Activation of the peroxisome proliferator–activated receptor α pathway potentiates interleukin‐1 receptor antagonist production in cytokine‐treated chondrocytes

François, Mathias; Richette, Pascal; Tsagris, Lydia; Fitting, Catherine; May, Cédric Le; Benallaoua, Mourad; Tahiri, Khadija; Corvol, Marie-Thérèse

doi:10.1002/art.21728

Cited by 39 publications

(49 citation statements)

References 40 publications

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“…This promoter construct was active in HepG2 cells, as previously demonstrated by several groups (24,27). IL-1␤/IL-6 treatment for 24 h led to a 6.5-fold activation of this promoter construct (Fig.…”

Section: Resultssupporting

confidence: 49%

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Interleukin-1 Receptor Antagonist Induction as an Additional Mechanism for Liver Receptor Homolog-1 to Negatively Regulate the Hepatic Acute Phase Response

Venteclef

Delerive

2007

Journal of Biological Chemistry

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The liver receptor homolog-1 (LRH-1) is an orphan nuclear receptor believed to play a key role in bile acid metabolism, cholesterol homeostasis, and intestinal cell crypt renewal. LRH-1 has recently been reported to negatively regulate the hepatic acute phase response by antagonizing, at least in part, the CCAAT/enhancer-binding protein signaling pathway. The liver receptor homolog-1 (LRH-1 2 ; NR5A2) is a member of the nuclear receptor superfamily (1). Nuclear receptors have central roles in nearly every aspect of development and adult physiology. LRH-1 is the mammalian homolog of the Drosophila Fushi Tarazu F1 receptor (FTZ-F1; NR5A3) and, similar to FTZ-F1, binds its cognate target sequence (5Ј-(Py)CAAGG(Py)-C(Pu)-3Ј) as a monomer (2). It is highly expressed in the ovary, liver, intestine, and pancreas (2-4). Several groups have recently shown by x-ray crystallography that the human LRH-1 ligand binding pocket can bind various phospholipids, including phosphoinositides and phosphatidylethanolamine, linking phospholipid metabolism to gene transcription (5-8). LRH-1 is involved in the regulation of the expression of transcription factors implicated in embryonic development, such as Oct4 and the hepatic nuclear factors HNF-3␤, HNF4␣, and HNF1␣ (9, 10). Recently, LRH-1 was shown to regulate estrogen production through the control of aromatase (CYP19) gene transcription in ovarian and adipose tissue (10, 11) and adiponectin in adipocytes (12). Furthermore, LRH-1 has recently been reported to be involved in intestinal crypt cell renewal by coactivating ␤-catenin on the cyclin D1 promoter (13). In addition, LRH-1 is believed to be a key player in cholesterol homeostasis (1). LRH-1 is known to play a pivotal role in the transcriptional regulation of CYP7A1, the rate-limiting enzyme of the bile acid biosynthetic pathway (3) and CYP8B1, the oxysterol 12␣-hydroxylase required for cholic acid production (14). Moreover, LRH-1 has been reported to regulate the expression of APO A1 (15), ABCG5/ABCG8 (16), CETP (17), SR-B1 (4), and the carboxyl ester lipase (18), thereby implicating this receptor in high density lipoprotein remodeling and cholesterol transport.Recently, we have been shown that LRH-1 is a negative regulator of the hepatic acute phase response (APR) (19). Ectopic expression of LRH-1 using adenovirus resulted in the inhibition of IL-1␤-and IL-6-mediated induction of acute phase gene expression, such as haptoglobin (HP), serum amyloid A, and C-reactive protein in cultured hepatocytes. In addition, LRH-1 partial deficiency led to an exacerbated inflammatory response in vitro and in vivo, indicating that LRH-1 is a physiological modulator of hepatic APR. Moreover, molecular studies revealed that LRH-1 negatively interferes with the development of the APR by, at least in part, antagonizing C/EBP transcriptional activity (19).To better understand the role of LRH-1 in the control of APR, we compared LRH-1-mediated APR gene regulation in HepG2 cells after a short or prolonged cytokine exposure. We found that the inter...

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Section: Resultssupporting

confidence: 49%

“…5). PPAR␣ (peroxisome proliferator-activated receptor ␣) was recently reported to regulate IL-1RA expression in chondrocytes by a similar mechanism (27). Indeed, PPAR␣-mediated IL-1RA gene promoter activation required the activation of both NFB and C/EBP transcription factors (27).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1 Receptor Antagonist Induction as an Additional Mechanism for Liver Receptor Homolog-1 to Negatively Regulate the Hepatic Acute Phase Response

Venteclef

Delerive

2007

Journal of Biological Chemistry

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“…In fact, the expression pattern of IL-33 was more similar to that of IL-1 receptor antagonist, the natural inhibitor of IL-1β, which is also expressed in non-inflammatory bone [41] and in adipocytes (our unpublished data and [42]). It will be interesting to examine whether the expression of IL-33, like that of IL-1Ra, is also controlled by PPARα [43,44] and PPARβ/δ [45].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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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.

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“…The suppression of oxidative stress by PGC-1a activation could already be shown to be neuroprotective (88,136,137). PGC-1a function also appears to suppress the production of inflammatory mediators as cytokines, which will minimize overall tissue damage (138,139).…”

Section: Pgc-1a Induced Mitochondrial Biogenesis As a Potential Theramentioning

confidence: 99%

PGC‐1α activation as a therapeutic approach in mitochondrial disease

Wenz

2009

IUBMB Life

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SummaryMitochondria play a central role in cellular homeostasis. Hence, mitochondrial dysfunction resulting in impaired ATP supply is detrimental to cell viability and causes severe and often fatal disorders. Current treatment of these mitochondrial disorders is limited and mostly addresses the symptoms, but not the deficiency itself. Recent work in cell and animal models of mitochondrial disease shows that increased mitochondrial biogenesis can boost residual OXPHOS capacity and thereby prevent the bioenergetic crisis. In animal models, this strategy results in increased health and lifespan. Here, I review which mitochondrial processes are affected in known mitochondrial disorders and discuss why PGC-1a mediated mitochondrial biogenesis offers a promising venue for treatment of mitochondrial disorders.

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Activation of the peroxisome proliferator–activated receptor α pathway potentiates interleukin‐1 receptor antagonist production in cytokine‐treated chondrocytes

Cited by 39 publications

References 40 publications

Interleukin-1 Receptor Antagonist Induction as an Additional Mechanism for Liver Receptor Homolog-1 to Negatively Regulate the Hepatic Acute Phase Response

Interleukin-1 Receptor Antagonist Induction as an Additional Mechanism for Liver Receptor Homolog-1 to Negatively Regulate the Hepatic Acute Phase Response

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

PGC‐1α activation as a therapeutic approach in mitochondrial disease

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