Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms

Straus, Daniel S.; Glass, Christopher K.

doi:10.1016/j.it.2007.09.003

Cited by 479 publications

(430 citation statements)

References 83 publications

Supporting

Mentioning

397

Contrasting

Unclassified

Order By: Relevance

“…2C). This result might reflect inhibition of IL-1β gene transcription by PPARγ, which is strongly activated in adipocytes (reviewed in [38]), and is responsible for the resolution of inflammation in other cell types, by NF-κB-dependent and independent mechanisms [39,40].…”

Section: Resultsmentioning

confidence: 99%

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

et al. 2011

View full text Add to dashboard Cite

1 IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodelingsuggested that expression of IL-33, in contrast to that of IL-1β, is not repressed by PPARγ, likely explaining why IL-33, but not IL-1β, is expressed in adipocytes. The IL-33 receptor ST2L is not constitutively expressed in human bone marrow stromal cells, osteoblasts or CD14-positive monocytes, and IL-33 has no effect on these cells. In addition, although ST2L mRNA is induced by TNF-α and IL-1β in bone marrow stromal cells, IL-33 has the same effects as TNF-α and IL-1β, and, therefore, the biological activity of IL-33 may be redundant in this system. In agreement with this hypothesis, MC3T3-E1 osteoblast-like cells constitutively express ST2L mRNA, and in these cells IL-33 and TNF-α/IL-1β similarly decrease osteocalcin RNA levels in these cells. In conclusion, our results suggest that IL-33 has no direct effects on normal bone remodeling.

show abstract

Section: Resultsmentioning

confidence: 99%

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

et al. 2011

View full text Add to dashboard Cite

show abstract

“…40 Rosiglitazone improved both collagen-induced arthritis 41 and adjuvant-induced arthritis in mice. 42 Genistein-treated and collagen II immunized mice showed milder inflammation and joint destruction.…”

Section: Discussionmentioning

confidence: 99%

Genistein induces adipogenesis but inhibits leptin induction in human synovial fibroblasts

Relić

Zeddou

Desoroux

et al. 2009

Laboratory Investigation

View full text Add to dashboard Cite

It was shown recently that synovial fibroblast transformation into adipocytes reduced the expression of interleukin-6 (IL-6) and IL-8. However, the synovial fibroblast adipogenesis was inhibited in inflammatory conditions induced by the tumor necrosis factor-a (TNF-a). Furthermore, adipogenesis is often accompanied by leptin production, a proinflammatory adipokine in rheumatic diseases. In this study, we tested the phytohormone genistein for adipogenic and anti-inflammatory properties on human synovial fibroblasts. Results showed that genistein was able to transform synovial fibroblasts into adipocytes that expressed perilipin-A and produced adiponectin, but not leptin. Furthermore, genistein enhanced glucocorticoid-mediated synovial fibroblast adipogenesis and, in parallel, downregulated glucocorticoid-induced leptin and leptin receptor. Endogenous and TNF-a-induced expressions of IL-6, IL-8, p38, p65 and C/EBP-b were also downregulated by genistein, showing its anti-inflammatory properties. Peroxisome proliferatoractivated receptor-g (PPAR-g) agonist, rosiglitazone, had a synergic effect on genistein-induced adipogenesis, whereas the non-active tyrosine kinase inhibitor, daidzein, had a significantly inferior adipogenic activity than genistein. The Janus kinase-2 tyrosine kinase inhibitor, AG 490, mimicked the anti-leptin effect of genistein. These results showed that genistein-induced adipogenesis involves PPAR-g induction and tyrosine kinase inhibition. In conclusion, genistein, alone or coupled with glucocorticoids, have both adipogenic and anti-inflammatory effects on synovial fibroblasts.

show abstract

“…Several anti-inflammatory mechanisms of PPAR agonists have now been documented, including suppression of adhesion molecule expression, chemokine secretion and TLR ( fig. 4) [196]. reduced expression of PGC-1a [197].…”

Section: Ppar Agonistsmentioning

confidence: 99%

Systemic manifestations and comorbidities of COPD

Barnes¹,

Celli²

2009

European Respiratory Journal

1,465

1,113

View full text Add to dashboard Cite

Increasing evidence indicates that chronic obstructive pulmonary disease (COPD) is a complex disease involving more than airflow obstruction. Airflow obstruction has profound effects on cardiac function and gas exchange with systemic consequences. In addition, as COPD results from inflammation and/or alterations in repair mechanisms, the ''spill-over'' of inflammatory mediators into the circulation may result in important systemic manifestations of the disease, such as skeletal muscle wasting and cachexia. Systemic inflammation may also initiate or worsen comorbid diseases, such as ischaemic heart disease, heart failure, osteoporosis, normocytic anaemia, lung cancer, depression and diabetes. Comorbid diseases potentiate the morbidity of COPD, leading to increased hospitalisations, mortality and healthcare costs. Comorbidities complicate the management of COPD and need to be evaluated carefully. Current therapies for comorbid diseases, such as statins and peroxisome proliferator-activated receptor-agonists, may provide unexpected benefits for COPD patients. Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities. However, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future. Another approach is the reversal of corticosteroid resistance, for example with effective antioxidants. More research is needed on COPD comorbidities and their treatment.

show abstract

Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms

Cited by 479 publications

References 83 publications

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

Genistein induces adipogenesis but inhibits leptin induction in human synovial fibroblasts

Systemic manifestations and comorbidities of COPD

Contact Info

Product

Resources

About