Role of Peroxisome Proliferator-Activated Receptors in Inflammation Control.
Jihan Youssef,Mostafa Z. Badr +1 more
Reads0
Chats0
TLDR
The bulk of evidence suggests that all three PPAR subtypes, PPARα, δ, γ, play a significant role in controlling inflammatory responses.Abstract:
Peroxisome proliferator-activated receptors (PPARs) were discovered over a decade ago, and were classified as orphan members of the nuclear receptor superfamily. To date, three PPAR subtypes have been discovered and characterized (PPARα, β/δ, γ). Different PPAR subtypes have been shown to play crucial roles in important diseases and conditions such as obesity, diabetes, atherosclerosis, cancer, and fertility. Among the most studied roles of PPARs is their involvement in inflammatory processes. Numerous studies have revealed that agonists of PPARα and PPARγ exert anti-inflammatory effects both in vitro and in vivo. Using the carrageenan-induced paw edema model of inflammation, a recent study in our laboratories showed that these agonists hinder the initiation phase, but not the late phase of the inflammatory process. Furthermore, in the same experimental model, we recently also observed that activation of PPARδ exerted an anti-inflammatory effect. Despite the fact that exclusive dependence of these effects on PPARs has been questioned, the bulk of evidence suggests that all three PPAR subtypes, PPARα, δ, γ, play a significant role in controlling inflammatory responses. Whether these subtypes act via a common mechanism or are independent of each other remains to be elucidated. However, due to the intensity of research efforts in this area, it is anticipated that these efforts will result in the development of PPAR ligands as therapeutic agents for the treatment of inflammatory diseases.read more
Citations
More filters
Journal ArticleDOI
Peroxisome proliferator-activated receptors and inflammation.
TL;DR: Peroxisome proliferator-activated receptors ligands, in particular those of PPARalpha and PPARgamma, inhibit the activation of inflammatory gene expression and can negatively interfere with pro-inflammatory transcription factor signaling pathways in vascular and inflammatory cells.
Journal ArticleDOI
Receptor-independent actions of PPAR thiazolidinedione agonists: Is mitochondrial function the key?
Douglas L. Feinstein,Alessandra Spagnolo,Candan A Akar,Guy L. Weinberg,Patricia Murphy,Vitaliy Gavrilyuk,C. Dello Russo +6 more
TL;DR: Evidence that TZDs directly influence mitochondrial function, and attempts to reconcile how changes in mitochondrial function could contribute to other receptor-independent actions of these drugs are reviewed.
Journal ArticleDOI
Peroxisome proliferator-activated receptor-gamma agonist extends survival in transgenic mouse model of amyotrophic lateral sclerosis
TL;DR: Investigation of the therapeutic effect of pioglitazone in the G93A SOD1 transgenic mouse model of ALS suggests that the drug may have therapeutic potential for human ALS.
Journal ArticleDOI
Hydrogen Peroxide Probes Directed to Different Cellular Compartments
Mikalai Malinouski,You Zhou,Vsevolod V. Belousov,Dolph L. Hatfield,Vadim N. Gladyshev,Vadim N. Gladyshev +5 more
TL;DR: It is found that HyPer can be used as a valuable tool to monitor hydrogen peroxide generated in different cellular compartments, and the data show that hydrogen peroxy generated in one compartment could translocate to other compartments.
Journal ArticleDOI
Angiotensin II blockade: a strategy to slow ageing by protecting mitochondria?
TL;DR: The available data suggest that RAS blockade deserves further research efforts to establish its role as a potential tool to mitigate the growing problem of age-associated chronic disease.
References
More filters
Journal ArticleDOI
The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation
Mercedes Ricote,Andrew C. Li,Andrew C. Li,Timothy M. Willson,Carolyn J. Kelly,Christopher K. Glass +5 more
TL;DR: It is shown that PPAR-γ is markedly upregulated in activated macrophages and inhibits the expression of the inducible nitric oxide synthase, gelatinase B and scavenger receptor A genes in response to 15d-PGJ2 and synthetic PPar-γ ligands, suggesting that PPARS and locally produced prostaglandin D2 metabolites are involved in the regulation of inflammatory responses.
Journal ArticleDOI
Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators
Isabelle Issemann,Stephen Green +1 more
TL;DR: A member of the steroid hormone receptor superfamily of ligand-activated transcription factors is cloned that is activated by a diverse class of rodent hepatocarcinogens that causes proliferation of peroxisomes.
Journal ArticleDOI
Peroxisome proliferator-activated receptors: nuclear control of metabolism.
Béatrice Desvergne,Walter Wahli +1 more
TL;DR: This work has shown that direct expression of PPAR mRNAs in the absence of a specific carrier gene results in down-regulation in the activity of other PPARs, and these properties are consistent with those of a “spatially aggregating substance”.
Journal ArticleDOI
PPAR-γ agonists inhibit production of monocyte inflammatory cytokines
TL;DR: Inhibition of cytokine production may help to explain the incremental therapeutic benefit of NSAIDs observed in the treatment of rheumatoid arthritis at plasma drug concentrations substantially higher than are required to inhibit prostaglandin G/H synthase (cyclooxygenase).
Journal ArticleDOI
The Mechanisms of Action of PPARs
Joel P. Berger,David E. Moller +1 more
TL;DR: The current state of knowledge regarding the molecular mechanisms of PPAR action and the involvement of the PPARs in the etiology and treatment of several chronic diseases is presented.
Related Papers (5)
PPAR-γ agonists inhibit production of monocyte inflammatory cytokines
Peroxisome proliferator-activated receptors: nuclear control of metabolism.
Béatrice Desvergne,Walter Wahli +1 more
Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators
Isabelle Issemann,Stephen Green +1 more