽  
Nathalie Cloutier ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Neutrophil Migration ◽  
Surface Protein ◽  
Joint Inflammation ◽  
Selective Inhibition ◽  
Β2 Integrin ◽  
Β2 Integrins ◽  
Neutrophil Surface

Abstract Antibody ligation of the murine neutrophil surface protein Ly6G disrupts neutrophil migration in some contexts but not others. We tested whether this variability reflected divergent dependence of neutrophil migration on β2 integrins, adhesion molecules that interact with Ly6G at the neutrophil surface. In integrin-dependent murine arthritis, Ly6G ligation attenuated joint inflammation, even though mice lacking Ly6G altogether developed arthritis normally. By contrast, Ly6G ligation had no impact on integrin-independent neutrophil migration into inflamed lung. In peritoneum, the role of β2 integrins varied with stimulus, proving dispensable for neutrophil entry in Escherichia coli peritonitis but contributory in interleukin 1 (IL-1)–mediated sterile peritonitis. Correspondingly, Ly6G ligation attenuated only IL-1 peritonitis, disrupting the molecular association between integrins and Ly6G and inducing cell-intrinsic blockade restricted to integrin-dependent migration. Consistent with this observation, Ly6G ligation impaired integrin-mediated postadhesion strengthening for neutrophils arresting on activated cremaster endothelium in vivo. Together, these findings identify selective inhibition of integrin-mediated neutrophil emigration through Ly6G ligation, highlighting the marked site and stimulus specificity of β2 integrin dependence in neutrophil migration.

scholarly journals Role of Hydrogen Sulfide in the Pathology of Inflammation

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Madhav Bhatia
Keyword(s):  
Hydrogen Sulfide ◽  
Joint Inflammation ◽  
Chronic Obstructive ◽  
Therapeutic Approaches ◽  
Obstructive Pulmonary Disease ◽  
The Past ◽  
Inflammatory Conditions ◽  
Incurable Disease ◽  
Active Research

Hydrogen sulfide (H2S) is a well-known toxic gas that is synthesized in the human body from the amino acids cystathionine, homocysteine, and cysteine by the action of at least two distinct enzymes: cystathionine-γ-lyase and cystathionine-β-synthase. In the past few years, H2S has emerged as a novel and increasingly important biological mediator. Imbalances in H2S have also been shown to be associated with various disease conditions. However, defining the precise pathophysiology of H2S is proving to be a complex challenge. Recent research in our laboratory has shown H2S as a novel mediator of inflammation and work in several groups worldwide is currently focused on determining the role of H2S in inflammation. H2S has been implicated in different inflammatory conditions, such as acute pancreatitis, sepsis, joint inflammation, and chronic obstructive pulmonary disease (COPD). Active research on the role of H2S in inflammation will unravel the pathophysiology of its actions in inflammatory conditions and may help develop novel therapeutic approaches for several, as yet incurable, disease conditions.

scholarly journals The tissue specific role of SirT1 in joint inflammation and anabolic cartilage gene expression

2015 ◽  
Vol 23 ◽  
pp. A33
Author(s):  
P.K. Sacitharan ◽  
J. Zarebska ◽  
A. Chanalaris ◽  
G. Bou Gharios ◽  
E. J ◽  
...  
Keyword(s):  
Gene Expression ◽  
Joint Inflammation ◽  
Specific Role ◽  
Tissue Specific

scholarly journals The Role of Intracellular Organisms in the Pathogenesis of Inflammatory Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Animesh Singh ◽  
Sarah Karrar
Keyword(s):  
Rheumatoid Arthritis ◽  
Reactive Arthritis ◽  
Inflammatory Arthritis ◽  
Molecular Mimicry ◽  
Joint Inflammation ◽  
Joint Space ◽  
Low Grade ◽  
Infectious Episode ◽  
Persistent Symptoms

Inflammatory arthritis is a condition which is characterised by recurrent episodes of joint pain and swelling. It encompasses a spectrum of disorders ranging from rheumatoid arthritis to ankylosing spondylitis. In these conditions, for reasons that are poorly understood, the immune system raises an inflammatory response within the joint space. In some cases, autoantigens have been identified (e.g., anticitrullinated peptides in rheumatoid arthritis), but the absence of these, in the seronegative arthritides, for example, raises question as to the underlying pathogenesis. Interest has, therefore, turned to host-pathogen interactions and whether aberrant immune responses to these could explain the development of arthritis. This has been most widely studied in reactive arthritis (ReA), where an infectious episode precedes the development of the joint symptoms. In this review, we present the evidence for the role of host-bacterial interactions in the pathogenesis of joint inflammation with particular emphasis on ReA. We discuss a range of possible mechanisms including molecular mimicry, persistent low grade infections, and abnormal host responses to common bacterial causes of reactive arthritis as well as discussing some of the clinical challenges that we face in making the diagnosis and in treatment of persistent symptoms.

scholarly journals A roadmap to target interleukin-6 in osteoarthritis

Rheumatology ◽  
2020 ◽  
Vol 59 (10) ◽  
pp. 2681-2694
Author(s):  
Renske Wiegertjes ◽  
Fons A J van de Loo ◽  
Esmeralda N Blaney Davidson
Keyword(s):  
Synovial Fluid ◽  
Disease Incidence ◽  
Joint Inflammation ◽  
Protective Role ◽  
Future Perspective ◽  
Current Evidence ◽  
Joint Pathology ◽  
Matrix Degrading Enzymes ◽  
Review Current

Abstract Joint inflammation is present in the majority of OA patients and pro-inflammatory mediators, such as IL-6, are actively involved in disease progression. Increased levels of IL-6 in serum or synovial fluid from OA patients correlate with disease incidence and severity, with IL-6 playing a pivotal role in the development of cartilage pathology, e.g. via induction of matrix-degrading enzymes. However, IL-6 also increases expression of anti-catabolic factors, suggesting a protective role. Until now, this dual role of IL-6 is incompletely understood and may be caused by differential effects of IL-6 classic vs trans-signalling. Here, we review current evidence regarding the role of IL-6 classic- and trans-signalling in local joint pathology of cartilage, synovium and bone. Furthermore, we discuss targeting of IL-6 in experimental OA models and provide future perspective for OA treatment by evaluating currently available IL-6 targeting strategies.

scholarly journals Contrasting role of NLRP12 in autoinflammation: evidence from a case report and mouse models

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e001824
Author(s):  
Dan Lévy ◽  
Alexandre Mariotte ◽  
Aurore DeCauwer ◽  
Cecile Macquin ◽  
Angélique Pichot ◽  
...  
Keyword(s):  
Mouse Models ◽  
Ex Vivo ◽  
Joint Inflammation ◽  
Autoinflammatory Syndrome ◽  
Her Family ◽  
Whole Exome ◽  
Urate Crystals

ObjectiveTo explore at the molecular level the phenotype of a patient suffering an autoinflammatory syndrome which was diagnosed as familial cold autoinflammatory syndrome type 2 (FCAS-2). To explore the functions of Nlrp12 in inflammation using mouse models.MethodsWhole exome sequencing and Nlrp12 targeted resequencing were performed on DNA isolated from the patient and her family members. In vivo and ex vivo models of inflammation (urate crystals-dependent acute joint inflammation and urate crystals-induced peritonitis) were analysed in Nlrp12-deficient and Nlrp12-competent mice.ResultsA rare missense NLRP12 variant (c.857C>T, p.P286L) was identified in the patient and her healthy relatives. Nlrp12-deficient mice exhibit reduced systemic inflammation and neutrophilic infiltration.ConclusionNlrp12 mediates proinflammatory functions in mice. In humans, the identification of Nlrp12 variants must be cautiously interpreted depending on clinical and paraclinical data to diagnose FCAS-2.

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