A novel PPAR response element in the murine iNOS promoter

Crosby, Meredith E.; Svenson, John L.; Gilkeson, Gary S.; Nowling, Tamara K.

doi:10.1016/j.molimm.2004.12.009

Cited by 44 publications

(32 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, NF-B is involved in the upregulation and PPAR␥ is involved in the downregulation of many inflammatory genes, and PPAR␥ is also important in lipid and glucose metabolism. Others have reported that treatment with a PPAR␥ agonist improves insulin resistance and yields beneficial effects in controlling atherosclerosis (6). Therefore, our study suggests that rifampin administration may have unfavorable effects in patients with chronic inflammatory diseases and glucose or lipid metabolism disorders.…”

Section: Discussionmentioning

confidence: 63%

See 1 more Smart Citation

Roles of NF-κB Activation and Peroxisome Proliferator-Activated Receptor Gamma Inhibition in the Effect of Rifampin on Inducible Nitric Oxide Synthase Transcription in Human Lung Epithelial Cells

Yuhas

Berent²,

Cohen

et al. 2009

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Rifampin (rifampicin), an important antibiotic agent and a major drug used for the treatment of tuberculosis, exerts immunomodulatory effects. Previous studies have found that rifampin increases inducible nitric oxide (NO) synthase (iNOS) expression and NO production. The present study investigated the potential mechanism(s) underlying these actions. The incubation of human lung epithelial A549 cells with a cytokine mix (interleukin-1␤, tumor necrosis factor alpha, and gamma interferon) induced the expression of iNOS mRNA. The addition of rifampin increased the iNOS level by 1.9 ؎ 0.3-fold at a dose of 10 g/ml (P < 0.01) and by 4.0 ؎ 0.3-fold at a dose of 50 g/ml (P < 0.001). Rifampin treatment also affected the transcription factors that regulate iNOS mRNA: there was an increased and prolonged degradation of the inhibitory subunit of NF-B, a corresponding increase in the level of cytokine-induced DNA binding of NF-B (2.1 ؎ 0.2-fold), and a decrease in the level of expression of peroxisome proliferator-activated receptor gamma (PPAR␥). Specifically, the level of PPAR␥ expression dropped by 15% in response to cytokine stimulation and by an additional 40% when rifampin was added (P < 0.001). Rifampin had no effect on the activation of mitogen-activated protein kinases or the signal transducer and transcription activator (STAT-1). In conclusion, rifampin augments NO production by upregulating iNOS mRNA. It also increases the level of NF-B activation and decreases the level of PPAR␥ expression. The increases in the levels of NF-B activation and NO production probably contribute to the therapeutic effects of rifampin. However, given the role of NF-B in upregulating many inflammatory genes and the roles of PPAR␥ in downregulating inflammatory genes and in lipid and glucose metabolism, these findings have implications for potential adverse effects of rifampin in patients with chronic inflammatory diseases and glucose or lipid disorders.

show abstract

Section: Discussionmentioning

confidence: 63%

“…Hence, the rifampin-induced activation of NF-B may be associated with the decrease in the level of PPAR␥ expression. Recently, a novel PPRE was identified in the murine iNOS promoter that binds to PPAR␥ (6). The PPRE contributed to negative iNOS expression in response to inflammatory stimuli.…”

Section: Discussionmentioning

confidence: 99%

Roles of NF-κB Activation and Peroxisome Proliferator-Activated Receptor Gamma Inhibition in the Effect of Rifampin on Inducible Nitric Oxide Synthase Transcription in Human Lung Epithelial Cells

Yuhas

Berent²,

Cohen

et al. 2009

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…As mentioned in the introduction, iNOS is essential for the IS-limiting effects of statins (2,49,71) since iNOS is needed for the activation of COX2 (2,6,34,71) and cPLA 2 (65) by S-nitrosylation. Several investigators have suggested that ciglitazone (14), rosiglitazone (15,16), and Pio (15,36) reduce iNOS expression and activity in various experimental models. The present study shows that in contrast to statins, Pio did not augment iNOS expression; moreover, Pio limited IS in iNOS Ϫ/Ϫ mice as it did in the WT mice, whereas statins do not (49,71), emphasizing the fact that the activating pathways of myocardial protection by statins and Pio are different.…”

Section: Role Of Inosmentioning

confidence: 99%

Pioglitazone protects the myocardium against ischemia-reperfusion injury in eNOS and iNOS knockout mice

Ye¹,

Lin²,

Manickavasagam³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Ye Y, Lin Y, Manickavasagam S, Perez-Polo JR, Tieu BC, Birnbaum Y. Pioglitazone protects the myocardium against ischemia-reperfusion injury in eNOS and iNOS knockout mice. Am J Physiol Heart Circ Physiol 295: H2436 -H2446, 2008. First published October 17, 2008 doi:10.1152/ajpheart.00690.2008.-Endothelial nitric oxide synthase (eNOS) activation with subsequent inducible NOS (iNOS), cytosolic phospholipase A2 (cPLA2), and cyclooxygenase-2 (COX2) activation is essential to statin inhibition of myocardial infarct size (IS). In the rat, the peroxisome proliferator-activated receptor-␥ agonist pioglitazone (Pio) limits IS, upregulates and activates cPLA 2 and COX2, and increases myocardial 6-keto-PGF1␣ levels without activating eNOS and iNOS. We asked whether Pio also limits IS in eNOS Ϫ/Ϫ and iNOS Ϫ/Ϫ mice. Male C57BL/6 wild-type (WT), eNOS Ϫ/Ϫ , and iNOS Ϫ/Ϫ mice received 10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 Pio (Pioϩ) or water alone (PioϪ) for 3 days. Mice underwent 30 min coronary artery occlusion and 4 h reperfusion, or hearts were harvested and subjected to ELISA and immunoblotting. As a result, Pio reduced IS in the WT (15.4 Ϯ 1.4% vs. 39.0 Ϯ 1.1%; P Ͻ 0.001), as well as in the eNOS Ϫ/Ϫ (32.0 Ϯ 1.6% vs. 44.2 Ϯ 1.9%; P Ͻ 0.001) and iNOS Ϫ/Ϫ (18.0 Ϯ 1.2% vs. 45.5 Ϯ 2.3%; P Ͻ 0.001) mice. The protective effect of Pio in eNOS Ϫ/Ϫ mice was smaller than in the WT (P Ͻ 0.001) and iNOS Ϫ/Ϫ (P Ͻ 0.001) mice. Pio increased myocardial Ser633 and Ser1177 phosphorylated eNOS levels in the WT and iNOS Ϫ/Ϫ mice. iNOS was undetectable in all six groups. Pio increased cPLA 2, COX2, and PGI2 synthase levels in the WT, as well as in the eNOS Ϫ/Ϫ and iNOS Ϫ/Ϫ , mice. Pio increased the myocardial 6-keto-PGF 1␣ levels and cPLA2 and COX2 activity in the WT, eNOS Ϫ/Ϫ , and iNOS Ϫ/Ϫ mice. In conclusion, the myocardial protective effect of Pio is iNOS independent and may be only partially dependent on eNOS. Because eNOS activity decreases with age, diabetes, and advanced atherosclerosis, this effect may be relevant in a clinical setting and should be further characterized. endothelial nitric oxide synthase; inducible nitric oxide synthase; peroxisome proliferator-activated receptor-␥ PROTECTION AGAINST ischemia-reperfusion injury may have a potential benefit in three distinct clinical situations: 1) limiting reperfusion injury in patients presenting with ST-elevation acute myocardial infarction before undergoing reperfusion therapy; 2) short-to intermediate-term treatment before elective procedures that may pose a risk for myocardial ischemia, such as cardiac or noncardiac surgery or percutaneous coronary interventions; and 3) long-term treatment in patients with established coronary artery disease to minimize the damage from an effort-induced ischemia or a potential future myocardial infarction. In the present study we studied whether the myocardial protection effects of intermediate-term pretreatment with pioglitazone (Pio) is dependent on nitric oxide (NO) synthases (NOSs), using a model that may be relevant to the second option mentioned above....

show abstract

“…20 Moreover, others have reported that thiazolidinediones suppress iNOS expression. [23][24][25] Thus, alteration of COX-2 by S-nitrosylation of a cysteine residue(s) may explain the mechanism by which ATV augments 15-epi-LXA 4 production but probably does not explain how PIO alters COX-2.…”

Section: · Dmentioning

confidence: 99%

Augmentation of Myocardial Production of 15-Epi-Lipoxin-A ₄ by Pioglitazone and Atorvastatin in the Rat

et al. 2006

View full text Add to dashboard Cite

Background-Both statins and thiazolidinediones have antiinflammatory properties. However, the exact mechanisms underlying these effects are unknown. We investigated whether atorvastatin (ATV) and pioglitazone (PIO) increase the myocardial content of lipoxin-A 4 and 15(R)-epi-lipoxin-A 4 (15-epi-LXA 4 ), both arachidonic acid products with strong antiinflammatory properties. Methods and Results-In experiment 1, rats received 3-day pretreatment with water; PIO 2, 5, or 10 mg · kg Ϫ1 · d Ϫ1 ; ATV 2, 5, or 10 mg · kg Ϫ1 · d

show abstract

A novel PPAR response element in the murine iNOS promoter

Cited by 44 publications

References 27 publications

Roles of NF-κB Activation and Peroxisome Proliferator-Activated Receptor Gamma Inhibition in the Effect of Rifampin on Inducible Nitric Oxide Synthase Transcription in Human Lung Epithelial Cells

Roles of NF-κB Activation and Peroxisome Proliferator-Activated Receptor Gamma Inhibition in the Effect of Rifampin on Inducible Nitric Oxide Synthase Transcription in Human Lung Epithelial Cells

Pioglitazone protects the myocardium against ischemia-reperfusion injury in eNOS and iNOS knockout mice

Augmentation of Myocardial Production of 15-Epi-Lipoxin-A ₄ by Pioglitazone and Atorvastatin in the Rat

Contact Info

Product

Resources

About

A novel PPAR response element in the murine iNOS promoter

Cited by 44 publications

References 27 publications

Roles of NF-κB Activation and Peroxisome Proliferator-Activated Receptor Gamma Inhibition in the Effect of Rifampin on Inducible Nitric Oxide Synthase Transcription in Human Lung Epithelial Cells

Roles of NF-κB Activation and Peroxisome Proliferator-Activated Receptor Gamma Inhibition in the Effect of Rifampin on Inducible Nitric Oxide Synthase Transcription in Human Lung Epithelial Cells

Pioglitazone protects the myocardium against ischemia-reperfusion injury in eNOS and iNOS knockout mice

Augmentation of Myocardial Production of 15-Epi-Lipoxin-A 4 by Pioglitazone and Atorvastatin in the Rat

Contact Info

Product

Resources

About

Augmentation of Myocardial Production of 15-Epi-Lipoxin-A ₄ by Pioglitazone and Atorvastatin in the Rat