Paquinimod reduces skin fibrosis in tight skin 1 mice, an experimental model of systemic sclerosis

Stenström, Martin; Nyhlén, Helén; Törngren, Marie; Liberg, David; Sparre, Birgitta; Tuvesson, Helén; Eriksson, Helena; Leanderson, Tomas

doi:10.1016/j.jdermsci.2016.04.006

Cited by 38 publications

(26 citation statements)

References 39 publications

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“…23 Several studies have suggested that Paquinimod binds Mrp14 protein and disrupts its binding to the proinflammatory receptors (RAGE) and TLR4. A novel report by Yang et al 21 demonstrated that Mrp8/14 upregulated TNF-α and IL-6 expression levels and activated the phosphorylation of NF-κB P65 in mouse macrophages.…”

Section: Platelet-neutrophil Interaction Upregulates Tlr4/myd88/nf-mentioning

confidence: 99%

Platelet‐neutrophil interaction aggravates vascular inﬂammation and promotes the progression of atherosclerosis by activating the TLR4/NF‐κB pathway

Liang

Xiu

Liu

et al. 2018

J of Cellular Biochemistry

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Platelet‐neutrophil interaction is well known for its role in inflammatory diseases; however, its biological role in atherosclerosis (AS) progression remains unclear. Human peripheral blood neutrophils were obtained to compare toll‐like receptor 4 (TLR4), tumor necrosis factor α (TNF‐α), interleukin (IL)‐1β and myeloid‐related proteins 8/14 (Mrp8/14) levels in 22 AS patients with those in 18 healthy controls using quantitative real‐time polymerase chain reaction (qRT‐PCR) and enzyme‐linked immunosorbent assay (ELISA). Meanwhile, mouse marrow neutrophils subjected to different treatment were collected for the ELISA assay, cell apoptosis, and Western blot analysis. Normal diet or high‐fat diet ApoE−/− mice with or without administration of Mrp8/14 antagonist paquinimod were used for plasma collection to measure total cholesterol, triglycerides, low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol, TNF‐α, IL‐1β, Mrp8/14, TLR4, and nuclear factor (NF)‐κB p65 levels. The results showed that Mrp8/14 and TLR4‐mediated inflammatory pathway was activated in neutrophils of AS patients. In vitro experiments demonstrated that platelet‐neutrophil interaction promoted the Mrp8/14 release and inhibited neutrophil apoptosis via P‐selectin. Furthermore, platelet‐neutrophil interaction upregulated TLR4/myeloid differentiation factor 88/NF‐κB pathway. Conversely, Mrp8/14/TLR4/NF‐κB interference alleviated AS progression. In conclusion, Mrp8/14/TLR4/NF‐κB activated by platelet‐neutrophil interaction is an important inflammatory signaling pathway for AS pathogenesis.

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Section: Platelet-neutrophil Interaction Upregulates Tlr4/myd88/nf-mentioning

confidence: 99%

Platelet‐neutrophil interaction aggravates vascular inﬂammation and promotes the progression of atherosclerosis by activating the TLR4/NF‐κB pathway

Liang

Xiu

Liu

et al. 2018

J of Cellular Biochemistry

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“…The potential mechanism of Pirfenidone is inhibiting the nuclear accumulation of intracellular proteins SMAD2/3 to regulate TGF-β signaling (Choi et al, 2012 ). Other approved inhibitor drugs include Ruxolitinib for bone marrow fibrosis (Wilkins et al, 2013 ), Paquinimod for SSc (Stenstrom et al, 2016 ), and Pentoxifylline (Okunieff et al, 2004 ) combined with vitamin E (Jacobson et al, 2013 ).…”

Section: Drugs and Targets In Fibrosismentioning

confidence: 99%

Drugs and Targets in Fibrosis

Zhu

Wang

et al. 2017

Front. Pharmacol.

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Fibrosis contributes to the development of many diseases and many target molecules are involved in fibrosis. Currently, the majority of fibrosis treatment strategies are limited to specific diseases or organs. However, accumulating evidence demonstrates great similarities among fibroproliferative diseases, and more and more drugs are proved to be effective anti-fibrotic therapies across different diseases and organs. Here we comprehensively review the current knowledge on the pathological mechanisms of fibrosis, and divide factors mediating fibrosis progression into extracellular and intracellular groups. Furthermore, we systematically summarize both single and multiple component drugs that target fibrosis. Future directions of fibrosis drug discovery are also proposed.

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“…Blockade of S100A8/9 binding to its receptor by administration of Paquinimod was beneficial. Specific inhibition of S100A8/9 by Paquinimod reduced inflammation and pathology under various disease conditions, including leukocyte recruitment during sterile inflammation, experimental systemic sclerosis, and experimental osteoarthritis ( 102 – 105 ). Therefore, MDSC may represent the S100A8/9-driven connection that links massive neutrophil influx to impaired Th1 immune responses and memory phenotypes thereof.…”

Section: Controlling Th1-supressing Immune Cell Subpopulationsmentioning

confidence: 99%

Strategies to Improve Vaccine Efficacy against Tuberculosis by Targeting Innate Immunity

et al. 2017

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The global tuberculosis epidemic is the most common cause of death after infectious disease worldwide. Increasing numbers of infections with multi- and extensively drug-resistant variants of the Mycobacterium tuberculosis complex, resistant even to newly discovered and last resort antibiotics, highlight the urgent need for an efficient vaccine. The protective efficacy to pulmonary tuberculosis in adults of the only currently available vaccine, M. bovis BCG, is unsatisfactory and geographically diverse. More importantly, recent clinical studies on new vaccine candidates did not prove to be better than BCG, yet. Here, we propose and discuss novel strategies to improve efficacy of existing anti-tuberculosis vaccines. Modulation of innate immune responses upon vaccination already provided promising results in animal models of tuberculosis. For instance, neutrophils have been shown to influence vaccine efficacy, both, positively and negatively, and stimulate specific antibody secretion. Modulating immune regulatory properties after vaccination such as induction of different types of innate immune cell death, myeloid-derived suppressor or regulatory T cells, production of anti-inflammatory cytokines such as IL-10 may have beneficial effects on protection efficacy. Incorporation of lipid antigens presented via CD1 molecules to T cells have been discussed as a way to enhance vaccine efficacy. Finally, concepts of dendritic cell-based immunotherapies or training the innate immune memory may be exploitable for future vaccination strategies against tuberculosis. In this review, we put a spotlight on host immune networks as potential targets to boost protection by old and new tuberculosis vaccines.

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Paquinimod reduces skin fibrosis in tight skin 1 mice, an experimental model of systemic sclerosis

Abstract: Paquinimod reduces skin fibrosis in an experimental model of SSc, and this effect correlates with local and systemic effects on the immune system.

Cited by 38 publications

References 39 publications

Platelet‐neutrophil interaction aggravates vascular inﬂammation and promotes the progression of atherosclerosis by activating the TLR4/NF‐κB pathway

Platelet‐neutrophil interaction aggravates vascular inﬂammation and promotes the progression of atherosclerosis by activating the TLR4/NF‐κB pathway

Drugs and Targets in Fibrosis

Strategies to Improve Vaccine Efficacy against Tuberculosis by Targeting Innate Immunity

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