Neutrophils in rheumatoid arthritis: More than simple final effectors

Cascão, Rita; Rosário, H S; Souto-Carneiro, Margarida; Fonseca, João Eurico

doi:10.1016/j.autrev.2009.12.013

Cited by 203 publications

(187 citation statements)

References 38 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…In addition to macrophages, neutrophils are implicated in both the onset and progression of arthritic disease, particularly in the process of joint degradation (37,38). To analyze the infiltration of neutrophils, the joints of the CIA mice were stained with antineutrophil Ab.…”

Section: Sb1578 Treatment Prevents Macrophage and Neutrophil Infiltramentioning

confidence: 99%

SB1578, a Novel Inhibitor of JAK2, FLT3, and c-Fms for the Treatment of Rheumatoid Arthritis

Madan¹,

Goh²,

Hart³

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

SB1578 is a novel, orally bioavailable JAK2 inhibitor with specificity for JAK2 within the JAK family and also potent activity against FLT3 and c-Fms. These three tyrosine kinases play a pivotal role in activation of pathways that underlie the pathogenesis of rheumatoid arthritis. SB1578 blocks the activation of these kinases and their downstream signaling in pertinent cells, leading to inhibition of pathological cellular responses. The biochemical and cellular activities of SB1578 translate into its high efficacy in two rodent models of arthritis. SB1578 not only prevents the onset of arthritis but is also potent in treating established disease in collagen-induced arthritis mice with beneficial effects on histopathological parameters of bone resorption and cartilage damage. SB1578 abrogates the inflammatory response and prevents the infiltration of macrophages and neutrophils into affected joints. It also leads to inhibition of Ag-presenting dendritic cells and inhibits the autoimmune component of the disease. In summary, SB1578 has a unique kinase spectrum, and its pharmacological profile provides a strong rationale for the ongoing clinical development in autoimmune diseases.

show abstract

Section: Sb1578 Treatment Prevents Macrophage and Neutrophil Infiltramentioning

confidence: 99%

SB1578, a Novel Inhibitor of JAK2, FLT3, and c-Fms for the Treatment of Rheumatoid Arthritis

Madan¹,

Goh²,

Hart³

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Diversos estudos têm destacado a contribuição de neutrófilos na fisiopatologia das primeiras fases desta doença (Cascao et al, 2010;Kundu et al, 2012). Os neutrófilos são os leucócitos mais abundantes presentes no fluido sinovial de pacientes com AR, sendo que a mobilização dessas células é mediada por diversas citocinas (Amulic et al, 2012;Carlos et al, 2014).…”

Section: Discussionunclassified

“…É caracterizada principalmente por hiperplasia sinovial, grandes infiltrados celulares, concentrações elevadas de citocinas pró-inflamatórias, destruição das articulações e manifestações extra-articulares que levam à dor, perda de função e redução na qualidade de vida (Cascao et al, 2010;Nemeth;Mocsai, 2012;Bardoel et al, 2014).…”

Section: Doença Inflamatória Com Envolvimento De Neutrófilos: Artriteunclassified

“…Embora a etiopatogenia desta condição não seja totalmente conhecida, é sabido que os PMNs estão envolvidos nos mecanismos que impulsionam o início da AR (Cascao et al, 2010 (Bardoel et al, 2014).…”

Section: Doença Inflamatória Com Envolvimento De Neutrófilos: Artriteunclassified

“…Diante do exposto, uma abordagem atraente para o tratamento de AR é a intervenção nas atividades dos PMNs de modo a modular a produção e/ou a liberação excessiva das ERO e do conteúdo citotóxico dos grânulos, sem alterar as funções de defesa destas células contra os patógenos invasores (Cascao et al, 2010). Para isso, existe uma busca contínua por reguladores das funções efetoras desta célula, para que novos fármacos, com atividades anti-inflamatória e antioxidante, sejam produzidos.…”

Section: Doença Inflamatória Com Envolvimento De Neutrófilos: Artriteunclassified

See 2 more Smart Citations

O extrato etanólico das folhas de Baccharis dracunculifolia (Asteraceae) modula funções efetoras de neutrófilos: um promissor agente fitoterápico para o tratamento de processos inflamatórios mediados por estas células

Rinhel¹

View full text Add to dashboard Cite

RibeirãoNeutrophils are phagocytic immune cells mobilized primarily to fight against infections. These cells are capable to kill microorganisms through degranulation, which leads to the release of antimicrobial molecules, and production of reactive oxygen species. Although neutrophil recruitment is essential for host protection, excessive activation of these cells culminates in intense discharge of cytotoxic molecules to the extracellular milieu, which can elicit the development of and/or aggravate the clinical condition in autoimmune and inflammatory diseases such as rheumatoid arthritis. Modulation of the effector functions of neutrophils is a possible therapeutic approach to treat these diseases. Previous studies have shown that the ethanolic extract of Baccharis dracunculifolia leaves (EEBd) has a great therapeutic potential due to its significant antioxidant effect towards the oxidative metabolism of neutrophils. To continue investigating the anti-inflammatory and/or immunomodulatory action of such extract, the first part of the present work examined its modulator effect on three important effector functions of human neutrophils that mediate recognition and clearance of pathogens -phagocytosis, degranulation, and microbial killing -and on the activity of lysosomal enzymes. EEBd inhibited the oxidative metabolism of neutrophils without affecting their defense ability, depending on the extract concentration used. To propose possible chemical markers for the biological effects of the extract, the second part of this study evaluated the antioxidant activity of seven compounds isolated from EEBd -caffeic acid, coumaric acid, ferulic acid, cinnamic acid, aromadendrin-4'-methyl ether, isosakuranetin, and hispidulin -towards the oxidative metabolism of neutrophils. The results pointed to caffeic acid as a potential chemical marker for this biological activity. The third part of this investigation aimed to improve the bioavailability and favor the therapeutic use of the natural products studied. EEBd and caffeic acid were incorporated into liposomal carrier systems. The incorporation of both samples into liposomes did not alter their antioxidant activity towards neutrophils, as compared with their respective free forms. Finally, this study examined the therapeutic effect of EEBd and caffeic acid, both in the free form and incorporated into liposomes, in an animal model of arthritis. The free samples markedly improved the joint inflammatory parameters: they reduced edema and migration of total cells and neutrophils, and slightly lowered the levels of the inflammatory cytokines tumor necrosis factor  and interleukin 6 and 1 (TNF-, IL-6, and IL-1, respectively). In addition, incorporation of EEBd and caffeic acid into liposomes can help to reduce their concentrations required to achieve the desired therapeutic effect. Based on the set of results obtained in this study, we conclude that EEBd has a great potential to become a therapeutic adjuvant in the treatment of neutrophil-mediated inflammatory diseases, and that...

show abstract

Biomimetic and Bioinspired Intervention Strategies for the Treatment of Rheumatoid Arthritis

Han

Pang

2021

Adv Funct Materials

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) affects the joints and extra-articular organs and poses a significant health care problem in the modern era. Although current standard treatment modalities successfully control RA flares, no curative treatment modality for RA has been developed. Nanomedicines have addressed the drug side effects and limited efficacy of RA treatment. However, synthetic nanoparticles (NPs) can be toxic and induce immune responses in vivo, posing a risk of further RA progression. Biomimetic nanodrug delivery systems have the potential to improve the biocompatibility of synthetic NPs and the stability and targeting of pharmaceuticals in vivo. For many immune-related diseases with a complex pathogenesis and that involve a large number of different cell types, biomimetic nanodelivery systems can reduce the immunogenicity of NPs. Furthermore, some bioinspired strategies can mimic certain components of the pathological process, allowing for a more precise drug delivery and effective disease control via the carriers. This article highlights recent research on biomimetic nanodelivery systems for the treatment of RA and categorizes the design methodologies for various targets and carriers.

show abstract

Neutrophils in rheumatoid arthritis: More than simple final effectors

Cited by 203 publications

References 38 publications

SB1578, a Novel Inhibitor of JAK2, FLT3, and c-Fms for the Treatment of Rheumatoid Arthritis

SB1578, a Novel Inhibitor of JAK2, FLT3, and c-Fms for the Treatment of Rheumatoid Arthritis

O extrato etanólico das folhas de Baccharis dracunculifolia (Asteraceae) modula funções efetoras de neutrófilos: um promissor agente fitoterápico para o tratamento de processos inflamatórios mediados por estas células

Biomimetic and Bioinspired Intervention Strategies for the Treatment of Rheumatoid Arthritis

Contact Info

Product

Resources

About