Digoxin ameliorates autoimmune arthritis via suppression of Th17 differentiation

Lee, Jennifer; Baek, Seung-Ye; Lee, Jae‐Seon; Lee, Juhyun; Lee, Dong Gun; Park, Mi-Kyung; Cho, Mi‐La; Park, Sung-Hwan; Kwok, Seung‐Ki

doi:10.1016/j.intimp.2015.03.017

Cited by 56 publications

(26 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Additionally, a study conducted by Cascão et al (Cascão et al, 2012) using celastrol, a plantderived triterpene known to improve autoimmune arthritis by suppressing Th17 differentiation, showed it to be more effective in reducing edema than digoxin (Lee et al, 2015). Celastrol was able to suppress arthritis scores in the early and late phase, while digoxin was only effective when administered in the early stage.…”

Section: Anti-edematogenic Effectsmentioning

confidence: 99%

“…In this context, alterations in the inflammatory mediator's cascades play a pivotal role in the pathophysiological processes underlying inflammation and tissue destruction in arthritic diseases. Some studies indicate that the beneficial pharmacological properties of terpenes against arthritis phenomena are related to modulation of several intracellular signaling pathway proteins, such as RANKL (Wang et al, 2016), NFκB (Z. M. , the MAPK family (Chen et al, 2015), COX-2 (Lee et al, 2015), iNOS (Lee et al, 2015, PGE-2 (Li et al, 2009), matrix metalloproteinases (Liu et al, 2015, Nanjundaiah et al, 2012, MPO (Zhang et al, 2017) and c-FOS (Kang et al, 2008). Terpenes can provoke the activation or inhibition of these molecules or pathways reducing the diseases progression.…”

Section: Modulation Of Signaling Pathways Associated With Inflammatormentioning

confidence: 99%

See 1 more Smart Citation

Terpenes as possible drugs for the mitigation of arthritic symptoms – A systematic review

et al. 2019

View full text Add to dashboard Cite

Background Arthritis is a syndrome associated with exacerbated inflammation, joint destruction and chronic pain and disability. Chronic treatment of arthritis is associated with several side effects and high abandonment. Therefore, there has been an ongoing search for alternative treatments to overcome these problems. Purpose Natural products, which are already widely used for their biological, cosmetic and pharmacotechnic properties, are a possible source for new drugs. Terpenes, a large class of organic compounds produced mainly by plants and trees, are a promising natural product and have already been shown to be effective in treating chronic pain, particularly of an inflammatory origin. Study Design and Methods This review identifies the main terpenes with anti-arthritic activity reported in the last 10 years. A survey was conducted between December 2017 and June 2018 in the PUBMED, SCOPUS and Science Direct databases using combinations of the descriptors terpenes, arthritis and inflammation. Results The results showed that terpenes have promising biological effects in relation to the treatment of arthritis, with the 24 terpenes identified in our survey being effective in the modulation of inflammatory mediators important to the physiopathology of arthritis, such as IL-6, IL-17, TNF-α, NFκB, and COX-2, among others. It is important to note that most of the studies used animal models, which limits, at least in part, the direct translation to humans of the experimental evidence produced by the studies. Conclusion Together, our finds suggest that terpenes can modulate the immuno-regulatory and destructive tissue events that underlie the clinical presentation and the progression of arthritis and are worthy of further clinical investigation.

show abstract

Section: Anti-edematogenic Effectsmentioning

confidence: 99%

Section: Modulation Of Signaling Pathways Associated With Inflammatormentioning

confidence: 99%

Terpenes as possible drugs for the mitigation of arthritic symptoms – A systematic review

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Since WT and IL-32␥Tg mouse BMDMs produced NO at similar levels, we reasoned that the increased L. infantum antigen-specific NO production observed in IL-32␥Tg mouse spleen cells was secondary to the increased Th1/Th17 cytokine levels induced by IL-32␥. Splenic cells from 30-day-infected WT and IL-32␥Tg mice were then incubated with total antigen of L. infantum in the absence or presence of neutralizing antibody to IFN-␥ or to TNF-␣ or a pharmacological inhibitor of Th17 cell differentiation and IL-17A production in vivo and in vitro (digoxin) (36,37). Neutralization of IFN-␥ or Th17/IL-17A inhibition significantly reduced the antigen-specific NO production by IL-32␥Tg mouse splenic cells.…”

Section: Fig 2 Il-32␥mentioning

confidence: 99%

Human Interleukin-32γ Plays a Protective Role in an Experimental Model of Visceral Leishmaniasis in Mice

et al. 2018

View full text Add to dashboard Cite

Visceral leishmaniasis (VL) is a chronic parasitic disease caused by in the Americas. During VL, several proinflammatory cytokines are produced in spleen, liver, and bone marrow. However, the role of interleukin-32 (IL-32) has not been explored in this disease. IL-32 can induce production of proinflammatory cytokines in innate immune cells and polarize the adaptive immune response. Herein, we discovered that antigens induced expression of mRNA mainly for the IL-32γ isoform but also induced low levels of the IL-32β transcript in human peripheral blood mononuclear cells. Furthermore, infection of human IL-32γ transgenic mice (IL-32γTg mice) with promastigote forms increased IL-32γ expression in the spleen and liver. Interestingly, IL-32γTg mice harbored less parasitism in the spleen and liver than wild-type (WT) mice. In addition, IL-32γTg mice showed increased granuloma formation in the liver compared to WT mice. The protection against VL was associated with increased production of nitric oxide (NO), interferon gamma (IFN-γ), IL-17A, and tumor necrosis factor alpha by splenic cells restimulated with antigens. In parallel, there was an increase in the number of Th1 and Th17 T cells in the spleens of IL-32γTg mice infected with IL-32γ induction of IFN-γ and IL-17A expression was found to be essential for NO production by splenic cells of infected animals. These data indicate that IL-32γ potentiates the Th1/Th17 immune response during experimental VL, thus contributing to the control of infection.

show abstract

“…To overcome the limitations of CGs regarding their toxicity, the authors searched for chemical modifications of digoxin with a decreased affinity to the Na + -K + -ATPase and an augmented affinity to RORγt and identified the two compounds 20,22-dihydrodigoxin-21,23-diol and digoxin-21-salicylidene. Inspired by these important findings on the influence of CGs on T H 17 cells, the action of digoxin was tested in two further models of autoimmune diseases: Lee et al [37] provided evidence for both a preventive and therapeutic action of digoxin (2 and 5 mg/kg bodyweight) on collagen-induced arthritis in mice. Digoxin lowered the joint inflammation and reduced the expression of IL-17, IL-1β, IL-6, TNFα, and IL-21.…”

Section: Chronic Inflammatory Autoimmune Diseasesmentioning

confidence: 99%

New Knowledge About Old Drugs: The Anti-Inflammatory Properties of Cardiac Glycosides

2017

View full text Add to dashboard Cite

In the 19th century, cardio-active steroid glycosides, shortly cardiac glycosides, were scientifically established as drugs against heart failure. Their in vivo, cellular, and molecular actions as well as their predominant target, Na+-K+-ATPase, have been comprehensively investigated in the 20th century and the discovery of endogenous cardiac glycosides has fostered this research field. In the last years, however, results from clinical trials and meta-analyses have questioned their therapeutic value due to efficacy and safety issues. This has led to a considerable decline of their usage. Beyond the cardiovascular system, cardiac glycosides have been increasingly recognized as antitumor compounds and Na+-K+-ATPase has evolved into a promising drug target in oncology. A wealth of review articles exists that intensively discuss these topics. Surprisingly, the anti-inflammatory actions of cardiac glycosides, which were discovered in the 1960s, have so far hardly been perceived and have not yet been summarized. This review provides an overview of the in vivo and in vitro actions of cardiac glycosides on inflammatory processes and of the signaling mechanisms responsible for these effects: cardiac glycosides have been found to decrease inflammatory symptoms in different animal models of acute and chronic inflammation. Regarding the underlying mechanisms most research has focused on leukocytes. In these cells, cardiac glycosides primarily inhibit cell proliferation and the secretion of proinflammatory cytokines.

show abstract

Digoxin ameliorates autoimmune arthritis via suppression of Th17 differentiation

Cited by 56 publications

References 20 publications

Terpenes as possible drugs for the mitigation of arthritic symptoms – A systematic review

Terpenes as possible drugs for the mitigation of arthritic symptoms – A systematic review

Human Interleukin-32γ Plays a Protective Role in an Experimental Model of Visceral Leishmaniasis in Mice

New Knowledge About Old Drugs: The Anti-Inflammatory Properties of Cardiac Glycosides

Contact Info

Product

Resources

About